September 2024 – Page 8 – 1stOncology™: Cancer Intelligence Service

Novel combination of TALVEY® (talquetamab-tgvs) and TECVAYLI® (teclistamab-cqyv) suggests high response rates and durable responses in triple-class refractory patients with relapsed or refractory multiple myeloma, including those with extramedullary disease

On September 27, 2024 Johnson & Johnson (NYSE: JNJ) reported updated results from the investigational Phase 1b RedirecTT-1 study evaluating the first-ever bispecific antibody combination of TALVEY (talquetamab-tgvs), the first and only FDA-approved bispecific targeting GPRC5D, and TECVAYLI (teclistamab-cqyv), the first FDA-approved BCMA-directed bispecific therapy, showing high response rates and durable responses, with a consistent safety profile to each monotherapy, in patients with relapsed or refractory multiple myeloma (RRMM) who were triple-class exposed, including those with extramedullary disease (Press release, Johnson & Johnson, SEP 27, 2024, View Source;302261023.html [SID1234646902]). These data were featured in an oral presentation at the 2024 International Myeloma Society Annual Meeting (Abstract # OA – 03).

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"As multiple myeloma progresses, it becomes more difficult to treat, especially in patients with extramedullary disease, which spreads beyond the bone marrow and typically becomes resistant to standard therapies," said Yael Cohen, M.D., Head of Myeloma Unit, Hematology Institute, Tel Aviv Sourasky Medical Center, Israel, and principal study investigator.* "These results reflect promising efficacy and a manageable safety profile for this combination of two first-in-class, innovative bispecific therapies and provide a potentially promising off-the-shelf option for patients with advanced multiple myeloma."

At data cutoff, 44 patients had been treated with the recommended phase 2 regimen (RP2R) of 0.8 mg/kg of TALVEY in combination with 3 mg/kg of TECVAYLI every other week, the overall response rate (ORR) was 79.5 percent, with a complete response or better (CR+) rate of 52.3 percent, an 18-month duration of response (DOR) of 85.9 percent, and an 18-month progression-free survival (PFS) rate of 69.8 percent with median follow-up of 18.2 months.1

Results from a subgroup analysis of patients with extramedullary disease (EMD; ≥1 bone-independent lesion of ≥2 cm), a patient population often facing limited treatment options, demonstrated meaningful ORR and DOR for bispecific antibody-based treatment. At the RP2R (n=18), results showed an ORR of 61.1 percent, with CR+ rate of 33.3 percent, an 18-month DOR of 81.8 percent, and an 18-month PFS rate of 52.9 percent in patients with EMD at median follow-up 13.6 months.1

The combination of TALVEY and TECVAYLI had a safety profile that was consistent with the known safety profiles of each agent as monotherapy. Cumulative incidence of Grade 3/4 infections was slightly higher than that seen with either agent as monotherapy but plateaued from six months, and non-hematologic adverse events were generally low grade, including taste (50 percent) and non-rash skin (56.8 percent) and nail (47.7 percent) AEs, with no discontinuations due to cytopenias.1

"TALVEY and TECVAYLI have already demonstrated powerful efficacy as standalone therapies as first-in-class bispecifics in the clinical and real-world settings," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Innovative Medicine at Johnson & Johnson. "We continue to research this innovative combination, as this study demonstrates both the efficacy and manageable safety profile of this combination, particularly in hard-to-treat patients such as those with EMD, as well as the combinability of TALVEY with other effective therapies."

Additional data underscoring the combinability of TALVEY from the TRIMM-2 study will also be presented at IMS. First results from the RedirecTT-1 study were presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

About RedirecTT
The RedirecTT-1 (NCT04586426) study is an ongoing Phase 1b dose escalation study of the combination of the bispecific T-cell redirection antibodies TALVEY and TECVAYLI in patients (n=208) with relapsed or refractory multiple myeloma. The primary objective is to identify the recommended Phase 2 regimen(s) (RP2R[s]) and schedule for the study treatment and to characterize the safety of the RP2R(s) for the study treatment. In part 1, patients will receive TALVEY and TECVAYLI with or without daratumumab in 28-day cycles following initial step-up doses. In part 2, patients will receive treatment doses (combination of TALVEY and TECVAYLI and daratumumab + TALVEY + TECVAYLI regimens) which will be determined by the recommended Phase 2 regimen (s) (RP2R[s]) of the study treatment identified in Part 1. In part 3, patients will receive TALVEY + TECVAYLI combination therapy, at the RP2R selected from Part 1 and Part 2.

About Multiple Myeloma
Multiple myeloma is a blood cancer affecting a type of white blood cell called plasma cells found in the bone marrow.2 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.3 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.4 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.5 People with multiple myeloma have a 5-year survival rate of 59.8 percent.6 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.7,8

About TALVEY
TALVEY (talquetamab-tgvs) received approval from the U.S. FDA in August 2023 as a first-in-class GPRC5D-targeting bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.8 Since FDA approval, 1,500 patients were treated with TALVEY. The European Commission (EC) granted conditional marketing authorization (CMA) of TALVEY (talquetamab-tgvs) in August 2023 as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.9

TALVEY is a bispecific T cell engaging antibody that binds to the CD3 receptor expressed on the surface of T cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target which is highly expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as some healthy tissues such as epithelial cells of the skin and tongue.

