JAYPIRCA ® is a kinase inhibitor indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. ( 1.1 ). This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor. ( 1.2 ).
1.1Mantle Cell Lymphoma
JAYPIRCA ® is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate [see Clinical Studies ( 14.1 )]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
JAYPIRCA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor.
Contraindications
None. None ( 4 ).
Warnings and precautions
Infections: Monitor for signs and symptoms of infection, evaluate promptly, and treat. ( 5.1 ) Hemorrhage: Monitor for bleeding and manage appropriately. ( 5.2 ) Cytopenias: Monitor complete blood counts during treatment. ( 5.3 ) Cardiac Arrythmias: Monitor for symptoms of arrhythmias and manage appropriately. ( 5.4 ) Second Primary Malignancies: Other malignancies have developed, including skin cancers and other carcinomas.
Monitor and advise patients to use sun protection. ( 5.5 ) Hepatotoxicity, Including Drug-Induced Liver Injury: Monitor hepatic function throughout treatment. ( 5.6 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 )
5.1Infections Fatal
and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients treated with JAYPIRCA. Across clinical trials, Grade 3 or higher infections occurred in 25% of 704 patients, most commonly pneumonia (20%), with fatal infections occurring in 5% of patients. Sepsis occurred in 6% of patients and febrile neutropenia in 3.8%. In patients with CLL/SLL, Grade 3 or higher infections occurred in 32% of patients, with fatal infections occurring in 8%.
Opportunistic infections after treatment with JAYPIRCA have included, but are not limited to, Pneumocystis jirovecii pneumonia and fungal infection [see Adverse Reactions ( 6.1 )] . Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients who are at increased risk for infections, including opportunistic infections. Monitor patients for signs and symptoms of infection, evaluate promptly, and treat appropriately.
Based on severity, reduce dose, temporarily withhold, or permanently discontinue JAYPIRCA [see Dosage and Administration ( 2.2 )] .
5.2Hemorrhage Fatal
and serious hemorrhage has occurred with JAYPIRCA. Major hemorrhage (defined as Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 2.6% of 704 patients treated with JAYPIRCA, including gastrointestinal hemorrhage; fatal hemorrhage occurred in 0.3% of patients. Bleeding of any grade, excluding bruising and petechiae, occurred in 16% of patients [see Adverse Reactions ( 6.1 )] . Major hemorrhage occurred in 0.6% of patients taking JAYPIRCA without antithrombotic agents and 2.0% of patients taking JAYPIRCA with antithrombotic agents.
Consider the risks and benefits of antithrombotic agents when co-administered with JAYPIRCA. Monitor patients for signs of bleeding. Based on severity of bleeding, reduce dose, temporarily withhold, or permanently discontinue JAYPIRCA [see Dosage and Administration ( 2.2 )] . Consider the benefit-risk of withholding JAYPIRCA for 3 to 7 days pre- and post-surgery depending upon the type of surgery and risk of bleeding.
5.3Cytopenias
JAYPIRCA can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Across clinical trials, Grade 3 or 4 cytopenias, including decreased neutrophils (27%), decreased platelets (13%), and decreased hemoglobin (11%) developed in patients treated with JAYPIRCA. Grade 4 decreased neutrophils developed in 15% of patients and Grade 4 decreased platelets developed in 6% of patients [see Adverse Reactions ( 6.1 )] .
Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue JAYPIRCA [see Dosage and Administration ( 2.2 )].
5.4Cardiac Arrhythmias
Cardiac arrhythmias, including atrial fibrillation and atrial flutter, were reported in recipients of JAYPIRCA. Atrial fibrillation or flutter were reported in 3.4% of patients, with Grade 3 or 4 atrial fibrillation or flutter reported in 1.6% of 704 patients across clinical trials [see Adverse Reactions ( 6.1 )] . Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred in 0.4% of patients.
Patients with cardiac risk factors, such as hypertension, or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue JAYPIRCA [see Dosage and Administration ( 2.2 )] .
5.5Second Primary Malignancies
Second primary malignancies, including non-skin carcinomas, developed in 9% of 704 patients treated with JAYPIRCA monotherapy across clinical trials. The most frequent malignancy was non-melanoma skin cancer, reported in 4.4% of 704 patients. Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor patients for the development of second primary malignancies.
5.6Hepatotoxicity, Including Drug-Induced Liver Injury
Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including JAYPIRCA. Evaluate bilirubin and transaminases at baseline and throughout treatment with JAYPIRCA. For patients who develop abnormal liver tests after JAYPIRCA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity.
If DILI is suspected, withhold JAYPIRCA. Upon confirmation of DILI, discontinue JAYPIRCA.
5.7Embryo-Fetal Toxicity Based
on findings in animals, JAYPIRCA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of pirtobrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended dose of 200 mg once daily. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with JAYPIRCA and for one week after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )].
Interactions
Strong CYP3A Inhibitors: Avoid concomitant use. If concomitant use is unavoidable, reduce the JAYPIRCA dose. ( 2.4 , 7.1 ) Strong or Moderate CYP3A Inducers: Avoid concomitant use. If concomitant use of moderate CYP3A inducers is unavoidable, increase the JAYPIRCA dose. ( 2.5 , 7.1 ) Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: For substrates where minimal concentration changes may increase the risk of adverse reactions, follow recommendations for co-administration with CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP inhibitors provided in their approved product labeling.
