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CLL Efficacy

Progression-Free Survival
Time to Next Treatment
CLL-321 Trial
BRUIN Phase 1/2 Trial

In a Phase 3 trial of patients with R/R CLL previously treated with a cBTKi

Jaypirca demonstrated statistically significant improvement in Median PFS1,2

Primary Analysis Median PFS1 (median follow up of 6.6 months):

aBased on Kaplan-Meier estimation.

bBased on stratified Cox proportional hazards model.

cInvestigator's choice of IdR or BR

d2-sided p-value based on stratified log-rank test

CI=confidence interval; HR=hazard ratio; IdR/BR=idelalisib plus rituximab or bendamustine plus rituximab; IRC=independent review committee; iwCLL=International Workshop for Chronic Lymphocytic Leukemia; PFS=progression-free survival.

Updated Analysis Median PFS2,3 (median follow up of 18.4 months):

Updated non-prespecified analysis results from CLL-321 were not error-controlled or adjusted for multiplicity. Conclusions of a statistically significant difference in PFS must be based only on the prespecified, error-controlled, Primary Analysis of the ITT population.

aBased on Kaplan-Meier estimation.

bBased on stratified Cox proportional hazards model.

cInvestigator's choice of IdR or BR.

At an updated analysis (median follow-up of 19.8 months), IRC-assessed ORR* was 48.7% (95% CI 39.5, 58.1) in the Jaypirca arm and 38.7% (95% CI 29.9, 48.0) in the investigator's choice arm.1

CI=confidence interval; HR=hazard ratio; IdR/BR=idelalisib plus rituximab or bendamustine plus rituximab; IRC=independent review committee; iwCLL=International Workshop for Chronic Lymphocytic Leukemia; ORR=overall response rate; PFS=progression-free survival; PR=partial response.

*ORR was defined as PR or better confirmed on two full post-baseline tumor assessments.4

CLL Patient Characteristics arrowRight Arrow Right

SELECT IMPORTANT SAFETY INFORMATION

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) 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 for signs of bleeding and reduce dose, temporarily withhold, or permanently discontinue Jaypirca, based on severity.

In a Phase 3 trial of patients with R/R CLL previously treated with a cBTKi

Median time to next treatment was 24 months for patients in the Jaypirca treatment arm 2

Median Time to Next Treatment (median study follow-up of 17.2 months)2

Time to next treatment (TTNT) is defined as time from the date of randomization to the date of initiation of the subsequent anticancer therapy (including crossover), or death due to any cause, whichever occurs first. Per protocol, continuation on Jaypirca after progression was allowed if the patient was tolerating study treatment and deriving ongoing clinical benefit, based on the opinion of the Investigator.2,4

The recommended Jaypirca dose is 200 mg once daily until disease progression or unacceptable toxicity.1

  • TTNT was a secondary endpoint based on investigator assessment and was not included in the prespecified statistical testing procedure. The data presented are descriptive and conclusions cannot be drawn from these data.4
  • TTNT is subject to variability in treatment practice and can be subjective based on investigator interpretation of individual patient and disease characteristics.4

cBTKi=covalent Bruton's tyrosine kinase inhibitor; CI=confidence interval; CLL=chronic lymphocytic leukemia; IdR/BR=idelalisib plus rituximab or bendamustine plus rituximab; R/R=relapsed or refractory; TTNT=time to next treatment.

SELECT IMPORTANT SAFETY INFORMATION

Cytopenias: 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. Grade 4 decreased neutrophils (15%) 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.

CLL-321 is the only randomized Phase 3 trial where all patients with R/R CLL were previously treated with a covalent BTKi1,2

CLL-321 was a randomized, open-label, active-controlled Phase 3 study1,2

Primary endpoint1

  • Progression-free survival (PFS) as assessed by IRC using 2018 iwCLL criteria

Key secondary endpoint2

  • Overall survival (OS)

Key inclusion criteria1,2

  • Confirmed CLL/SLL requiring treatment per 2018 iwCLL criteria
  • Prior treatment with a cBTKi required, prior BCL-2 inhibitor permitted
  • ECOG PS 0-2
  • Platelet count ≥50 x 109/L, absolute neutrophil count ≥ 0.75 x 109/L, an estimated creatinine clearance ≥30 mL/min

