New Interim Clinical Data from Phase 1 P-BCMA-ALLO1 Trial

On September 27, 2024 Poseida Therapeutics, Inc. (the "Company") 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 [SID1234646929]).

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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 F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. (collectively, "Roche") as part of a broader collaboration focused on addressing blood cancers with the Company’s TSCM-rich CAR-T platform.

Data, based on an efficacy cutoff date of September 6, 2024 and a safety cutoff date of July 31, 2024, 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 on September 27, 2024 in an oral session at the 21st International Myeloma Society Annual Meeting ("IMS") in Rio de Janeiro.

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 July 31, 2024, 72 unique patients were enrolled and had at least 4 weeks of follow-up 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 B-cell maturation antigen ("BCMA")- and/or G protein-coupled receptor class C group 5 member D ("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.

In the ITT population, 100% of patients enrolled 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, including patients 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.

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.

Roche Collaboration

Under that certain Collaboration and License Agreement, dated July 30, 2022, as amended (the "Roche Agreement"), by and between the Company and Roche, Roche did not timely exercise its option to acquire an exclusive license to the Company’s BCMA/CD19 Allo CAR T-cell therapy program for the development of hematological malignancies (the "BCMA/CD19 Program"), and, as a result, the rights held by Roche with respect to the BCMA/CD19 Program under the Roche Agreement have been deemed terminated. The Company plans to continue development of the BCMA/CD19 Program internally.

IASO Bio Presented the Outcomes of Relapsed/Refractory Multiple Myeloma (R/RMM) Patients with Renal Impairment Treated with Equecabtagene Autoleucel (Fucaso™) at 2024 IMS Annual Meeting

On September 27, 2024 IASO Biotherapeutics ("IASO Bio"), a biopharmaceutical company dedicated to discovering, developing, manufacturing and commercializing innovative cell therapy and antibody products, reported a poster presentation of the outcomes of relapsed/refractory multiple myeloma (R/RMM) patients with renal impairment (RI) treated with the fully human anti-BCMA CAR-T cell therapy Equecabtagene Autoleucel (Eque-cel, FucasoTM), from the pivotal phase 2 FUMANBA-1 study at the 2024 International Myeloma Society (IMS) Annual Meeting (Press release, IASO Biotherapeutics, SEP 27, 2024, View Source [SID1234646906]). Results indicate that Eque-cel achieve equivalent efficacy and safety for R/RMM patients with renal impairment and improve the renal function as well.

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Abstract Number: P-100
Abstract Title: The Outcomes of R/R MM Patients with Renal Impairment (RI) Treated with Eque-cel in the Pivotal Phase 2 FUMANBA-1 Study
Presentation Date: September 26, 2024(UTC-3)

A total of 91 subjects, all without prior CAR-T treatment, were enrolled in the FUMANBA-1 study to receive Eque-cel, with a median follow-up of 18.07 months. Subjects were divided into RI group and non-RI group, based on creatinine clearance (CrCl) levels at the time of CAR-T therapy, of which 28 subjects had RI with CrCl between 40 and 70 ml/min, and 63 belonged to non-RI group, with CrCl>70 ml/min.

The baseline characteristics in the RI group were comparable to those in the non-RI group. The RI group achieved a response as rapid and deep as the non-RI group. Long-term efficacy in the RI group were not inferior (as shown in Figure1) as non-PI group. In terms of safety, both group developed cytokine release syndrome (CRS) Only one case of grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in the non-RI group, while no cases of ICANS occurred in the RI group. A slightly higher prevalence of short-term severe cytopenia was noted in the RI group, but recovered by day 60.

Conclusions: In the FUMANBA-1 study, R/RMM patients with RI could achieved a similarly rapid, deep, and durable response with Eque-cel treatment without compromising safety status. Additionally, renal function was improveddue to the clearance of myeloma cells by Eque-cel.

The principal investigator of this study, Professor Lugui Qiu, from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and Professor Chunrui Li, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, stated: "In the past, we were concerned about the potential intolerance of R/R MM patients with impaired renal function to CAR-T treatment. The current study confirmed that even in patients with renal impairment, Eque-cel can induce rapid, deep, and durable remission, with efficacy comparable to that of patients without renal impairment. This data provides invaluable insights for clinical treatment with Eque-cel for camplcated case.

Dr. Yongke Zhang, Chief Scientific Officer of IASO Bio, said: "We are pleased to present the retrospective study on the use of Eque-cel (FucasoTM) for treating R/RMM patients with renal impairment at the IMS Annual Meeting. Data from the FUMANBA-1 study demonstrated the promising efficacy and safety of Eque-cel in this patient population, with the added benefit of improving renal function. We believe CAR-T therapy will offer new therapeutic options for R/RMM patients with moderate to severe renal function impairment, enabling broader application in the field of myeloma treatment."

