Puma Biotechnology Presents Final Results from the Biliary Tract Cohort of the Phase 2 SUMMIT ‘Basket’ Trial of Neratinib at the ASCO 2022 Annual Meeting

On June 4, 2022 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that final results from the Phase II SUMMIT ‘basket’ trial, assessing the efficacy of neratinib in treatment-refractory patients with metastatic biliary tract cancers with somatic HER2 mutations at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Puma Biotechnology, JUN 4, 2022, View Source [SID1234615575]). The presentation entitled "Targeting HER2 mutation-positive advanced biliary tract cancers with neratinib: Final results from the phase 2 SUMMIT ‘basket’ trial" was presented at the Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary Poster Session (#4079) by James J. Harding, MD, Regional Director, Early Drug Development, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, an investigator of the trial. A copy of this poster presentation is available on the Puma website.

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Neratinib is an irreversible, pan-HER, oral tyrosine kinase inhibitor. The Phase II SUMMIT trial is an open-label, single-arm, multi-cohort, ‘basket’ trial of neratinib in patients with solid tumors that harbor oncogenic somatic HER2 mutations. The study included a cohort of treatment-refractory patients with metastatic biliary tract cancers (BTCs). While HER2 overexpression is associated with an increased risk of disease recurrence in patients with resected BTC, there is limited data on targeting HER2 mutations in these patients.

Efficacy results from the BTC cohort of 25 patients (11 cholangiocarcinoma, 10 gallbladder, 4 ampullary cancers) demonstrated an overall response rate (ORR) of 16%, 95% CI 4.5-36.1%), median progression free survival (PFS) of 2.8 months and overall survival (OS) of 5.4 months. The most common HER2 mutation was S310F. Co-occurring oncogenic alterations in TP53 and CDKN2A appeared to associate with worse outcome. The most frequently observed toxicity was diarrhea (56% any grade).

"Patients with biliary tract cancers have poor survival and a paradigm of treatment is precision medicine," said Dr. James J. Harding, MD Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College and an investigator of the trial. "In addition, HER2-mutant biliary cancers are uncommon and understudied. Results of the SUMMIT BTC cohort demonstrated that neratinib offers some respite for these underserved patients. However, additional studies are needed to determine if combining neratinib with other cancer therapies could significantly extend survival in patients and thereby improve their quality of life."

Alan H. Auerbach, Chief Executive Officer and President of Puma, added, "Previous findings indicate that neratinib has a promising role as a treatment option for rare cancers. With the results from this cohort and others in the SUMMIT trial, we can continue to identify new groups of patients who can benefit from neratinib."

Longer-Term Data from CARTITUDE Program Continue to Show Deep and Durable Responses with Ciltacabtagene Autoleucel Across Lines of Therapy in Patients with Multiple Myeloma

On June 4, 2022 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, presented today new and updated results from the CARTITUDE clinical development program studying ciltacabtagene autoleucel (cilta-cel) in the treatment of multiple myeloma at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Legend Biotech, JUN 4, 2022, View Source [SID1234615574]). Earlier data from the CARTITUDE-1 study supported recent regulatory approvals for CARVYKTI by the U.S. Food and Drug Administration and the European Commission, and ongoing results from the multi-cohort CARTITUDE-2 study are being used to inform future trials of CARVYKTI treatment in multiple patient populations and treatment settings.

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Longer-Term CARTITUDE-1 Data Continue to Show Deep and Durable Responses

Data from the ongoing Phase 1b/2 CARTITUDE-1 study continue to show deep and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma at a median 28-month follow up (MFU), with an overall response rate (ORR) of 98 percent (95 percent Confident Interval [CI], 92.7-99.7).1,2

