Efficacy
in patients with MCL previously treated with a BTK
inhibitor (n=152)1*
Responses were consistent with longer follow-up1,2
Due to rounding, numbers presented may not add up to the totals indicated and percentages may not reflect the absolute figures.*ORR, the primary endpoint, includes patients with a best response of CR or PR and was assessed by IRC.1CI=confidence interval; CR=complete response; IRC=independent review committee; ORR=overall response rate; PR=partial response.
in patients who responded (n=75)2-4
32 of 72 responders had not progressed or died prior to data cutoff (censored)2
*Based on Kaplan-Meier estimation.1,3 †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.4
‡The primary endpoint was ORR. Efficacy was based on patients with R/R MCL previously treated with a BTK inhibitor.1
§Study follow-up is measured from first dose to last known date to be alive or study exit. ǁDoR 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.
in patients with MCL previously treated with a BTK
inhibitor (n=152)1,3,6
Due to rounding, numbers presented may not add up to the totals indicated and percentages may not reflect the absolute figures. *OS is defined as the time from first dose to death, regardless of disease recurrence. CI=confidence interval; OS=Overall Survival.
in patients who responded (n=75)1,3
Due to rounding, numbers presented may not add up to the totals indicated and percentages may not reflect the absolute figures. *PFS was a secondary endpoint in the BRUIN trial and defined as the number of months from the first dose of study drug to progression or death from any cause. PFS=progression-free survival.
Study Design
*The phase 1 primary outcome was to determine maximum tolerated dose and recommended phase 2 dose; all patients received at least 1 dose of Jaypirca.2†Other includes diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, B-cell prolymphocytic leukemia, hairy cell leukemia, primary CNS lymphoma, and other transformations.2
||||Ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%) in the efficacy population.1‡Patients had confirmed diagnosis of MCL based on local pathology report obtained at time of screening and with no known active CNS involvement; were treated with a prior BTK inhibitor-containing regimen; had at least 1 site of radiographically assessable disease as determined by investigator; and received 1 or more doses of Jaypirca.1
CLL=chronic lymphocytic leukemia; CNS=central nervous system; DoR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; IRC=independent review committee; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; RT=Richter's transformation; SLL=small lymphocytic leukemia; WM=Waldenstrom macroglobulinemia.
Safety
Common adverse reactions (ARs) were mostly Grade 1-2.
aAEs of interest are those that were previously associated with covalent BTK inhibitors. bAggregate of all preferred terms including infection and COVID-19. cAggregate of contusion, bone contusion, ecchymosis, and increased tendency to bruise. dAggregate of all preferred terms including rash. eAggregate of all preferred terms including hemorrhage or hematoma. fAggregate of atrial fibrillation and atrial flutter. gOf 6 total atrial fibrillation and atrial flutter TEAEs, 3 occurred in patients with a prior medical history of atrial fibrillation. In the MCL cohort, treatment-related AEs leading to discontinuation included weight decrease/alopecia/fatigue (1), neutropenia (1), platelet count decreased (1), pneumonitis (1), and cholecystitis (1).
ARs=adverse reactions.
BRUIN SAFETY POPULATION
*See the full Summary of Product Characteristics for information about dose reductions due to adverse reactions. AR=adverse reaction.
Patient Case Study
Dr. Shumilov discusses an MCL patient case study and treatment considerations
Prof. Zinzani discusses an MCL patient case study and treatment considerations
Mechanism of Action
First-and-only approved reversible BTK inhibitor for patients with R/R MCL
In preclinical studies*:
Covalent BTK Inhibitor
Jaypirca: reversible (noncovalent) binding
Jaypirca binds
reversibly
to the BTK protein in the ATP pocket and does not depend on C481. Jaypirca binds reversibly to both wild-type BTK and BTK harboring C481 mutations.1-3
*The clinical relevance of these pharmacologic data has not been determined.
There are no head-to-head trials between Jaypirca and covalent BTK inhibitors comparing
the
clinical significance of their different binding mechanisms.
RECOMMENDED
DOSE IS 200 MG*
Once-Daily Oral Dosing
May be taken
WITH OR
WITHOUT
FOOD†
In a clinical trial,
Jaypirca was allowed
to be coadministered
WITH SELECT ANTICOAGULANTS**,‡
May be taken
WITH GASTRIC
ACID-REDUCING
AGENTS‡
*Jaypirca is also available in 50-mg tablets for use when dose reductions are needed due to
ARs.1
**Except warfarin and vitamin K antagonists, which are not
permitted.1
†Can be taken with a high-fat meal.