For more information, visit www.TALVEY.com.

About TECVAYLI

TECVAYLI (teclistamab-cqyv) received approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.2 The European Commission (EC) granted TECVAYLI conditional marketing authorization (CMA) in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months. TECVAYLI is a first-in-class, bispecific T cell engager antibody therapy that uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months.

For more information, visit www.TECVAYLI.com.

TALVEY IMPORTANT SAFETY INFORMATION

INDICATION AND USAGE

TALVEY (talquetamab-tgvs) is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY. Initiate TALVEY treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening or fatal reactions, can occur with TALVEY. Monitor patients for signs and symptoms of neurologic toxicity including ICANS during treatment. Withhold or discontinue TALVEY based on severity.

Because of the risk of CRS and neurologic toxicity, including ICANS, TALVEY is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS).

CONTRAINDICATIONS: None.

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome (CRS): TALVEY can cause cytokine release syndrome, including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 76% of patients who received TALVEY at the recommended dosages, with Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. CRS occurred in 33% of patients with step-up dose 3 in the biweekly dosing schedule (N=153). CRS occurred in 30% of patients with the first 0.4 mg/kg treatment dose and in 12% of patients treated with the first 0.8 mg/kg treatment dose. The CRS rate for both dosing schedules combined was less than 3% for each of the remaining doses in Cycle 1 and less than 3% cumulatively from Cycle 2 onward. The median time to onset of CRS was 27 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, and tachycardia. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).

Initiate therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of TALVEY in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY dose.

Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity, and consider further management per current practice guidelines. Withhold TALVEY until CRS resolves or permanently discontinue based on severity.

Neurologic Toxicity including ICANS: TALVEY can cause serious or life-threatening neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including fatal reactions. In the clinical trial, neurologic toxicity occurred in 55% of patients who received the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), and motor dysfunction (10%).

ICANS was reported in 9% of 265 patients where ICANS was collected and who received the recommended dosages. Recurrent ICANS occurred in 3% of patients. Most patients experienced ICANS following step-up dose 1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or the initial treatment dose of the weekly dosing schedule (2.6%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity; withhold or permanently discontinue TALVEY based on severity and consider further management per current practice guidelines. [see Dosage and Administration (2.5)].

Due to the potential for neurologic toxicity, patients receiving TALVEY are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule, and in the event of new onset of any neurological symptoms, until symptoms resolve.

TECVAYLI and TALVEY REMS: TALVEY is available only through a restricted program under a REMS, called the TECVAYLI and TALVEY REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Further information about the TECVAYLI and TALVEY REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064.

Oral Toxicity and Weight Loss: TALVEY can cause oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis. In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occurring in 2.1% of patients who received the recommended dosages. The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients.

TALVEY can cause weight loss. In the clinical trial, 62% of patients experienced weight loss of 5% or greater, regardless of having an oral toxicity, including 28% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss.

Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice, including consultation with a nutritionist. Monitor weight regularly during therapy. Evaluate clinically significant weight loss further. Withhold TALVEY or permanently discontinue based on severity.

Infections: TALVEY can cause infections, including life-threatening or fatal infections. Serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%), which included sepsis and COVID-19 (2.7%).

Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or consider permanently discontinuing TALVEY as recommended, based on severity.

Cytopenias: TALVEY can cause cytopenias, including neutropenia and thrombocytopenia. In the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 35% of patients, and Grade 3 or 4 decreased platelets occurred in 22% of patients who received TALVEY. The median time to onset for Grade 3 or 4 neutropenia was 22 (range: 1 to 312) days, and the median time to resolution to Grade 2 or lower was 8 (range: 1 to 79) days. The median time to onset for Grade 3 or 4 thrombocytopenia was 12 (range: 2 to 183) days, and the median time to resolution to Grade 2 or lower was 10 (range: 1 to 64) days. Monitor complete blood counts during treatment and withhold TALVEY as recommended, based on severity.

Skin Toxicity: TALVEY can cause serious skin reactions, including rash, maculo-papular rash, erythema, and erythematous rash. In the clinical trial, skin reactions occurred in 62% of patients, with grade 3 skin reactions in 0.3%. The median time to onset was 25 (range: 1 to 630) days. The median time to improvement to grade 1 or less was 33 days.

Monitor for skin toxicity, including rash progression. Consider early intervention and treatment to manage skin toxicity. Withhold TALVEY as recommended based on severity.

Hepatotoxicity: TALVEY can cause hepatotoxicity. Elevated ALT occurred in 33% of patients, with grade 3 or 4 ALT elevation occurring in 2.7%; elevated AST occurred in 31% of patients, with grade 3 or 4 AST elevation occurring in 3.3%. Grade 3 or 4 elevations of total bilirubin occurred in 0.3% of patients. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TALVEY or consider permanent discontinuation of TALVEY, based on severity [see Dosage and Administration (2.5)].