About FUMANBA-1 Study

The FUMANBA-1 Study is a Phase Ib/II, single-arm, multicenter study to assess the efficacy and safety of the investigational drug Equecabtagene Autoleucel, a fully human BCMA CAR-T cell therapy, in patients with R/R MM who have received 3 or more lines of treatment.

Anbogen Announces Drug Supply Collaboration with BeiGene to Evaluate Combination Therapy in Colorectal Cancer

On September 27, 2024 Anbogen, a clinical-stage biotech company, reported a drug supply collaboration to evaluate the combination of Anbogen’s HDAC inhibitor, ABT-301, with BeiGene’s anti-PD-1 antibody tislelizumab, in patients with mismatch repair–proficient (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC) in a global Phase II trial (Press release, Anbogen Therapeutics, SEP 27, 2024, View Source [SID1234646905]). Under the terms of the agreement, BeiGene will supply tislelizumab to Anbogen for the study.

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In 2020, over 1.9 million new cases of colorectal cancer were diagnosed globally. Immune checkpoint inhibitors (ICIs) have emerged as a primary treatment for metastatic colorectal cancer (mCRC) with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). However, this innovative therapy benefits only a small fraction of patients, as less than 5% of mCRC cases exhibit dMMR/MSI-H. Consequently, there remains a significant unmet need for the 95% of patients with pMMR/MSS tumors, who do not respond to ICIs.

ABT-301, a novel HDAC inhibitor, has shown promising safety and pharmacokinetic profiles in a prior Phase 1 study as a single agent. Preclinical studies indicate that ABT-301 enhances the effectiveness of anti-PD-1/anti-PD-L1 therapies by increasing CD8+ cytotoxic T cells and decreasing monocytic myeloid-derived suppressor cells within both the tumor and circulation, and inhibiting angiogenesis. These immune response enhancements may broaden the efficacy of ICIs in colorectal cancer patients. The upcoming Phase II study will investigate the effectiveness of treatment regimens combining ABT-301 and tislelizumab, with and without Bevacizumab, in pMMR/MSS mCRC patients with significant unmet needs.

"We are excited to partner with BeiGene to investigate this promising combination therapy," said John Hsu, CEO of Anbogen. "ABT-301 has shown potential in preclinical studies, and we believe that combining it with tislelizumab could provide a new therapeutic option for patients with colorectal cancer."

The clinical trial will be conducted in multiple centers and will evaluate the safety, tolerability, and preliminary efficacy of the combination therapy in patients with advanced MSS CRC. The study is expected to begin enrollment in the first quarter of 2025.

TALVEY® (talquetamab-tgvs) and DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) based combination shows deep and durable responses in patients with relapsed or refractory multiple myeloma

On September 27, 2024 Johnson & Johnson (NYSE: JNJ) reported updated results from the investigational Phase 1b TRIMM-2 study evaluating the combination of TALVEY (talquetamab-tgvs) with DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) and pomalidomide in patients with relapsed or refractory multiple myeloma that demonstrated an overall response rate (ORR) of 82 percent, further supporting the investigation of this combination (Press release, Johnson & Johnson, SEP 27, 2024, View Source [SID1234646904]). These data were featured in an oral presentation at the 2024 International Myeloma Society Annual Meeting (Abstract #OA – 01).

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The results from the Phase 1b TRIMM-2 study evaluating TALVEY, the first bispecific T-cell engager to target GPRC5D, combined with DARZALEX FASPRO, the first subcutaneous anti-CD38 monoclonal antibody, and pomalidomide included patients who received at least three prior lines of therapy, including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), or were double refractory to a PI and IMiD and had not received anti-CD38 therapy in the previous 90 days.1

At data cutoff, 77 patients had received TALVEY in doses of 0.4 mg/kg weekly (QW) or 0.8 mg/kg biweekly (Q2W), with step-up doses, combined with DARZALEX FASPRO and pomalidomide. In the QW arm (n=18), the overall response rate (ORR) was 100 percent, with 56 percent having a complete response (CR) or better. The Q2W arm (n=59) achieved 76 percent ORR, with 56 percent achieving CR or better. The median duration of response (DOR) in the Q2W arm was 26.4 months, and the median progression-free survival (PFS) was 20.3 months. Results showed 52 percent of patients who are anti-CD38 refractory (n=64) achieved CR or better and 70.8 percent of patients who received prior chimeric antigen receptor T cell (CAR-T) therapy (n=24) achieved CR or better. Patients who had received prior bispecific antibodies (n=29) achieved an 82.8 percent ORR.1

"The deep and durable responses shown in these latest results from TRIMM-2 further support the potential of TALVEY in combination with DARZALEX FASPRO, which has become a standard of care in multiple myeloma, and pomalidomide," said Nizar Bahlis, M.D., Associate Professor, Arnie Charbonneau Cancer Institute, University of Calgary and presenting author.* "With high overall response rates seen across cohorts, this combination shows potential for significant disease control and survival in patients who have received multiple lines of prior therapy, including exposure to prior bispecific antibodies."