‡Dose adjustments are not
required when taking proton pump inhibitors, H2 antagonists, or antacids; no clinically
significant differences in Jaypirca pharmacokinetics were observed when administered
concomitantly with omeprazole, a proton pump inhibitor.1
Consider the
risk/benefit of co-administering antithrombotic agents with Jaypirca and of withholding Jaypirca
3-5 days pre- and post-surgery. Monitor patients for signs of bleeding.1
AR=adverse
reaction; H2=histamine H2.
Dosing
Dose modifications can help manage select ARs1
Dose modification is not recommended for asymptomatic lymphocytosis; asymptomatic lipase increase may not necessarily warrant dose modification.
See the full Prescribing Information for information about dose modifications. For severe renal impairment and for CYP3A inhibitors and inducers, see slides 49-50.
CLL=chronic lymphocytic leukemia; CNS=central nervous system; DoR=duration of response; ECOG
PS=Eastern Cooperative Oncology Group performance status; IRC=independent review committee;
ORR=overall response rate; OS=overall survival; PFS=progression-free survival; RT=Richter's
transformation; SLL=small lymphocytic leukemia; WM=Waldenstrom macroglobulinemia.
*Evaluate
benefit-risk before resuming treatment at the same dose for a Grade 4 nonhematological toxicity.
References:
1. Jaypirca (pirtobrutinib). Summary of Product Characteristics 2. Jaypirca (pirtobrutinib). Prescribing Information. 3. Cohen et al.; ASH 2023. 4. Mato AR, et al. Lancet. 2021; 397(10277)(suppl app.):1-158.5. 5. Mato AR, et al. Lancet. 2021;397(10277):892-901 6. Mato AR, et al. Lancet. 2021;397(10277)(suppl app):119-125. 7. Gu D, et al. J HematolOncol. 2021;14(1):40. 8. Data on File.
Efficacy
In Adult Patients With CLL/SLL After ≥2 Prior Lines,
Including a BTK Inhibitor and a
BCL2 Inhibitor (N=112)2
200 mg daily
The primary endpoint was ORR, which included patients with a best response of PR or better and was assessed by IRC using 2018 iwCLL criteria.
CI=confidence interval, PR=Partial Response, PR-L=Partial Response with Lymphocytosis.
In Patients With CLL/SLL Who Responded (N=81)2
*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.
†The primary endpoint was ORR. Efficacy was based on 128 patients with CLL/SLL who were previously treated with ≥2 prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor.1,9
‡Based on Kaplan-Meier estimation.1
In Patients With CLL/SLL Who Responded (N=81)2
PFS was a secondary endpoint in the BRUIN trial and defined as the number of months
from the first dose of study drug to progression or death from any cause.
PFS=progression-free survival.
*As determined by IRC assessment.
In Adult Patients With CLL/SLL After ≥2 Prior Lines,
Including a BTK Inhibitor and a BCL2 Inhibitor (N=128)2
*OS is defined as the time
from first dose to death, regardless of disease recurrence.
CI=confidence interval; OS=Overall Survival.
Study Design
*Phase 1 dosing: 25-300 mg once daily until disease progression
or
unacceptable toxicity; intrapatient dose escalation was allowed by protocol.2
†Trial excluded patients with active CNS involvement by lymphoma, allogeneic HSCT, or CAR T-cell therapy within 60 days, significant cardiovascular disease, major bleeding, grade ≥3 arrhythmia with prior BTK inhibitors in patients with MCL, uncontrolled or symptomatic arrhythmias in patients with CLL/SLL, prolonged QTc interval, or need for strong CYP3A inhibitor or inducer or strong P-gp inhibitor.1,3
‡Ibrutinib (97%), acalabrutinib (9%), and zanubrutinib (0.9%) in the CLL/SLL efficacy population.
DoR=duration of response. ECOG=Eastern Cooperative Oncology Group. ORR=overall response rate. OS=overall survival. PFS=progression-free survival.