Embryo-Fetal Toxicity: Based on its mechanism of action, TALVEY may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TALVEY and for 3 months after the last dose.

Adverse Reactions: The most common adverse reactions (≥20%) are pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache.

The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.

Please read full Prescribing Information, including Boxed Warning, for TALVEY.

TECVAYLI IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently discontinue based on severity.

TECVAYLI is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS).

INDICATION AND USAGE

TECVAYLI (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome – TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).

Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI based on severity.

TECVAYLI is available only through a restricted program under a REMS.

Neurologic Toxicity including ICANS – TECVAYLI can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI.

In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

TECVAYLI is available only through a restricted program under a REMS.

TECVAYLI and TALVEY REMS – TECVAYLI is available only through a restricted program under a REMS called the TECVAYLI and TALVEY REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Hepatotoxicity – TECVAYLI can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Infections – TECVAYLI can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%. Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Monitor immunoglobulin levels during treatment with TECVAYLI and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Neutropenia – TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.

Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI based on severity.

Hypersensitivity and Other Administration Reactions – TECVAYLI can cause both systemic administration-related and local injection-site reactions. Systemic Reactions – In patients who received TECVAYLI at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions – In patients who received TECVAYLI at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Embryo-Fetal Toxicity – Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI.

AbbVie Submits Biologics License Application to the FDA for Telisotuzumab Vedotin (Teliso-V) in Previously Treated Non-Small Cell Lung Cancer

On September 27, 2024 AbbVie (NYSE: ABBV) reported submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for accelerated approval of telisotuzumab vedotin (Teliso-V) in adult patients with previously treated, locally advanced or metastatic epidermal growth factor receptor (EGFR) wild type, nonsquamous non-small cell lung cancer (NSCLC) with c-Met protein overexpression (Press release, AbbVie, SEP 27, 2024, View Source [SID1234646901]).

Approximately 85% of lung cancers are classified as NSCLC1 and despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths throughout the world.2 The c-Met protein is a receptor tyrosine kinase found to be overexpressed in approximately 25% of advanced EGFR wild type, nonsquamous NSCLC patients3 and is associated with a poor prognosis.4,5,6 Teliso-V is being evaluated within this patient population who currently have very limited treatment options.

"Patients with non-small cell lung cancer have unmet medical needs and oncologists are looking for new treatment options for these patients who unfortunately have a poor prognosis," said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie. "We are hopeful that Teliso-V will be a differentiated treatment for certain patients as we look to elevate the standards of care in oncology."

In December 2021, Teliso-V was granted Breakthrough Therapy Designation by the FDA. The BLA submission is supported by data from Phase 2 LUMINOSITY trial (Study M14-239), an ongoing study designed to characterize the safety and efficacy of Teliso-V in c-Met overexpressing NSCLC populations. Data from the LUMINOSITY study were recently presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) congress and topline data from this trial were shared in 2023. Teliso-V is being further evaluated as a monotherapy in patients with previously treated c-Met overexpressing NSCLC in the randomized Phase 3 confirmatory global study TeliMET NSCLC-01. Enrollment in the study is underway and continues across global clinical trial sites. Additional information on clinical trials for Teliso-V is available at www.clinicaltrials.gov.

About Telisotuzumab Vedotin (Teliso-V)
Teliso-V is an investigational, first-in-class, c-Met protein directed antibody-drug conjugate (ADC) designed to target c-Met overexpressing tumors. c-Met is a receptor tyrosine kinase that can be overexpressed in many solid tumors including NSCLC. Further information on clinical trials for Teliso-V is available at View Source Teliso-V is not approved by any health regulatory authority.

About the LUMINOSITY Trial
The LUMINOSITY trial (M14-239), is an ongoing Phase 2 study designed to identify the target NSCLC populations that overexpress c-Met best suited for Teliso-V monotherapy in the second-line or third-line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).

DARZALEX FASPRO®-based quadruplet regimen significantly improves minimal residual disease negativity for newly diagnosed multiple myeloma patients for whom transplant is not planned

On September 27, 2024 Johnson & Johnson (NYSE:JNJ) reported results from the Phase 3 CEPHEUS study demonstrating a significant clinical improvement with DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) in the treatment of patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible (TIE) or for whom transplant was not planned as initial therapy (transplant deferred) (Press release, Johnson & Johnson, SEP 27, 2024, View Source [SID1234646900]). The data showing significant improvement in minimal residual disease (MRD) negativity rate, progression-free survival (PFS) and complete response (CR) or better rate, were featured as a late-breaking oral presentation at the 2024 International Myeloma Society (IMS) Annual Meeting (Abstract #OA — 63).