Key exclusion criteria1

  • Significant CV disease including uncontrolled or symptomatic arrhythmias
  • Major bleeding on a prior cBTKi

Stratification factors1

  • 17p deletion status (yes/no)
  • Prior treatment with venetoclax (yes/no)

Of the 238 patients randomized, 119 were assigned to Jaypirca monotherapy, 82 to IdR, and 37 to BR.1

aIdelalisib 150 mg orally twice daily until disease progression or unacceptable toxicity, in combination with 8 infusions of a rituximab product (375 mg/m2 intravenously on Day 1 of Cycle 1, followed by 500 mg/m2 every 2 weeks for 4 doses and then every 4 weeks for 3 doses), with a 28-day cycle length1

bBendamustine 70 mg/m2 intravenously (Day 1 and 2 of each 28-day cycle), in combination with a rituximab product (375 mg/m2 intravenously on Day 1 of Cycle 1, then 500 mg/m2 on Day 1 of subsequent cycles), for up to 6 cycles1

Per protocol, patients with confirmed PD by IRC were permitted to crossover from the IdR/BR arm to the Jaypirca arm if they met eligibility criteria for treatment by iwCLL 2018. Of the 119 patients in the investigator’s choice arm, 50 crossed over to receive Jaypirca therapy.1,2

Of the 238 patients randomized in the CLL-321 trial, median number of prior lines of therapy was 3 (range: 1 to 13): 51% received prior BCL-2 inhibitor therapy.1

BCL-2=B-cell lymphoma 2; BTK=Bruton’s tyrosine kinase; BTKi=Bruton’s tyrosine kinase inhibitor; CLL=chronic lymphocytic leukemia; CNS=central nervous system; CV=cardiovascular; ECOG PS=Eastern Cooperative Oncology Group performance status; IR/BR=idelalisib plus rituximab or bendamustine plus rituximab; IRC=independent review committee; iwCLL=International Workshop on Chronic Lymphocytic Leukemia; PD=progressive disease; PO=orally; R/R=relapsed or refractory.

The Phase 1/2 BRUIN trial studied 100+ patients previously treated with a covalent BTKi and a BCL2i to evaluate the clinical benefit of Jaypirca in R/R CLL1

In adults with R/R CLL/SLL after ≥2 prior lines, including a BTKi and BCL2i (n=108), Jaypirca delivered a robust response1,5

72% ORR for Jaypirca in R/R CLL/SLL

aORR, the primary endpoint, includes patients with a best response of PR or better and was assessed by IRC using 2018 iwCLL Critera1,5

In patients with R/R CLL/SLL who responded (n=78), Jaypirca delivered a durable response:1,5

12.2 months median DoR for Jaypirca in R/R CLL/SLL

aBased on Kaplan-Meier estimation. Estimated median follow-up was 15.7 months1.

bDoR was defined as time from first evidence of response to progression or death from any cause.5

Efficacy was evaluated in an open-label, single-arm Phase 1/2 trial of Jaypirca monotherapy (200 mg once daily until disease progression or unacceptable toxicity) in adult patients with R/R CLL/SLL after ≥2 prior lines, including a BTKi and BCL2i. Patients in the efficacy and safety populations had an ECOG PS 0-2 and had received a median of 5 prior lines of therapy.1

BCL2i=B-cell lymphoma 2 inhibitor; BTKi=Bruton’s tyrosine kinase inhibitor; CLL/SLL=chronic lymphocytic leukemia/small lymphocytic lymphoma; DoR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; IRC=independent review committee; iwCLL=International Workshop for Chronic Lymphocytic Leukemia; ORR=overall response rate; PR=partial response; R/R=relapsed or refractory.