Safety
In adults with CLL/SLL previously treated with a BTK inhibitor and BCL2 inhibitor2
aARs of interest are those that were previously associated with covalent BTK inhibitors. bAggregate of neutropenia and neutrophil count decreased. cNeutropenia at baseline for BCL2i-E (n=128) was 27.3. dAggregate of all preferred terms including infection and COVID-19. eAggregate of contusion, ecchymosis, increased tendency to bruise and oral contusion. fAggregate of all preferred terms including rash. gAggregate of all preferred terms including hemorrhage or hematoma. hAggregate of atrial fibrillation and atrial flutter. iOf the 13 total afib/aflutter TEAEs in the prior BTKi safety population (n=282), 6 occurred in patients with a prior medical history of atrial fibrillation.
NCCN Guidelines 02.2025
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) - Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma – Version 3.2024 — March 26, 2024
Onkopedia Guidelines, September 2024
Onkopedia – onkopedia leitlinien - Chronic lymphocytic leukemia (CLL) - ICD-10: C91.1, Stand: September 2024,
Chronic lymphocytic leukemia (CLL) — Onkopedia
ESMO Guidelines,
2024
Eichhorst, B., et al. "ESMO Clinical Practice Guideline interim update on new targeted therapies in the first line and at relapse of chronic lymphocytic leukaemia." Annals of Oncology 35.9 (2024): 762-768.
Mechanism of Action
First-and-only approved reversible BTK inhibitor for patients with R/R CLL/SLL
In preclinical studies*:
Covalent BTK Inhibitor
Jaypirca: reversible (noncovalent) binding
Jaypirca binds
reversibly
to the BTK protein in the ATP pocket and does not depend on C481. Jaypirca binds reversibly to both wild-type BTK and BTK harboring C481 mutations.1-3
*The clinical relevance of these pharmacologic data has not been determined.
There are no head-to-head trials between Jaypirca and covalent BTK inhibitors comparing
the
clinical significance of their different binding mechanisms.
RECOMMENDED
DOSE IS 200 MG*
Once-Daily Oral Dosing
May be taken
WITH OR
WITHOUT
FOOD†
In a clinical trial,
Jaypirca was allowed
to be coadministered
WITH SELECT ANTICOAGULANTS**,‡
May be taken
WITH GASTRIC
ACID-REDUCING
AGENTS‡
*Jaypirca is also available in 50-mg tablets for use when dose reductions are needed due to
ARs.1
**Except warfarin and vitamin K antagonists, which are not
permitted.1
†Can be taken with a high-fat meal.
‡Dose adjustments are not
required when taking proton pump inhibitors, H2 antagonists, or antacids; no clinically
significant differences in Jaypirca pharmacokinetics were observed when administered
concomitantly with omeprazole, a proton pump inhibitor.1
Consider the
risk/benefit of co-administering antithrombotic agents with Jaypirca and of withholding Jaypirca
3-5 days pre- and post-surgery. Monitor patients for signs of bleeding.1
AR=adverse
reaction; H2=histamine H2.
Dosing
Dose modifications can help manage select ARs1
Dose modification is not recommended for asymptomatic lymphocytosis; asymptomatic lipase increase may not necessarily warrant dose modification.
See the full Prescribing Information for information about dose modifications. For severe renal impairment and for CYP3A inhibitors and inducers, see slides 49-50.
CLL=chronic lymphocytic leukemia; CNS=central nervous system; DoR=duration of response; ECOG
PS=Eastern Cooperative Oncology Group performance status; IRC=independent review committee;
ORR=overall response rate; OS=overall survival; PFS=progression-free survival; RT=Richter's
transformation; SLL=small lymphocytic leukemia; WM=Waldenstrom macroglobulinemia.
*Evaluate
benefit-risk before resuming treatment at the same dose for a Grade 4 nonhematological toxicity.
References:
1. Jaypirca (pirtobrutinib). Prescribing Information. 2. Woyach et al.; ASH 2023. 3. Cohen et al.; ASH 2023.
ניתן
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תרופתי" שנמצא בדף הבית של
אתר משרד הבריאות:
https://www.health.gov.il המפנה לטופס המקוון לדיווח על תופעות לוואי, או ע"י כניסה
לקישור: https://sideeffects.health.gov.il
לדיווח
על פגם איכות ו/או תופעות לוואי ניתן ליצור קשר עם החברה בטלפון שמספרו: 09-9606234
Jaypirca® Therapeutic Indications:
• Jaypirca™ as monotherapy is indicated for the treatment of adult patients with relapsed or
refractory (R/R) MCL who have been previously treated with a BTK inhibitor.
• Jaypirca™
is indicated for the treatment of adult patients with CLL/SLL who have received at least two
prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
For full information see the Israeli MOH-approved PI
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