Responses in 97 patients treated with CARVYKTI were sustained from the 22-month median follow-up data previously presented at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, with 83 percent of patients achieving a stringent complete response (sCR) at median 28 MFU.1 Median progression-free survival (PFS) and median overall survival (OS) were not reached at time of follow-up, suggesting long-term durability of responses and survival for patients.1 Two-year PFS and OS rates were 55 percent (95 percent CI, 44.0–64.6) and 70 percent (95 percent CI, 60.1–78.6), respectively.1 Sixty-one patients had samples evaluable for minimal residual disease (MRD) status, and of those, 92 percent achieved MRD negativity at the 10-5 threshold.1 Of those evaluable, MRD negativity was sustained for more than 6 months in 68 percent and more than 12 months in 55 percent of patients.1 Two-year PFS rates in patients who achieved sustained MRD negativity for 6 months or longer and 12 months or longer were 73 percent (95 percent CI, 52.1 to 85.9) and 79 percent (95 percent CI, 51.5 to 91.8), respectively. In these same patients, two-year OS rates were 94 percent (95 percent CI, 76.1 to 98.3) and 91 percent (95 percent CI, 67.7 to 97.6), respectively.1

The CARTITUDE-1 study included patients who received a median of six prior treatment regimens (range, 3-18).1 All patients were triple-class [immunomodulatory agent (IMiD), proteasome inhibitor (PI) and anti-CD38 antibody] exposed, while 42 percent of patients were penta-drug refractory and 99 percent of patients were refractory to the last line of therapy.1

"After more than two years of follow-up, cilta-cel continues to provide durable responses for patients with relapsed or refractory multiple myeloma who often have exhausted multiple lines of therapy and face poor prognoses," said Saad Z. Usmani, M.D., M.B.A., F.A.C.P., Chief of Myeloma Service, at Memorial Sloan Kettering Cancer Center, and study investigator. "This population of patients has an unmet need, and it is exciting that we have a treatment option that can keep disease progression at bay."

Median time to first response was one month (range, 0.9-10.7 months), with responses deepening over time.1 Additionally, median time to best response was 2.6 months (range, 0.9-17.8 months) and median time to complete response (CR) or better was 2.9 months (range, 0.9-17.8 months).1

At 28-month median follow up, the most common hematologic adverse events (AEs) observed were neutropenia (96 percent); anemia (81 percent); thrombocytopenia (79 percent); leukopenia (62 percent); and lymphopenia (54 percent). Since the primary 12-month publication,3 no new events of CRS (no changes in incidence, time to onset, or duration) occurred and one new case of Parkinsonism (also referred to as movement and neurocognitive treatment-emergent adverse events) occurred.1

CARTITUDE-2 Data Reinforce Potential for Use in Earlier-Line of Treatment

Results from the multicohort Phase 2 CARTITUDE-2 study (NCT04133636) evaluating cilta-cel safety and efficacy in various clinical settings for patients with multiple myeloma were also presented at ASCO (Free ASCO Whitepaper) 2022, demonstrating the promise of CARVYKTI earlier in the course of multiple myeloma treatment.

Updated data from Cohort A examined the safety and efficacy of cilta-cel in 20 patients with multiple myeloma after one to three prior lines of therapy and who are lenalidomide-refractory (Abstract #8020).4 At a median follow-up of 17.1 months, the ORR was 95 percent, which included 90 percent of patients achieving CR or better and 95 percent achieving very good partial response (VGPR) or better. The median time to first response was one month and the median time to best response was 2.6 months. The 15-month PFS rate was 70 percent.4 Of the 16 patients who were MRD-evaluable, all achieved MRD negativity at 10-5.4

Results from Cohort B of the study, evaluating the safety and efficacy of cilta-cel in patients relapsed or refractory multiple myeloma who received one prior line of therapy including a PI and IMiD and had disease progression within 12 months of treatment with autologous stem cell transplant (ASCT) or within 12 months of the start of antimyeloma therapy for patients who have not had ASCT, were also presented (Abstract #8029).5 At a median of 13 months follow-up, 19 patients treated in this cohort achieved an ORR of 100 percent, with 90 percent of patients achieving a CR or better, and 95 percent of patients achieving a VGPR or better.5 Median time to first response was one month (range, 0.9-9.7) and median time to best response was 5.1 months.5 The 12-month PFS rate was 90 percent. Of the 15 patients who were MRD-evaluable, 14 achieved MRD negativity at 10-5.5