Discover once-daily dosing

Dosing details

References:

  1. Jaypirca. Prescribing Information. Lilly USA, LLC.
  2. Sharman JP, Munir T, Grosicki S, et al. Phase III trial of pirtobrutinib versus idelalisib/rituximab or bendamustine/rituximab in covalent Bruton tyrosine kinase inhibitor pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma (BRUIN CLL-321). J Clin Oncol. 2025;43(22):2538-2549. doi:10.1200/JCO-25-00166
  3. Data on File. DOF-PT-US-0048. Lilly USA, LLC.
  4. Loxo Oncology, Inc. CLINICAL PROTOCOL LOXO-BTK-20020: A phase 3 open-label, randomized study of LOXO-305 versus investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab in BTK inhibitor pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma (BRUIN-CLL-321). Protocol No. LOXO-BTK-20020 (J2N-OX-JZNN). Published June 14, 2024. Accessed June 24, 2025. https://ascopubs.org/action/downloadSupplement?doi=10.1200/JCO-25-00166&file=protocol_JCO-25-00166.pdf
  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):Suppl append. doi:10.1016/S0140-6736(21)00224-5

Important Safety Information

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. Across clinical trials, Grade ≥3 infections occurred (25%), most commonly pneumonia (20%); fatal infections (5%), sepsis (6%), and febrile neutropenia (3.8%) 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 for signs and symptoms, evaluate, and treat. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider withholding Jaypirca 3-7 days pre- and post-surgery based on surgery type and bleeding risk.

Cytopenias: 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. Grade 4 decreased neutrophils (15%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients taking Jaypirca. Across clinical trials, atrial fibrillation or flutter were reported in 3.4% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.6%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.4%). Cardiac risk factors such as hypertension or previous arrhythmias may increase risk. Monitor and manage signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea). Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Across clinical trials, second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients, most frequently non-melanoma skin cancer (4.4%). 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.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. 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. If DILI is confirmed, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm. Administration of pirtobrutinib to pregnant rats 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 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 (≥30%) ARs in the pooled safety population of patients with hematologic malignancies (n=704) were decreased neutrophil count (54%), decreased hemoglobin (43%), decreased leukocytes (32%), fatigue (31%), decreased platelets (31%), decreased lymphocyte count (31%), calcium decreased (30%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients, with pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%) occurring in ≥2% of patients. Fatal ARs within 28 days of last 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 Due to ARs: Dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%) and Select Laboratory Abnormalities (≥10%) (all Grades %; Grade 3-4 %): hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), fatigue (29; 1.6), musculoskeletal pain (27; 3.9), calcium decreased (19; 1.6), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), AST increased (17; 1.6), pneumonia (16; 14), bruising (16; -), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), ALT increased (11; 1.6), potassium increased (11; 0.8), alkaline phosphatase increased (11; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma from Single-Arm and Randomized Controlled Clinical Trials

Serious ARs occurred in 47-56% of patients across clinical trials. Serious ARs in ≥5% of patients in the single-arm trial were pneumonia (18%), COVID-19 (9%), sepsis (7%), febrile neutropenia (7%). Serious ARs in ≥3% of patients in the randomized controlled trial were pneumonia (21%), COVID-19 (5%), sepsis (3.4%). Fatal ARs within 28-30 days of last Jaypirca dose occurred in 8-11% of patients, most commonly due to infections (7- 10%), including sepsis (5%), COVID-19 (2.7-5%), and pneumonia (3.4%).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 3.6-10%, treatment interruption in 42-51%, and permanent discontinuation of Jaypirca in 9-17% of patients. Permanent discontinuation in >1% of patients included second primary malignancy, pneumonia, COVID-19, neutropenia, sepsis, anemia, and cardiac arrhythmias.

Most common ARs and Select Laboratory Abnormalities (≥20%) (all Grades %, Grade 3-4 %)--in a randomized controlled trial: neutrophil count decreased (54; 26), hemoglobin decreased (45; 10), platelet count decreased (37; 17), pneumonia (28; 16), ALT increased (25; 1.8), creatinine increased (25; -), calcium decreased (23; 0.9), sodium decreased (22; 0.9), bilirubin increased (21; 0.9), upper respiratory tract infections (21; 0.9); in a single-arm trial: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), platelet count decreased (30; 15), sodium decreased (30; -), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), dyspnea (22; 2.7), hemorrhage (22; 2.7), lipase increased (21; 7), alkaline phosphatase increased (21; -), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

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

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

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

Use in Specific 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. Presence of pirtobrutinib in human milk is unknown. Advise women to use effective contraception and to not 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: Because severe renal impairment increases pirtobrutinib exposure, reduce Jaypirca dose in these patients according to approved labeling.

PT HCP ISI MCL_CLL Q42025

Please see full Prescribing Information and Patient Information for Jaypirca.

Indications

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.

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. 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 trial benefit in a confirmatory trial.