( 7.2 )
7.1Effect of Other Drugs on
JAYPIRCA Strong CYP3A Inhibitors Pirtobrutinib is a CYP3A substrate. Concomitant use of JAYPIRCA with a strong CYP3A inhibitor increased pirtobrutinib systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of JAYPIRCA adverse reactions. Avoid concomitant use of strong CYP3A inhibitors during treatment with JAYPIRCA. If concomitant use of strong CYP3A inhibitors is unavoidable, reduce the JAYPIRCA dosage [see Dosage and Administration ( 2.4 )] .
Strong or Moderate CYP3A Inducers Concomitant use of JAYPIRCA with a strong or moderate CYP3A inducer decreased pirtobrutinib systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce JAYPIRCA efficacy. Avoid concomitant use of JAYPIRCA with strong or moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers is unavoidable, increase the JAYPIRCA dosage [see Dosage and Administration ( 2.5 )] .
7.2Effect of
JAYPIRCA on Other Drugs Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates JAYPIRCA is a P-gp inhibitor, a moderate CYP2C8 and BCRP inhibitor, and a weak CYP2C19 and CYP3A inhibitor. Concomitant use of JAYPIRCA with sensitive P-gp, CYP2C8, BCRP, CYP2C19, or CYP3A substrates increased their plasma concentrations [see Clinical Pharmacology ( 12.3 )], which may increase the risk of adverse reactions related to these substrates for drugs which are sensitive to minimal concentration changes.
Follow recommendations for sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP substrates provided in their approved product labeling.
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary Based
on findings from animal studies, JAYPIRCA can cause fetal harm when administered to a pregnant woman. There are no available data on JAYPIRCA use in pregnant women to evaluate for a drug-associated risk. In an animal reproduction study, administration of pirtobrutinib to pregnant rats during organogenesis resulted in adverse developmental outcomes, including structural abnormalities, altered fetal growth, and embryo-fetal mortality, at maternal exposures approximately 3-times those in patients at the recommended daily dose of 200 mg (see Data).
Advise pregnant women of the potential risk to a fetus. The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data In an embryo-fetal development study in rats, pregnant animals were administered oral doses of pirtobrutinib at up to 500 mg/kg twice daily during the period of organogenesis. Doses ≥ 375 mg/kg twice daily caused decreased fetal body weights and increased incidence of malformations and variations in the urinary tract (including absent or abnormal ureters and kidneys), reproductive tract (malpositioned ovaries and misshapen uterus), and bone (misshapen sternebrae).
At 500 mg/kg twice daily, total resorption was observed. At 375 mg/kg twice daily in rats, the maternal systemic exposures (AUC) were approximately 3 times the human exposure at 200 mg once daily.
Adverse reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions ( 5.1 )] Hemorrhage [see Warnings and Precautions ( 5.2 )] Cytopenias [see Warnings and Precautions ( 5.3 )] Atrial Fibrillation and Atrial Flutter [see Warnings and Precautions ( 5.4 )] Second Primary Malignancies [see Warnings and Precautions ( 5.5 )] Hepatotoxicity, including DILI [see Warnings and Precautions ( 5.6 )] Most common adverse reactions (≥ 30%), including laboratory abnormalities, are fatigue, neutrophil count decreased, platelet count decreased, hemoglobin decreased, leukocytes decreased, lymphocyte count decreased and calcium decreased.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared to rates in the clinical trials of another drug and may not reflect the rates observed in the general patient population. The data in the WARNINGS AND PRECAUTIONS reflect exposure to JAYPIRCA as a single-agent, administered at 200 mg once daily in 704 patients with hematologic malignancies in the BRUIN and the BRUIN-CLL-321 studies.
Among these 704 patients, the median duration of exposure was 12 months; 65% were exposed for at least 6 months and 50% were exposed for at least one year. In this pooled safety population, the most common (≥ 30%) adverse reactions, including laboratory abnormalities, were decreased neutrophil count (54%), decreased hemoglobin (43%), decreased leukocytes (32%), fatigue (31%), decreased platelets (31%), decreased lymphocyte count (31%), and calcium decreased (30%) Mantle Cell Lymphoma BRUIN The safety of JAYPIRCA was evaluated in the BRUIN trial, an open-label, multicohort, single-arm study in patients with previously treated MCL who received a prior BTK inhibitor [see Clinical Studies ( 14.1 ) ] .
The trial required a platelet count ≥ 50 x 10 9 /L, absolute neutrophil count ≥ 0.75 x 10 9 /L, hepatic transaminases ≤ 2.5 times upper limit of normal (ULN), and an ECOG performance status of 0 to 2. The trial excluded patients with active central nervous system (CNS) involvement by lymphoma, significant cardiovascular disease, major bleeding or grade ≥ 3 arrhythmia with a prior BTK inhibitor, prolonged QTc interval, or need for a strong CYP3A inhibitor or inducer or strong P-gp inhibitor.