In both of these cohorts from CARTITUDE-2, the overall safety profile, including incidence of CRS and most common hematologic AEs, was consistent with that of CARTITUDE-1.5

"On the heels of the approval of CARVYKTI in heavily pre-treated patients, we’re pleased to see the longer-term depth and durability of responses in the CARTITUDE-1 study," said Ying Huang, Chief Executive Officer of Legend Biotech. "In addition, the follow up results from the ongoing CARTITUDE-2 Cohort A and B studies support the potential of cilta-cel as a therapeutic option for earlier lines of treatment. We are inspired by the promise of cilta-cel in new patient populations and look forward to helping multiple myeloma patients who continue to have unmet needs across the treatment paradigm."

Disclosure: Dr. Usmani has provided consulting, advisory, and speaking services to Legend Biotech and Janssen, Biotech, Inc.

About CARVYKTI (Ciltacabtagene autoleucel; cilta-cel)

CARVYKTI is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells. The CARVYKTI CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.6

In December 2017, Legend Biotech Corporation entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel.

In February 2022, CARVYKTI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with relapsed or refractory multiple myeloma.7 In May 2022, the European Commission (EC) granted conditional marketing authorization of CARVYKTI for the treatment of adults with relapsed and refractory multiple myeloma.8 Cilta-cel was granted Breakthrough Therapy Designation in the U.S. in December 2019 and in China in August 2020. In addition, cilta-cel received a PRIority MEdicines (PRIME) designation from the European Commission in April 2019. Cilta-cel also received Orphan Drug Designation from the U.S. FDA in February 2019, from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020. In May 2022, the European Medicines Agency’s Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained on the basis of clinical data demonstrating improved and sustained complete response rates following treatment.9

About CARTITUDE-1

CARTITUDE-1 (NCT03548207)10 is an ongoing Phase 1b/2, open-label, single arm, multi-center trial evaluating cilta-cel for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received at least three prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody. Of the 97 patients enrolled in the trial, 99 percent were refractory to the last line of treatment and 88 percent were triple-class refractory, meaning their cancer did not respond, or no longer responds, to an IMiD, a PI and an anti-CD38 monoclonal antibody.

About CARTITUDE-2

CARTITUDE-2 (NCT04133636)11 is an ongoing Phase 2 multicohort study evaluating the safety and efficacy of cilta-cel in various clinical settings. Cohort A included patients who had progressive multiple myeloma after 1–3 prior lines of therapy, including PI and IMiD, were lenalidomide refractory, and had no prior exposure to BCMA-targeting agents. Cohort B included patients with early relapse after initial therapy that included a PI and IMiD. The primary objective was to evaluate the percentage of patients with negative minimal residual disease (MRD).

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.12 In 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.13 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.14 Although treatment may result in remission, unfortunately, patients will most likely relapse.15 Patients who relapse after treatment with standard therapies, including protease inhibitors, immunomodulatory agents, and an anti-CD38 monoclonal antibody, have poor prognoses and few treatment options available.16,17

CARVYKTI Important Safety Information

INDICATIONS AND USAGE

CARVYKTI (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, and PROLONGED and RECURRENT CYTOPENIA

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI. Do not administer CARVYKTI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI. Provide supportive care and/or corticosteroids as needed.
Parkinsonism and Guillain-Barré syndrome and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI.
CARVYKTI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI REMS Program.
WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome (CRS) including fatal or life-threatening reactions, occurred following treatment with CARVYKTI in 95% (92/97) of patients receiving ciltacabtagene autoleucel. Grade 3 or higher CRS (2019 ASTCT grade)1 occurred in 5% (5/97) of patients, with Grade 5 CRS reported in 1 patient. The median time to onset of CRS was 7 days (range: 1-12 days). The most common manifestations of CRS included pyrexia (100%), hypotension (43%), increased aspartate aminotransferase (AST) (22%), chills (15%), increased alanine aminotransferase (14%) and sinus tachycardia (11%). Grade 3 or higher events associated with CRS included increased AST and ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, respiratory failure, acute kidney injury, disseminated intravascular coagulation, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased C-reactive protein, ferritin, blood alkaline phosphatase and gamma-glutamyl transferase.