CEPHEUS is an ongoing, multicenter, randomized, open-label, Phase 3 study evaluating the efficacy and safety of D-VRd compared to bortezomib, lenalidomide and dexamethasone (VRd) for NDMM patients for whom transplant was not planned as initial therapy (TIE or deferred). Results show that treatment with D-VRd resulted in deeper responses, including MRD-negativity, compared with VRd. At a median follow-up of 58.7 months, the primary endpoint was met, with overall MRD-negativity rate at a sensitivity of 10-5 (no cancer cells detected within 100,000 bone marrow cells) of 60.9 percent for patients receiving D-VRd and 39.4 percent for VRd (OR [odds ratio], 2.37; 95% confidence interval [CI], 1.58-3.55; P<0.0001). The proportion of patients achieving sustained MRD-negativity of ≥ 12 months almost doubled with D-VRd vs VRd (48.7 percent vs 26.3 percent; P<0.0001). The study also demonstrated that D-VRd significantly reduced the risk of progression or death by 43 percent (HR [hazard ratio], 0.57; 95% CI, 0.41-0.79; P<0.0005) vs VRd. The median PFS was not reached for D-VRd vs 52.6 months for VRd.1

"The CEPHEUS study results show that 60 percent of patients achieved MRD negativity, which is clinically important for physicians treating patients with multiple myeloma and, in general, a strong predictor of improved long-term outcomes, including progression free survival and overall survival," said Saad Z. Usmani, M.D., F.A.C.P., Chief, Myeloma Service, Memorial Sloan Kettering Cancer Center and study investigator.* "The subcutaneous daratumumab-based quadruplet regimen has compelling efficacy characterized by deep, durable responses and reduced risk of disease progression in the frontline population of patients not undergoing transplant, supporting the potential of this quadruplet to become a new regimen in this treatment setting."

The DARZALEX FASPRO-based quadruplet regimen, compared to VRd, also significantly increased the depth of response with higher rates of CR or better. The CR or better rate was 81.2 percent with D-VRd vs 61.6 percent with VRd (P<0.0001). Overall survival data are not yet mature. The overall safety profile of D-VRd was consistent with the known safety profiles for DARZALEX FASPRO and VRd. The most common (>10 percent) Grade 3/4 hematologic and non-hematologic adverse events with D-VRd vs VRd were neutropenia (44.2 percent vs 29.7 percent), thrombocytopenia (28.4 percent vs 20.0 percent), anemia (13.2 percent vs 11.8 percent), peripheral neuropathies (8.1 percent vs 8.2 percent), diarrhea (12.2 percent vs 9.2 percent), and COVID-19 (11.2 percent vs 4.6 percent).1

"Data from PERSEUS and now CEPHEUS add to the body of evidence illustrating how the DARZALEX FASPRO-based quadruplet regimen has the potential to be a foundational frontline therapy across all patient types during first-line treatment, regardless of transplant eligibility status," said Robin Carson, M.D., Global Head, Oncology, Innovative Medicine, Johnson & Johnson. "We look forward to continuing to advance this potential new quadruplet therapy and deliver on our commitment to transforming outcomes for people with multiple myeloma."

About the CEPHEUS Study
CEPHEUS (NCT03652064) is an ongoing, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd vs VRd in patients with newly diagnosed multiple myeloma for whom autologous stem cell transplant (ASCT) is not planned as initial therapy. The primary endpoint is minimal residual disease (MRD)-negativity rate at a 10-5 sensitivity threshold. Key secondary endpoints include overall complete response (CR) or better rate, progression-free survival (PFS), and sustained MRD-negative rate at 1 year. The trial has enrolled 396 patients in 13 countries.

About the PERSEUS Study
The PERSEUS study (NCT03710603) is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for autologous stem cell transplant (ASCT). Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm. The study is being conducted in 14 countries in Europe and Australia.

About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.3 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.4 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.5 People with multiple myeloma have a 5-year survival rate of 59.8 percent.5 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.6,7

About DARZALEX FASPRO
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.1 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

For more information, visit View Source

DARZALEX FASPRO INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation. 

WARNINGS AND PRECAUTIONS 

Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO. 

Systemic Reactions
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO.

Local Reactions
In this pooled safety population, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.

Neutropenia
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.

Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets. 

Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose. 

The combination of DARZALEX FASPRO with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy. 

Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. 

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO. Type and screen patients prior to starting DARZALEX FASPRO. 

Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein. 

ADVERSE REACTIONS
In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, peripheral edema, musculoskeletal pain, and rash.

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin. 

Please click here to read full Prescribing Information for DARZALEX FASPRO.

DARZALEX® (daratumumab)-based maintenance regimens show clinically meaningful deep and durable responses in transplant-eligible patients with newly diagnosed multiple myeloma

On September 27, 2024 Johnson & Johnson (NYSE: JNJ) reported data from three studies highlighting clinical efficacy of DARZALEX (daratumumab) and DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in maintenance regimens (Press release, Johnson & Johnson, SEP 27, 2024, View Source [SID1234646899]). Data from the Phase 3 AURIGA study show DARZALEX FASPRO plus lenalidomide (D-R) maintenance therapy following autologous stem cell transplant (ASCT) significantly increases MRD-negative conversion rates at 12 months compared to lenalidomide (R) maintenance alone in patients with newly diagnosed multiple myeloma (NDMM). DARZALEX FASPRO plus lenalidomide maintenance therapy also demonstrated a potential benefit in progression-free survival (PFS) with no new safety concerns.1 Data were featured in an oral presentation at the 2024 International Myeloma Society (IMS) Annual Meeting (Abstract #OA – 45).