The safety profile of this combination reflected the known profiles of TALVEY, DARZALEX FASPRO and pomalidomide. Despite the incidence of neutropenia (83.3 percent in the QW arm and 79.7 percent in the Q2W arm) being high, the Grade 3/4 infection rate was generally low (16.7 percent and 37.3 percent, respectively). The majority of on-target, off-tumor treatment-related adverse events (TRAEs), including oral (100 percent in the QW arm, 84.7 percent in Q2W arm), skin (88.9 percent, 67.8 percent), nail (83.3 percent, 55.9 percent) and weight decrease (66.7 percent, 49.2 percent) were low-grade (Grade 1/2) and did not lead to discontinuation of therapy. These results support further investigation of TALVEY in combination with DARZALEX FASPRO, with or without pomalidomide, in patients who have received earlier lines of therapy, including a proteasome inhibitor and lenalidomide, which is currently being investigated in the registrational, Phase 3 MonumenTAL-3 study.1

"We continue to be encouraged by the potential versatility of TALVEY as a combination partner with other therapies to address unmet needs for patients with relapsed or refractory multiple myeloma who have limited treatment options at this advanced stage," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Innovative Medicine at Johnson & Johnson. "By simultaneously targeting GPRC5D and CD38 on myeloma cells with the combination of TALVEY and DARZALEX FASPRO, we are aiming to attack multiple myeloma in different ways to help improve outcomes for patients with this serious illness and limited treatment options."

Additional data underscoring the combinability of TALVEY from the RedirecTT-1 study will also be presented at IMS. Results from the TRIMM-2 study were previously presented at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting.

About TRIMM-2 Study
The TRIMM-2 (NCT04108195) study is an ongoing Phase 2 study of DARZALEX FASPRO regimens in combination with TALVEY for the treatment of patients with multiple myeloma. The primary objectives of the TRIMM-2 study were to identify the Phase 2 dose (RP2D) for each component of the treatment combination (Part One); characterize the safety of the treatment combination at the RP2D (Part 2); and assess antitumor activity, pharmacokinetics and pharmacodynamics for the combination treatment (Part 3). Patients in the study (N=65) all had multiple myeloma and had received a minimum three prior lines of therapy or were double refractory to a proteasome inhibitor (PI) and an immunomodulatory agent; patients who had been exposed or refractory to an anti-CD38 therapy more than ninety days prior to the start of the trial were also included, as well as those refractory to anti-CD38 therapy.

About MonumenTAL-3
The MonumenTAL-3 (NCT05455320) study is an ongoing Phase 3 study of TALVEY in combination with DARZALEX FASPRO with or without pomalidomide compared to DARZALEX FASPRO combined with pomalidomide and dexamethasone in patients with relapsed of refractory multiple myeloma who have received at least one prior line of therapy.

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.9 Since FDA approval, 1,500 patients were treated with TALVEY. The European Commission (EC) granted conditional marketing authorization (CMA) of TALVEY 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.10

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 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.11 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

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.

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.

BioProtect Balloon Spacer Study Published in International Journal of Radiation Oncology, Biology, Physics and Featured at ASTRO 2024, Demonstrates Significant Rectal Protection

On September 27, 2024 BioProtect Ltd, a private MedTech company focused on providing innovative, biodegradable spacing solutions, reported the publication of its pivotal study’s successful outcomes in the International Journal of Radiation Oncology, demonstrating a high level of efficacy and safety for its biodegradable balloon spacer (Press release, BioProtect, SEP 27, 2024, View Source [SID1234646903]).

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"The randomized, 220-patient, multi-center, prospective, clinical study demonstrated a significant dose reduction to the rectum in 97.9% of the patients, while maintaining very low rates of rectal toxicity compared to the control arm, meeting both study’s primary endpoints," said Daniel Song, MD, Professor of Radiation Oncology, Johns Hopkins University, who is the study’s principal investigator. Dr. Song will present the pivotal study data alongside other leading experts at the upcoming American Society for Radiation Oncology (ASTRO) Annual Meeting in Washington, D.C. in late September.

"This recent data further solidifies our confidence in supporting the U.S. commercialization of the BioProtect Balloon spacer, which received FDA clearance in August 2023 for enhancing rectal protection during radiation therapy for prostate cancer patients," said BioProtect’s CEO, Itay Barnea. "Following its FDA clearance, the device has been successfully implanted in over 2,000 U.S. patients since launch. Our close, ongoing collaboration with the clinical community ensures that more patients and physicians can benefit from its superior characteristics as we continue to expand its adoption in cancer treatment centers nationwide."