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MCL Efficacy

Jaypirca may be appropriate for patients with R/R MCL who initially responded to second-line BTK inhibitors but are showing signs of progression1

In patients with R/R MCL previously treated with a BTK inhibitor (n=120)

Overall response rate1,2

Responses were consistent with longer follow-up1,2


CR rate increased from 13% to 16% in the updated analysis1,2

The primary endpoint in the initial analysis was ORR, which included patients with a best response of CR or PR and was assessed by IRC using 2014 Lugano criteria.1

The updated post-hoc analysis (median 11-month study follow-up) has not been reviewed by the FDA and is not included in the Prescribing Information for Jaypirca.3

*PET-CT scans were utilized in response assessments (in 45% of patients), with the remainder being assessed by CT scans only.2

ORR using CT scan-based assessments in all patients was 49% (95% CI: 40, 58) and CR rate was 25%.2

PET-CT scans were utilized in response assessments (in 41% of patients), with the remainder being assessed by CT scans only.1

§ORR using CT scan-based assessments in all patients was 48% (95% CI: 38, 57) and CR rate was 13%.1

||Study follow-up is measured from first dose to last known date to be alive or study exit.

Due to rounding, percentages may not reflect the absolute figures.

BTK=Bruton's tyrosine kinase; CI=confidence interval; CR=complete response; CT=computed tomography; IRC=independent review committee; MCL=mantle cell lymphoma; ORR=overall response rate; PET=positron emission tomography; PR=partial response; R/R=relapsed or refractory.

SELECT IMPORTANT SAFETY INFORMATION

Hemorrhage: Fatal and serious hemorrhage occurred in patients with hematologic malignancies treated with Jaypirca. Major hemorrhage occurred (3%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred in 17%. Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca and of withholding Jaypirca for 3-7 days pre- and post-surgery. Monitor patients for signs of bleeding and reduce dose, temporarily withhold, or permanently discontinue Jaypirca, based on severity.

A majority of patients responded to Jaypirca or had stable disease4

11-month median study follow-up


Disease Control Rate (n=120)4

DCR was not a prespecified endpoint and is a post-hoc calculation. DCR is defined as ORR (CR + PR) + SD.4,5

SD is defined as a <50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extranodal sites by radiologic assessment per Lugano response criteria.6

In a single-arm trial without a control arm for comparison as would be provided by a randomized trial, the interpretation and clinical relevance of a best overall response of SD are not clear, and no conclusions can be drawn. It is not possible to determine whether SD is a result of natural disease progression or treatment with Jaypirca.

Due to rounding, percentages may not reflect the absolute figures.

Study follow-up is measured from first dose to last known date to be alive or study exit.

DCR=disease control rate; SD=stable disease; SPD=sum of the product of diameters.

In patients who responded (n=60)1,3,7

Duration of response with Jaypirca


11-month median study follow-up3#

Updated Analysis: DoR (n=60)7**††‡‡

Updated post-hoc analysis has not been reviewed by the FDA and is not included in the Prescribing Information for Jaypirca.

  • 32 of 60 responders had not progressed or died prior to data cutoff (censored)7,8
  • Median DoR was 17.6 months** (95% CI: 7.4, 25.3) with a median follow-up for DoR of 9.2 months7††‡‡§§

Initial Analysis (n=60)1

  • At 6 months, 65% of responders were still responding (95% CI: 50, 77)1
  • 36 of 60 responders had not progressed or died prior to data cutoff (censored)1,8
  • Median DoR was 8.3 months** (95% CI: 5.7, NE) with a median follow-up for DoR of 7.3 months1††‡‡§§

#Study follow-up is measured from first dose to last known date to be alive or study exit.
**Based on Kaplan-Meier estimation.1,7
††DoR was calculated for patients who achieved a response of PR or better and was defined as the time from first evidence of response to progression or death from any cause.8
‡‡The primary endpoint was ORR. Efficacy was based on patients with R/R MCL previously treated with a BTK inhibitor.1
§§DoR follow-up is measured from initial response to progression, death, or last adequate disease assessment in the absence of progression or death. Participants were censored at progression or death, according to the reverse Kaplan-Meier method.

NE=not estimable.