"The significant improvement in MRD-negative conversion rates and the promising progression-free survival data suggest that this maintenance regimen has the potential to improve longer-term outcomes for patients with newly diagnosed multiple myeloma who are transplant-eligible," said Dr. Ashraf Badros, professor of medicine at the University of Maryland School of Medicine and Director of the Multiple Myeloma Service at the University of Maryland Greenebaum Comprehensive Cancer Center within University of Maryland Medical Center in Maryland.* "Combining DARZALEX FASPRO with lenalidomide in the maintenance setting offers an advantage over lenalidomide alone for patients who are newly diagnosed with multiple myeloma and anti-CD38 naïve."

In the AURIGA study, the D-R arm demonstrated a higher MRD-negative (10-5) conversion rate by 12 months compared to the R arm (50.5 percent vs 18.8 percent, odds ratio [OR] 4.51, P<0.0001) and a superior >6-month sustained MRD-negative rate (35.4 percent vs 13.9 percent, OR 3.40, P=0.0005). Complete response (CR) or better rates were also higher with D-R: 75.8 percent vs 61.4 percent (P=0.0255). The increased MRD-negative conversion rate resulted in a PFS favoring D-R (hazard ratio 0.53; 95% CI, 0.29-0.97) with an estimated 30-month rate of 82.7 percent compared to 66.4 percent for the R arm.1

"MRD-negativity is an important predictor of long-term progression-free survival for patients with multiple myeloma, and the FDA Oncologic Drugs Advisory Committee emphasized the value of this when it unanimously decided that MRD could be used as a primary endpoint in multiple myeloma clinical trials as a surrogate for PFS," said Imran Khan, Vice President, Medical Affairs, Hematology, Innovative Medicine, Johnson & Johnson. "These results, along with the data being presented from the Phase 3 CEPHEUS study, further underscore the promising potential of DARZALEX FASPRO for newly diagnosed patients, regardless of their transplant status."

Grade 3/4 treatment-related adverse events (TRAEs) occurred in 74 percent of patients treated with D-R and 67.3 percent of patients treated with R; infections (18.8 percent and 13.3 percent) and neutropenia (46.9 percent and 41.8 percent) were most common.1

Additional data from Phase 3 PERSEUS study demonstrate benefit of DARZALEX FASPRO-based induction, consolidation and maintenance regimens across cytogenetic risk populations

Expanded analyses of the Phase 3 PERSEUS study show that DARZALEX FASPRO in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) in induction/consolidation followed by a maintenance regimen of D-R induced deep and sustained MRD-negativity compared to VRd regardless of disease stage based on the second revised International Staging System (R2-ISS). In the revised high-risk subgroup, treatment with D-VRd followed by D-R maintenance results in higher rates of overall MRD-negativity at 10-6 with complete response or better compared to VRd (63.1 percent vs 32.4 percent; P<0.0001) with sustained MRD-negativity status for at least 12 months (42.3 percent vs 15.5 percent; P=0.0007).2

These data, including high-risk cytogenetic abnormalities (HRCAs), including gain(1q21) and amp(1q21), will be presented in an oral presentation at IMS (Abstract #OA – 48).

Phase 3 CASSIOPEIA MRD update shows deep and durable responses with DARZALEX in maintenance therapy

Updated MRD data from the Phase 3 CASSIOPEIA study demonstrate that including DARZALEX in both induction/consolidation and maintenance regimens resulted in deeper and more durable MRD-negative responses at 10-5 level vs bortezomib/thalidomide/dexamethasone (VTd) and observation: 77 percent vs 71 percent (P=0.0417). The benefit of DARZALEX monotherapy maintenance was demonstrated in both patients who received VTd induction and consolidation, as well as those who received DARZALEX and VTd. DARZALEX maintenance reduced the risk of progression or death by 24% in patients who received DARZALEX and VTd as induction and consolidation. These results will be presented in an oral presentation at IMS (Abstract #OA – 47).3

In the AURIGA, PERSEUS and CASSIOPEIA studies, the safety profiles were consistent with the known safety profiles for DARZALEX and DARZALEX FASPRO.

About the AURIGA Study
The randomized study (NCT03901963) included 200 patients aged 18-79 years with newly diagnosed multiple myeloma who are minimal residual disease (MRD)-positive after frontline autologous stem cell transplant. Patients received 1800 milligram (mg) daratumumab by subcutaneous (SC) injection in combination with lenalidomide (orally) as maintenance therapy for a maximum of 36 cycles. Each cycle is 28 days. Patients in the comparative arm will receive lenalidomide (orally) alone as maintenance therapy for a maximum of 36 cycles. Each cycle is 28 days.4

About the CEPHEUS Study
CEPHEUS (NCT03652064) is an ongoing, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd vs VRd in patients with newly diagnosed multiple myeloma who are transplant-ineligible or for whom transplant is not intended as initial therapy. Primary endpoint is MRD-negativity rate at 10-5 sensitivity threshold. Secondary endpoints include PFS, MRD-negative rate at 1 year, durable MRD negativity, ORR, time to and duration of response, PFS on next line of therapy, overall survival and safety. The trial has enrolled 396 patients in 13 countries.