Patients received JAYPIRCA 200 mg orally once daily until disease progression or unacceptable toxicity (n = 128); 36% were exposed for 6 months or longer and 10% were exposed for at least one year. The median number of prior therapies was 3 (range: 1-9). The median age was 71 years (range: 46 to 88 years) and 80% of patients were male. Race was reported for all patients; 78% were White, 14% were Asian, 2.3% were Black, and 2.3% were Hispanic or Latino.
Serious adverse reactions occurred in 38% of patients who received JAYPIRCA. Serious adverse reactions that occurred in ≥ 2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal adverse reactions within 28 days of the last dose of JAYPIRCA occurred in 7% of patients, most commonly due to infections (4.7%) including COVID-19 (3.1% of all patients).
Adverse reactions led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of JAYPIRCA in 9%. Adverse reactions that resulted in dosage modification in > 5% of patients included pneumonia and neutropenia. Adverse reactions which resulted in permanent discontinuation of JAYPIRCA in > 1% of patients included pneumonia. The most common adverse reactions (≥ 15%), excluding laboratory terms, were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising.
Table 2 summarizes select adverse reactions in BRUIN. Table 2: Adverse Reactions (≥ 10%) in Patients with MCL Who Received JAYPIRCA JAYPIRCA 200 mg once daily N = 128 a Each term listed includes other related terms. b includes 1 fatality from COVID-19 pneumonia. c includes 1 fatality from hemorrhage. Adverse Reactions a All Grades (%) Grade 3-4 (%) General Disorders Fatigue 29
1.6 Edema 18
0.8Fever
13 - Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain 27
3.9Arthritis
or arthralgia 12
0.8Gastrointestinal Disorders Diarrhea
19 - Constipation 13 - Abdominal pain 11
0.8Nausea
11 - Respiratory, thoracic, and mediastinal disorders Dyspnea 17
0.8 Nervous system disorders Peripheral neuropathy 14
0.8Dizziness
10 - Skin and subcutaneous disorders Rash 14 - Vascular disorders Hemorrhage 11 c
3.1 Clinically relevant adverse reactions in < 10% include vision changes, memory changes, headache, urinary tract infection, herpesvirus infection, and tumor lysis syndrome. Table 3 summarizes laboratory abnormalities in BRUIN. Table 3: Select Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients with MCL Who Received JAYPIRCA a The denominator used to calculate the rate varied from 90 to 127 based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory Abnormality JAYPIRCA a 200 mg once daily All Grades (%) Grade 3 or 4 (%) Hematology Hemoglobin decreased 42 9 Platelet count decreased 39 14 Neutrophil count decreased 36 16 Lymphocyte count decreased 32 15 Chemistry Creatinine increased 30
1.6 Calcium decreased 19
1.6 AST increased 17
1.6 Potassium decreased 13
1.6 Sodium decreased 13 - Lipase increased 12
4.4 Alkaline phosphatase increased 11 - ALT increased 11
1.6 Potassium increased 11
0.8Grade
4 laboratory abnormalities in > 5% of patients included neutrophils decreased (10%), platelets decreased (7%), and lymphocytes decreased (6%). Lymphocytosis : Upon initiation of JAYPIRCA, a temporary increase in lymphocyte counts (defined as absolute lymphocyte count increased ≥ 50% from baseline and a post-baseline value ≥ 5,000/μL) occurred in 34% of MCL patients in BRUIN. The median time to onset of lymphocytosis was 1.1 weeks, with 75% of cases occurring within 2.1 weeks, and the median duration was 11 weeks.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma BRUIN The safety of JAYPIRCA was evaluated in the BRUIN trial, an open-label, multicohort, single-arm study in 110 patients with relapsed or refractory CLL/SLL, with 98% having received at least two prior lines of systemic therapy including a covalent BTK inhibitor and a BCL-2 inhibitor [see Clinical Studies ( 14.2 ) ] . The trial required a platelet count ≥ 50 x 10 9 /L, absolute neutrophil count ≥ 0.75 x 10 9 /L, hepatic transaminases ≤ 2.5 times upper limit of normal (ULN), and an ECOG performance status of 0 to 2.
The trial excluded patients with active central nervous system (CNS) involvement by lymphoma, significant cardiovascular disease, major bleeding, uncontrolled or symptomatic arrhythmias, prolonged QTc interval, or need for a strong CYP3A inhibitor or inducer or strong P-gp inhibitor. Patients received JAYPIRCA 200 mg orally once daily until disease progression or unacceptable toxicity (N = 110); 60% were exposed for at least 1 year and 14% were exposed for at least two years.
The median age was 68 years (range: 41 to 88 years) and 67% of patients were male. Race was reported in 110 (100%) patients; of these patients, 89% were White, 4.5% were Black, 1.8% were Asian, and 1.8% were Hispanic or Latino. The median number of prior therapies was 5 (range: 1-11). Serious adverse reactions occurred in 56% of patients who received JAYPIRCA. Serious adverse reactions that occurred in ≥ 5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%).
Fata
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
PIRTOBRUTINIB 50MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