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Sixty-nine of 97 (71%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of ciltacabtagene autoleucel. Forty-four (45%) patients received only tocilizumab, of whom 33 (34%) received a single dose and 11 (11%) received more than one dose; 24 patients (25%) received tocilizumab and a corticosteroid, and one patient (1%) received only corticosteroids. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI.

Monitor patients at least daily for 10 days following CARVYKTI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. Neurologic toxicities, which may be severe, life-threatening or fatal, occurred following treatment with CARVYKTI.

Neurologic toxicities, which may be severe, life-threatening or fatal, occurred following treatment with CARVYKTI. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, Guillain-Barré Syndrome, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time.

Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel in 26% (25/97) of patients, of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic toxicities were also observed in two ongoing studies.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Patients receiving CARVYKTI may experience fatal of life-threatening ICANS following treatment with CARVYKTI, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS.

ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97). The median time to onset of ICANS was 8 days (range 1-28 days). All 22 patients with ICANS had CRS. The most frequent (≥5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%) and headache (6%). Monitor patients at least daily for 10 days following CARVYKTI infusion at the REMS-certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms.

Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

Parkinsonism: Of the 25 patients in the CARTITUDE-1 study experiencing any neurotoxicity, five male patients had neurologic toxicity with several signs and symptoms of parkinsonism, distinct from immune effector cell-associated neurotoxicity syndrome (ICANS). Neurologic toxicity with parkinsonism has been reported in other ongoing trials of ciltacabtagene autoleucel. Patients had parkinsonian and nonparkinsonian symptoms that included tremor, bradykinesia, involuntary movements, stereotypy, loss of spontaneous movements, masked facies, apathy, flat affect, fatigue, rigidity, psychomotor retardation, micrographia, dysgraphia, apraxia, lethargy, confusion, somnolence, loss of consciousness, delayed reflexes, hyperreflexia, memory loss, difficulty swallowing, bowel incontinence, falls, stooped posture, shuffling gait, muscle weakness and wasting, motor dysfunction, motor and sensory loss, akinetic mutism, and frontal lobe release signs. The median onset of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range 15-108) from infusion of ciltacabtagene autoleucel.

Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson’s disease, for the improvement or resolution of parkinsonism symptoms following CARVYKTI treatment.

Guillain-Barré Syndrome: A fatal outcome following Guillain-Barré Syndrome (GBS) has occurred in another ongoing study of ciltacabtagene autoleucel despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with MillerFisher variant of GBS, encephalopathy, motor weakness, speech disturbances and polyradiculoneuritis.

Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS.

Peripheral Neuropathy: Six patients in CARTITUDE-1 developed peripheral neuropathy. These neuropathies presented as sensory, motor or sensorimotor neuropathies. Median time of onset of symptoms was 62 days (range 4-136 days), median duration of peripheral neuropathies was 256 days (range 2-465 days) including those with ongoing neuropathy. Patients who experienced peripheral neuropathy also experienced cranial nerve palsies or GBS in other ongoing trials of ciltacabtagene autoleucel.

Cranial Nerve Palsies: Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE-1. All three patients had 7th cranial nerve palsy; one patient had 5th cranial nerve palsy as well. Median time to onset was 26 days (range 21-101 days) following infusion of ciltacabtagene autoleucel. Occurrence of 3rd and 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy after improvement, and occurrence of peripheral neuropathy in patients with cranial nerve palsy have also been reported in ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS: Fatal HLH occurred in one patient (1%), 99 days after ciltacabtagene autoleucel. The HLH event was preceded by prolonged CRS lasting 97 days. The manifestations of HLH/MAS include hypotension, hypoxia with diffuse alveolar damage, coagulopathy, cytopenia, and multi-organ dysfunction, including renal dysfunction. HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards.

CARVYKTI REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI REMS.

Further information is available at www.CARVYKTIrems.com or 1-844-672-0067.

Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI infusion. One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia.

In CARTITUDE-1, 30% (29/97) of patients experienced prolonged Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Day 30 following ciltacabtagene autoleucel infusion.

Recurrent Grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia and anemia were seen in 63% (61/97), 18% (17/97), 60% (58/97), and 37% (36/97) after recovery from initial Grade 3 or 4 cytopenia following infusion. After Day 60 following ciltacabtagene autoleucel infusion, 31%, 12% and 6% of patients had a recurrence of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Eighty-seven percent (84/97) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Six and 11 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death.

Monitor blood counts prior to and after CARVYKTI infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines.

Infections: CARVYKTI should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening or fatal infections occurred in patients after CARVYKTI infusion.

Infections (all grades) occurred in 57 (59%) patients. Grade 3 or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4 infections with an unspecified pathogen occurred in 17%, viral infections in 7%, bacterial infections in 1%, and fungal infections in 1% of patients. Overall, four patients had Grade 5 infections: lung abscess (n=1), sepsis (n=2) and pneumonia (n=1).

Monitor patients for signs and symptoms of infection before and after CARVYKTI infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 10% of patients after ciltacabtagene autoleucel infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated.

Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV), or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.

Hypogammaglobulinemia was reported as an adverse event in 12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 92% (89/97) of patients. Monitor immunoglobulin levels after treatment with CARVYKTI and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI treatment, and until immune recovery following treatment with CARVYKTI.

Hypersensitivity Reactions have occurred in 5% (5/97) of patients following ciltacabtagene autoleucel infusion. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage appropriately according to the severity of the hypersensitivity reaction.

Secondary Malignancies: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc., at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancy of T cell origin.

Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities.

ADVERSE REACTIONS

The most common non-laboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections of unspecified pathogen, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common laboratory adverse reactions (incidence greater than or equal to 50%) include thrombocytopenia, neutropenia, anemia, aminotransferase elevation, and hypoalbuminemia. Please read full

Please read full Prescribing Information including Boxed Warning for CARVYKTI.

Atara Biotherapeutics Announces First Clinical Data from Ongoing Tab-cel® European Multicenter Expanded Access Program (EAP) at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and Update on Tab-cel EMA Regulatory Progress

On June 4, 2022 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported EMA regulatory progress and tabelecleucel (tab-cel) clinical outcomes (Press release, Atara Biotherapeutics, JUN 4, 2022, View Source [SID1234615573]). Data is reported from the multicenter Expanded Access Program (EAP) study in Europe for patients with relapsed or refractory (r/r) Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD) following solid organ transplant (SOT) or hematopoietic cell transplant (HCT) and will be featured in a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 3-7, 2022, in Chicago, IL.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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In the ongoing EAP, 22 patients from the first European centers consented to this observational study, of which 16 patients presented with EBV+ PTLD and six with EBV+ non-PTLD between July 2020 and November 2021. The primary objective of the study is to describe the demographics and disease characteristics of patients with EBV+ diseases treated with tab-cel under the EAP. Secondary objectives are to describe the tab-cel dosing pattern, to evaluate clinically relevant treatment outcomes, and to describe the safety of tab-cel in patients with EBV+ diseases treated under the EAP.

Of the 16 EBV+ PTLD patients, 15 received at least one dose of tab-cel. Overall, nine out of 15 (60%) tab-cel treated patients achieved a response as assessed by the treating physician, with six complete responses (CRs) and three partial responses (PRs). Of the nine responses, eight were observed after the first treatment cycle of tab-cel.

Safety findings were consistent with previously published data. All treatment-emergent events were assessed as unrelated to tab-cel by the treating physician and were consistent with patients’ underlying diseases. Further detail on baseline demographics and disease characteristics, and additional safety data including tab-cel exposure details, will be presented at the conference.