About the PERSEUS Study
The PERSEUS study (NCT03710603) is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of DARZALEX FASPRO -VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for ASCT. Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm.5 The study is being conducted in 14 countries in Europe and Australia.

About the CASSIOPEIA Study
The randomized, open-label, multicenter, Phase 3 (NCT02541383) study is sponsored by the French Intergroupe Francophone du Myelome in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and Janssen Research & Development, LLC. This Phase 3 study included 1,085 newly diagnosed patients with previously untreated, symptomatic multiple myeloma who were eligible for high-dose chemotherapy and stem cell transplant. Part one of the study compared DARZALEX (D) in combination with bortezomib, thalidomide and dexamethasone (VTd) versus VTd induction and consolidation therapy in patients with NDMM who were eligible for autologous stem cell transplantation (ASCT) and demonstrated that D-VTd yielded deeper responses and improved PFS. Part two of the study compared D-maintenance therapy given every 8 weeks (at a reduced frequency treatment schedule compared to the standard long-term dosing frequency of every 4 weeks) versus observation. The primary endpoint in this part of the study is the proportion of patients who achieve a stringent complete response (sCR) 100 days after transplant. In the second part of the study, which is ongoing, patients who achieved a partial response or better in part one will undergo a second randomization to receive maintenance treatment with DARZALEX 16 mg/kg every eight weeks for up to two years or will be observed with no further treatment. The primary endpoint in this part of the study is PFS.6

About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.7 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.8 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.9 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.  People with multiple myeloma have a 5-year survival rate of 59.8 percent.10 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.11,12

About DARZALEX FASPRO and DARZALEX
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.14 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

DARZALEX (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.6

DARZALEX is the first CD38-directed antibody approved to treat multiple myeloma.6 DARZALEX-based regimens have been used in the treatment of more than 518,000 patients worldwide and more than 68,000 patients in the U.S. alone.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

Since 2020, the National Comprehensive Cancer Network (NCCN) has recommended daratumumab-based combination regimens for the treatment of newly diagnosed multiple myeloma and relapsed and refractory multiple myeloma.† For newly diagnosed multiple myeloma in non-transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide and dexamethasone as a Category 1 preferred regimen; daratumumab in combination with bortezomib, melphalan, and prednisone as another recommended Category 1 regimen; and daratumumab in combination with bortezomib, cyclophosphamide, and prednisone as another recommended Category 2A regimen. For newly diagnosed multiple myeloma in transplant candidates, the NCCN guidelines recommend daratumumab in combination with bortezomib, lenalidomide and dexamethasone as another recommended Category 2A regimen; daratumumab in combination with bortezomib, thalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; daratumumab in combination with carfilzomib, lenalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; and daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as a Category 2A regimen useful in certain circumstances. For maintenance in transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide as useful in certain circumstances. In relapsed/refractory myeloma, four daratumumab regimens are listed as Category 1 preferred regimens for early relapses (1-3 prior therapies): daratumumab in combination with lenalidomide and dexamethasone; daratumumab in combination with bortezomib and dexamethasone; daratumumab in combination with carfilzomib and dexamethasone; and daratumumab in combination with pomalidomide and dexamethasone [after one prior therapy including lenalidomide and a proteasome inhibitor (PI)]. The NCCN also recommends daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as another Category 2A regimen for early relapses (1-3 prior therapies) and as monotherapy as a Category 2A regimen useful in certain circumstances for early relapse patients after at least three prior therapies, including a PI and an immunomodulatory agent, or for patients who are double refractory to a PI and an immunomodulatory agent.

For more information, visit www.DARZALEX.com.

DARZALEX INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS
DARZALEX (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
CONTRAINDICATIONS
DARZALEX is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions
DARZALEX can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be lifethreatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision.

When DARZALEX dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX infusion. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX.

Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Neutropenia and Thrombocytopenia
DARZALEX may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX until recovery of neutrophils or for recovery of platelets.

Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX can cause fetal harm when administered to a pregnant woman. DARZALEX may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX and for 3 months after the last dose.

The combination of DARZALEX with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

ADVERSE REACTIONS

The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusionrelated reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.

Please click here to see the full Prescribing Information.

DARZALEX FASPRO INDICATIONS AND IMPORTANT SAFETY INFORMATION 

INDICATIONS
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

CONTRAINDICATIONS  
DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.  

WARNINGS AND PRECAUTIONS  

Hypersensitivity and Other Administration Reactions  
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO.

Systemic Reactions  
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Local Reactions  
In this pooled safety population, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.  

Neutropenia  
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.  

Thrombocytopenia  
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets.  

Embryo-Fetal Toxicity  
Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose.  

Interference With Serological Testing  
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.  

Interference With Determination of Complete Response  
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.  

ADVERSE REACTIONS  

In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.  

Please click here to see the full Prescribing Information for DARZALEX FASPRO.