SELECT IMPORTANT SAFETY INFORMATION

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly during treatment; based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

BRUIN evaluated Jaypirca in adult patients with R/R MCL who progressed on or were intolerant to a prior BTKi1,5||||


||||Ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%) in the efficacy population.1
¶¶Trial excluded patients with significant cardiovascular disease, major bleeding, or grade ≥3 arrhythmia with prior BTKi, prolonged QTc interval, or need for strong CYP3A inhibitor or inducer or strong P-gp inhibitor.1
##Not all patients in the safety population met criteria to be evaluated for efficacy.
***Patients with active CNS lymphoma or allogeneic HSCT or CAR T-cell therapy within 60 days were excluded.1
†††The phase 1 primary outcome was to determine maximum tolerated dose and recommended phase 2 dose. All patients received at least one dose of Jaypirca.5

BTKi=BTK inhibitor; CAR=chimeric antigen receptor; CNS=central nervous system; ECOG=Eastern Cooperative Oncology Group; HSCT=hematopoietic stem cell transplantation; ULN=upper limit of normal.

References:

  1. Jaypirca. Prescribing Information. Lilly USA, LLC.
  2. Data on File, Lilly USA, LLC, DOF-PT-US-0031.
  3. Data on File, Lilly USA, LLC, DOF-PT-US-0030.
  4. Data on File, Lilly USA, LLC, DOF-PT-US-0032.
  5. Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901.
  6. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059-3067.
  7. Data on File, Lilly USA, LLC, DOF-PT-US-0033.
  8. Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277)(suppl app):119-125.

Important Safety Information

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal infections occurred in 4.4%. Sepsis (6%) and febrile neutropenia (4%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 3% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred in 17%. Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients who received Jaypirca. In a clinical trial of patients with hematologic malignancies, atrial fibrillation or flutter were reported in 3.2% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.5%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.5%). 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.

Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients. The most frequent malignancy was non-melanoma skin cancer (4.6%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats during organogenesis caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of potential fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥20%) ARs in the BRUIN pooled safety population of patients with hematologic malignancies (n=593) were decreased neutrophil count (46%), decreased hemoglobin (39%), fatigue (32%), decreased lymphocyte count (31%), musculoskeletal pain (30%), decreased platelet count (29%), diarrhea (24%), COVID-19 (22%), bruising (21%), cough (20%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients. Serious ARs occurring 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 ARs within 28 days of last Jaypirca dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations: ARs led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation in >1% of patients included pneumonia.

ARs (all Grades %; Grade 3-4 %) in ≥10% of Patients: fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -), peripheral neuropathy (14; 0.8), cough (14; -), rash (14; -), fever (13; -), constipation (13; -), arthritis/arthralgia (12; 0.8), hemorrhage (11; 3.1), abdominal pain (11; 0.8), nausea (11; -), upper respiratory tract infections (10; 0.8), dizziness (10; -).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), 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; 0.8). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Serious ARs occurred in 56% of patients. Serious ARs occurring in ≥5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%). Fatal ARs within 28 days of last Jaypirca dose occurred in 11% of patients, most commonly due to infections (10%), including sepsis (5%) and COVID-19 (2.7%).

Dose Modifications and Discontinuations: ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dose reductions in >1% included neutropenia; treatment interruptions in >5% of patients included pneumonia, neutropenia, febrile neutropenia, and COVID-19; permanent discontinuation in >1% of patients included second primary malignancy, COVID-19, and sepsis.

ARs (all Grades %; Grade 3-4 %) in ≥10% of Patients: fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), dyspnea (22; 2.7), hemorrhage (22; 2.7), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9), arthritis/arthralgia (19; 1.8), rash (19; 0.9), peripheral neuropathy (16; 3.6), dizziness (15; -), fall (14; 0.9), constipation (14; -), insomnia (14; -), upper respiratory tract infections (13; 2.7), second primary malignancy (13; 2.7), renal insufficiency (12; 6), hypertension (12; 5), neurological changes (12; 2.7), mucositis (12; 0.9), decreased appetite (12; -), respiratory tract infection (11; 1.8), supraventricular tachycardia (10; 5).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥20% of Patients: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), platelet count decreased (30; 15), sodium decreased (30; -), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), lipase increased (21; 7), alkaline phosphatase increased (21; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid use of strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dosage according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dosage according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Special Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk is unknown. Advise women not to breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Severe renal impairment increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to approved labeling.

PT HCP ISI COMBO DEC2023

Please see full Prescribing Information and Patient Information for Jaypirca.

Indications

Jaypirca is a kinase inhibitor indicated for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

Jaypirca is also indicated for the treatment of adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.

These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.