"We are pleased to share the latest data from our EAP in Europe demonstrating clinically meaningful outcomes for patients with EBV+ PTLD, a rare and aggressive disease with no approved treatment options, in line with the favorable safety and efficacy profile from previously reported studies including the pivotal Phase 3 ALLELE study," said Jakob Dupont, M.D., Head of Global Research & Development at Atara. "In addition, we now welcome the completion of our pre-approval inspections as a key milestone on our road to achieving approval in the EU."

Separately, Atara announced completion of all six pre-approval inspections required to support the Marketing Authorization Application for tab-cel in Europe, with the Good Manufacturing Practice (GMP) compliance certificates required to support the filing expected by July. Combined with the recent Day 120 critical assessment report, where the European Medicines Agency (EMA) considered the comparability data between clinical and commercial manufacturing versions as sufficient to demonstrate comparability, Atara continues to expect European Commission approval in Q4 2022.

ASCO presentation details:

Title: Demographics and treatment outcomes in patients with EBV+ PTLD treated with off-the-shelf EBV-specific CTL (tabelecleucel) under an ongoing expanded access program in Europe: First analyses.
Presenting Author: Ralf Trappe, M.D., DIAKO Evangelisches Diakonie-Krankenhaus Bremen, Bremen, Germany
Date & Time: Saturday, June 4, 2022, at 8-11 a.m. CDT/6-9 a.m. PDT
Abstract Number: 7530
Poster Number: 184
Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Location: McCormick Place Convention Center Chicago, Hall A

Circulating Tumor DNA Guides Chemotherapy Use in Stage II Colon Cancer

On June 4, 2022 TGen reported that PHOENIX Tumor DNA circulating in the bloodstream can help clinicians decide whether chemotherapy is right for their patients who have undergone surgery for stage II colon cancer, according to a breakthrough study published online in The New England Journal of Medicine and presented today at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract LBA100) (Press release, TGen, JUN 4, 2022, View Source [SID1234615572]). An international team that included investigators from the Translational Genomics Research Institute (TGen), part of City of Hope, conducted the study to lend clarity to the role of adjuvant chemotherapy in this setting.

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Previous studies suggested that the presence of circulating tumor DNA (ctDNA), the small fragments of a cancer’s genetic material shed into the blood, predicted a recurrence of the cancer after surgery, while the absence of ctDNA predicted a low recurrence risk. The real-world study is thought to be the first to use ctDNA to guide follow-up chemotherapy decisions in stage II colon cancer patients after surgery to determine if certain patients can be spared from this form of treatment based.

A total of 455 patients in Australian centers were assigned to either ctDNA-guided care (n=302) or standard care (n=153) following their surgeries. Standard care follows traditional guidelines based on clinicopathological features that are associated with higher cancer risk. If patients in the study’s guided group still had ctDNA present in their blood samples four to seven weeks after surgery, they received one of two kinds of chemotherapy. If tumor DNA was not found, then those patients in the ctDNA-guided group were not treated with chemotherapy.

Of those receiving ctDNA-guided care, physicians were able to not only inform treatment, but actually reduce the number of patients who were treated with chemotherapy without compromising their recurrence-free survival.

"The study’s findings suggest a way to identify which patients can avoid unnecessary chemotherapy, with its potentially serious side effects and its expense. And for those who have undergone chemotherapy or know someone who has, and know what it means, I think this is really great news," said Dr. Cristian Tomasetti, the newly appointed Director of the Center for Cancer Prevention and Early Detection at City of Hope and TGen.

ctDNA can be a useful addition to traditional tissue-based features – like the size of the tumor – to determine risk of recurrence, since tumors themselves are so different from one another.

"For instance, sometimes the potential of a large tumor to be dangerous and invade tissues can actually be lower than a smaller cancer with the right combination of mutations," Dr. Kamel Lahouel, a first author on the paper explained.

In the follow-up 37 months later, patients under standard care were almost twice as likely as patients in the ctDNA-guided group to receive chemotherapy –27.9% compared to 15.3%. Despite the difference in treatment, two-year recurrence-free survival rates were not worse in the guided group (93.5%) compared to the standard care group (92.4%).