Poseida Therapeutics Reports Positive Interim Phase 1 Results for Allogeneic CAR-T Therapy P-BCMA-ALLO1 with High Overall Response Rates in Heavily Pretreated Relapsed/Refractory Multiple Myeloma Patients

On September 27, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer and rare diseases, reported new interim clinical data from its ongoing Phase 1 trial of P-BCMA-ALLO1 in patients with relapsed/refractory multiple myeloma (RRMM) (Press release, Poseida Therapeutics, SEP 27, 2024, View Source [SID1234646898]). Data1 demonstrated a 91% overall response rate (ORR) and compelling safety results in the 23 heavily pretreated patients in Arm C, an optimized lymphodepletion arm. The new clinical data were presented today in an oral session at the 21st International Myeloma Society (IMS) Annual Meeting in Rio de Janeiro.

P-BCMA-ALLO1 is an investigational non-viral, stem cell memory T cell (TSCM)-rich allogeneic CAR-T cell therapy in Phase 1/1b clinical development for the treatment of patients with RRMM. The Company is developing this investigational off-the-shelf allogeneic CAR-T cell therapy with Roche as part of a broader collaboration focused on addressing blood cancers with Poseida’s TSCM-rich CAR-T platform.

"The compelling and differentiated results from the optimized lymphodepletion arms of the ongoing Phase 1 trial of P-BCMA-ALLO1 showed deep responses and a high response rate in patients with heavily pre-treated relapsed or refractory multiple myeloma, regardless of prior exposure to B-cell maturation antigen (BCMA)-targeting therapy. The high overall response rate of 91% is remarkable because most study participants in my center had rapidly proliferative refractory disease, in contrast with those treated in the pivotal clinical trials of FDA-approved autologous CAR-T therapies. Such patients treated in the current trial of P-BCMA ALLO1 would not have qualified for standard of care autologous CAR T therapy," said Bhagirathbhai R. Dholaria, M.D., Associate Professor of Medicine, Malignant Hematology & Stem Cell Transplantation at Vanderbilt University Medical Center in Nashville, Tenn., and trial investigator. "All patients in the Phase 1 trial have been treated quickly once enrolled, with no waiting for manufacturing, with no need for apheresis or bridging therapy, demonstrating key advantages of allogeneic CAR-T cell therapy."

"P-BCMA-ALLO1 is one of the most advanced allogeneic CAR-T in clinical development for multiple myeloma, manufactured using non-viral technology to produce a TSCM-rich therapy that has shown a compelling emerging product profile," said Kristin Yarema, Ph.D., president and chief executive officer of Poseida Therapeutics. "We are encouraged to see such a high overall response rate in an arm of the Phase 1 trial with optimized lymphodepletion, along with standout safety results across all arms, given that the study population was heavily pretreated, high-risk, and in general had many features that historically have led to a poor prognosis. We are excited to build on these data as we advance P-BCMA-ALLO1 in the Phase 1b part of the trial, which is currently enrolling patients."

New Interim Clinical Data from Phase 1 P-BCMA-ALLO1 Trial
The ongoing open-label, multicenter Phase 1/1b dose-escalation and expansion trial in patients with RRMM is assessing the safety and maximum tolerated dose of P-BCMA-ALLO1 (primary objective) and its anti-myeloma activity (secondary objective). As of September 6, 2024, 72 unique patients were enrolled as an intent-to-treat (ITT) population and were treated across four study arms (S, A, B and C) that included different P-BCMA-ALLO1 doses and lymphodepletion regimen combinations. Study participants were required to have received three or more prior lines of therapy, including a prior proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody. The trial enrolled a heavily pretreated patient population with 43% of patients having received prior BCMA-and/or GPRC5D targeting therapy. Most prior BCMA therapies included autologous CAR-T and/or T-cell engagers (TCE). Additionally, 33% of study participants were racial minorities, demonstrating Poseida’s commitment to underserved patient populations.

In the ITT population, 100% of patients enrolled as of the data cutoff were infused with P-BCMA-ALLO1. No patients required anti-myeloma bridging therapy or prophylaxis with steroids or tocilizumab, and there was no invasive apheresis or manufacturing wait time. The median time from enrollment to the start of study treatment was one day.

The ORR across all four study arms was 54%; 11% of patients achieved a complete response (CR) or a stringent complete response (sCR), and 33% achieved a very good partial response or higher (VGPR+). The median duration of response (DoR) was 232 days for study Arms A and B – the cohorts with six or more months of follow-up at the time of data cut-off. Expansion and persistence of the CAR-T cells in patients after infusion has been dependent upon the conditioning dose of cyclophosphamide. P-BCMA-ALLO1 levels measured in the peripheral blood and were much higher in patients in Arm C (cyclophosphamide 750 mg/m2/day) and Arm B (cyclophosphamide 1000 mg/m2/day) than in patients in Arm S (cyclophosphamide 300 mg/m2/day), and Arm A (cyclophosphamide 500 mg/m2/day). Arm C was identified as the optimized lymphodepletion arm based on cellular kinetics, safety and efficacy.