"The goal at the beginning of the study was to prove that ctDNA-guided therapy would not lead to worse outcomes than standard care," said Lahouel, "and we ended up with an estimate that is even better than the standard of care guidance. I think that is what is really impressive."

Among the patients in the guided group, those who had the circulating DNA and were treated with chemotherapy had an 86.4% three-year recurrence-free survival rate, compared to 92.5% for those who did not have ctDNA and did not receive chemotherapy.

"We wanted to come up with ways to tell whether therapy was needed, and this technology will also help in the future to determine whether a particular therapy isn’t working, or when we should switch to another therapy, or even when it is OK to stop chemotherapy in a patient. Based on further study we can think about further personalizing treatment with these technologies," said Tomasetti.

Finally, while these findings confirm that certain patients are not likely to need chemotherapy, they also confirm the importance of chemotherapy for those with detectable ctDNA after surgery, Lahouel and Tomasetti noted. In previous studies, scientists found an 80% risk of recurrence in stage II colon cancer patients with detectable ctDNA who did not receive chemotherapy.

This groundbreaking study was led by Dr. Bert Vogelstein and researchers at the Johns Hopkins Kimmel Cancer Center, Dr. Jeanne Tie and researchers at the Peter MacCallum Cancer Centre of the University of Melbourne, Australia, and Drs. Kamel Lahouel, and Cristian Tomasetti, now both at the Translational Genomics Research Institute (TGen) and City of Hope.

Drs. Tomasetti and Lahouel focus on mathematical prediction and advancements in technologies like ctDNA detection, as part of their work with the TGen and City of Hope alliance to transform the diagnosis, treatment and prevention of cancer and other life-threatening diseases.

These exciting results were achieved thanks to new technologies able to find tumor DNA in the blood. The same technologies are also very promising for detecting cancer much earlier.

"All drugs work better in patients with cancers that are detected relatively early, before they have given rise to large metastatic masses. However, new drugs are usually first tested in patients whose cancers are very advanced," said Bert Vogelstein, M.D., Clayton Professor of Oncology, co-director of the Ludwig Center at Johns Hopkins and a Howard Hughes Medical Institute investigator. "We hope that ctDNA analysis will enable testing of new drugs in patients with early-stage cancers and micrometastases, when the new drugs are most likely to save lives."

Research funding support came from The Australian National Health and Medical Research Council (NHMRC), the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, The Conrad R. Hilton Foundation, The Sol Goldman Charitable Trust, John Templeton Foundation, National Institutes of Health (CA62924, CA009071, GM136577 and CA06973) and the Eastern Health Research Foundation (Linda Williams Memorial Grant).

Pfizer Announces Overall Survival Results from Phase 3 PALOMA-2 Trial of IBRANCE® (palbociclib) for the First-Line Treatment of ER+, HER2- Metastatic Breast Cancer

On June 13, 2022 Pfizer Inc. (NYSE:PFE) reported overall survival (OS) results from the Phase 3 PALOMA-2 trial, which evaluated IBRANCE (palbociclib) in combination with letrozole compared to placebo plus letrozole for the first-line treatment of postmenopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) (Press release, Pfizer, JUN 4, 2022, View Source;Metastatic-Breast-Cancer [SID1234615571]). With a median follow-up of 90 months, patients receiving IBRANCE in combination with letrozole had numerically longer OS compared to placebo plus letrozole (median (95% CI) 53.9 months (49.8–60.8) vs median 51.2 months (43.7–58.9)); the results were not statistically significant (Hazard Ratio (HR)=0.956 [95% CI, 0.777–1.177]). The PALOMA-2 trial was designed for a primary endpoint of progression-free survival (PFS) with OS as one of the secondary endpoints. The results will be presented today as an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting (LBA 1003).

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"Forward-Looking Information and Factors That May Affect Future Results"

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"IBRANCE continues to provide substantial benefit as a first-line treatment for adults with HR+, HER2- mBC based on strong progression-free survival data, which formed the basis of its worldwide approvals," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "Interpretation of OS in PALOMA-2 is limited by the large and disproportionate censoring of patients with missing survival data between treatment arms. We remain confident in the compelling benefits that IBRANCE plus endocrine therapy offers to this patient population, which is underscored by data from PALOMA-2 showing delayed time to chemotherapy, maintenance of quality of life and a consistent safety profile. Pfizer continues to invest in expanding the treatment options for people living with metastatic breast cancer."