Data from Arm C of the Phase 1 P-BCMA-ALLO1 Trial
Results from 23 study participants in Arm C were highlighted in the oral session at IMS. Patients received cyclophosphamide 750 mg/m2/day and fludarabine 30 mg/m2/day and approximately 2×106 cells/kg P-BCMA-ALLO1. Some patients were treated in an outpatient setting. Arm C patient details include:

Nearly half (48%) were age 65 or older
All were heavily pretreated, with a median of six prior lines of anti-myeloma therapy and a maximum of 14
62% of patients had received prior BCMA-targeting therapy
29% had failed both a BCMA CAR-T and a bispecific TCE, and 29% had failed both a BCMA-targeting therapy and the GPRC5D-targeting TCE, talquetamab
Approximately two-thirds of patients (62%) had high-risk disease by cytogenetics and 38% had extramedullary disease
Efficacy results, which are still evolving, for the 23 patients in Arm C showed:

An ORR of 91%, with a 100% ORR in BCMA-naïve patients, an 86% ORR in those who had received at least one prior BCMA-targeting treatment (all had received prior CAR-T and/or TCE), and an 86% ORR in those who had received at least one prior BCMA-targeting treatment and/or talquetamab
22% achieved a CR or an sCR
48% achieved VGPR+
Median DoR could not be estimated at the time of data cut-off because the current median follow-up is less than 3.5 months (for pooled arms A and B, the median DoR was more than seven months (estimated range of five-10 months), with a median time to response of only 16 days)
P-BCMA-ALLO1 was well-tolerated with key safety results from Arm C, including:

No dose-limiting toxicities, Grade 3 or higher cytokine release syndrome (CRS) or immune effector cell neurotoxicity syndrome (ICANS). The incidence of Grade 1 or 2 CRS was 39% and the incidence of Grade 1 or 2 ICANS was 13%
The incidence of infections was 48%, including 30% that were Grade 1 or 2 and 17% that were Grade 3
Rapid cytopenia recovery in the vast majority of cases
No graft-vs-host disease (GvHD), hemophagocytic lymphohistiocytosis (HLH), Parkinsonism or cranial neuropathies observed
The safety results of P-BCMA-ALLO1 in arm C have been consistent with those observed in the other three arms of the Phase 1 trial, with a total safety database, including 72 unique patients
The ongoing P-BCMA-ALLO1 Phase 1/1b trial is enrolling patients using the Arm C lymphodepletion regimen described above, across two dosing cohorts, with dose optimization ongoing in Arm C.

Company-Hosted IMS Live Webcast and Conference Call Information
Poseida will host a live webcast and conference call tomorrow, Saturday, September 28, 2024, at 1 p.m. ET / 10 a.m. PT. The webcast will feature an expert panel of clinicians who will discuss the new clinical data and multiple myeloma treatment landscape. The panel will be moderated by Dr. Rizvi and include Dr. Dholaria and Thomas G. Martin, M.D., Clinical Professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program and Associate Director of the Myeloma Program at the University of California, San Francisco (UCSF), and Co-Leader of the Cancer Immunology & Immunotherapy Program at the UCSF Helen Diller Family Comprehensive Cancer Center.

The conference call can be accessed by dialing 800-225-9448 or 203-518-9708 (International) with the conference ID PSTX0928. The live webcast can be accessed using the link here, or by visiting the Events and Presentations section of the Poseida website at investors.poseida.com. After the live webcast, the event will remain archived on the Poseida website for approximately 90 days.

About P-BCMA-ALLO1
P-BCMA-ALLO1 is an allogeneic CAR-T product candidate licensed to Roche targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA, and interim clinical data presented at IMS in September 2024 support the Company’s belief that T stem cell (TSCM)-rich allogeneic CAR-Ts have the potential to offer effective, safe and reliable treatment addressing unmet needs in multiple myeloma. The U.S. Food and Drug Administration (FDA) has granted P-BCMA-ALLO1 Orphan Drug designation for multiple myeloma and Regenerative Medicine Advanced Therapy (RMAT) designation for adult patients with relapsed/refractory multiple myeloma after three or more prior lines of therapies including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.

P-BCMA-ALLO1 is currently being evaluated in a Phase 1/1b trial in patients with multiple myeloma. Additional information about the Phase 1/1b trial is available at www.clinicaltrials.gov using identifier: NCT04960579.

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Month: September 2024

Novel combination of TALVEY® (talquetamab-tgvs) and TECVAYLI® (teclistamab-cqyv) suggests high response rates and durable responses in triple-class refractory patients with relapsed or refractory multiple myeloma, including those with extramedullary disease

AbbVie Submits Biologics License Application to the FDA for Telisotuzumab Vedotin (Teliso-V) in Previously Treated Non-Small Cell Lung Cancer

DARZALEX FASPRO®-based quadruplet regimen significantly improves minimal residual disease negativity for newly diagnosed multiple myeloma patients for whom transplant is not planned

DARZALEX® (daratumumab)-based maintenance regimens show clinically meaningful deep and durable responses in transplant-eligible patients with newly diagnosed multiple myeloma

Poseida Therapeutics Reports Positive Interim Phase 1 Results for Allogeneic CAR-T Therapy P-BCMA-ALLO1 with High Overall Response Rates in Heavily Pretreated Relapsed/Refractory Multiple Myeloma Patients