"IBRANCE transformed the treatment landscape for patients with HR+, HER2- MBC when it was approved in 2015, representing the first new treatment in this patient population in over a decade," said Richard Finn, M.D., Professor of Medicine at the UCLA David Geffen School of Medicine and Jonsson Comprehensive Cancer Center. "PALOMA-2 enrolled a diverse patient population including patients whose disease was first diagnosed in the metastatic stage as well as those with Disease Free Interval (DFI) less than 12 months from adjuvant treatment and those with greater than 12 months following adjuvant treatment. The median survival of over 50 months in this population represents a significant improvement in the natural history of HR+ breast cancer."

PALOMA-2 met its primary endpoint of PFS in 2016 and was published in The New England Journal of Medicine in November 2016. The results demonstrated IBRANCE plus letrozole resulted in an improved median PFS of 24.8 months when compared to 14.5 months with placebo plus letrozole (HR=0.580). The PALOMA-2 trial showed that in addition to substantially delaying progressive disease, IBRANCE as first-line treatment, in combination with letrozole, delayed time to chemotherapy (38.1 months vs 29.8 months; HR, 0.73), while maintaining quality of life with no new identified safety issues.

The OS analysis being presented at ASCO (Free ASCO Whitepaper) included a large proportion of patients with missing survival data (i.e. patients who withdrew consent or were lost to follow-up) and were censored (assumed to be alive) at the time of the analysis: 13% in the treatment arm versus 21% in the control arm. Also of note, 10% of IBRANCE plus letrozole and 2% of placebo plus letrozole patients were still on study treatment at the time of the final analysis. The most common adverse reactions in PALOMA-2 included neutropenia, leukopenia, infections, fatigue and nausea.

IBRANCE continues to be a leader in the CDK4/6 inhibitor class, prescribed to over 450,000 patients across more than 100 countries, and seven out of 10 patients in the U.S. who are prescribed a CDK4/6 inhibitor receiving an IBRANCE prescription.i

About the PALOMA-2 Study

PALOMA-2 is a randomized (2:1), multicenter, multinational, double-blind Phase 3 study designed to assess the efficacy (defined by PFS) and safety of IBRANCE (125 mg orally once daily for three out of four weeks in repeated cycles) in combination with letrozole (2.5 mg once daily continuously) versus letrozole plus placebo as a first-line treatment for postmenopausal women with ER+, HER2- metastatic breast cancer. PALOMA-2 evaluated a total of 666 women from 186 global sites in 17 countries. Patients were to be stratified by site of disease (visceral, non-visceral), by disease-free interval since completion of prior (neo)adjuvant therapy (de novo metastatic, ≤12 months, >12 months), and by the nature of prior (neo)adjuvant anti-cancer treatment received (prior hormonal therapy, no prior hormonal therapy). The primary endpoint was progression-free survival, as assessed by the investigators; secondary endpoints were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety.

About the IBRANCE Real-World Evidence Program

The IBRANCE Real-World Evidence (RWE) program is generating data from multiple studies involving more than 8,000 patients around the world. These studies include diverse patient populations treated in everyday clinical practice and are collecting data related to clinical outcomes, translational data and quality of life endpoints, which complement the data generated from the PALOMA randomized clinical trials. Most recently, Pfizer reported results from a retrospective comparative effectiveness study of 2,888 men and postmenopausal women with HR+, HER2- mBC evaluating IBRANCE in the real-world, first-line setting in combination with aromatase inhibitors (AI) compared to AI alone. Pfizer will continue to share new data from these studies with the scientific community as results become available.

About IBRANCE (palbociclib) 125 mg tablets and capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,ii which are key regulators of the cell cycle that trigger cellular progression.iii,iv In the U.S., IBRANCE is indicated for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.