Efficacy & Study Design | Jaypirca™ (pirtobrutinib)

Jaypirca patient Marc standing with arms folded

^*Not an actual patient

Marc,
in his late 60s, with R/R MCL

Responded well to second-line treatment with a BTK inhibitor, but is now showing early signs of progression
Determined to maintain his current lifestyle for as long as possible

When a covalent BTK inhibitor is no longer an option, treatment options are limited and historically prognosis has been poor.²

After multiple lines of therapy, many patients with R/R MCL have acquired disease characteristics associated with poor prognosis such as advancing age, high MIPI score, and increasing ECOG score, making some therapeutic options inappropriate.^2,3

Do you have patients like Marc?

BTK=Bruton's tyrosine kinase; ECOG=Eastern Cooperative Oncology Group; MCL=mantle cell lymphoma; MIPI=Mantle Cell Lymphoma International Prognostic Index; R/R=relapsed or refractory.

SELECT IMPORTANT SAFETY INFORMATION

Hemorrhage: Fatal and serious hemorrhage occurred in patients with hematologic malignancies treated with Jaypirca (N=583). Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 2.4% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred in 0.2% of patients. Bleeding of any grade, excluding bruising and petechiae, occurred in 14% of patients. 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.

BRUIN evaluated Jaypirca in adult patients with R/R MCL who progressed on or were intolerant to a prior BTKi^1,4†

BRUIN Study Design Chart — The study schema shows the total BRUIN study population, N=583, included patients with hematologic malignancies; the safety population, n=128, consisted of patients with R/R MCL previously treated with BTK inhibitor and the MCL efficacy population, n=120, also assessed patients with R/R MCL previously treated with a BTK inhibitor.

Patients were eligible if they were 18 years or older; had an ECOG status of 0 to 2, had an active hematologic malignancy in need of treatment, and were previously treated. The trial also required patients with a platelet count ≥50 x 10⁹/L, absolute neutrophil count ≥0.75 x 10⁹/L, hepatic transaminases ≤2.5 times ULN.

The primary endpoint was overall response rate. Key secondary endpoints were duration of response, progression-free survival, and overall survival.

Patients received a median of 3 prior lines of therapy (range: 1-9) with 93% having ≥2 prior lines. Phase 2 Dosing of the trial assessed Jaypirca 200 mg once daily until disease progression or unacceptable toxicity. Phase 1 Dosing assessed 25 mg to 300 mg once daily until disease progression or unacceptable toxicity. Intrapatient dose escalation was allowed by protocol.⁴ Efficacy of Jaypirca was based on response as assessed per IRC using 2014 Lugano Criteria.¹

^†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.⁴

Jaypirca was studied in patients with MCL who had progressed on or were intolerant to a BTK inhibitor¹

BTK Pretreated Population chart — **Jaypirca was studied in patients with MCL who had been previously treated with a BTK inhibitor.¹** 83% of patients discontinued their last BTK inhibitor due to refractory or progressive disease and 15% discontinued due to toxicity or other reasons.^#** Patients had a median of 3 prior lines of therapy (range: 1 to 9). In addition to BTK inhibitors, patients were also treated with chemoimmunotherapy (88%), lenalidomide (18%), stem cell transplant (20%), and CAR T-cell therapy (9%).

Due to rounding, numbers presented may not add up to the totals indicated and percentages may not reflect the absolute figures.

^#10% discontinued for toxicity, 5% discontinued for other reasons.¹

^**Other reasons for ending last BTK inhibitor include: completed course of planned treatment, physician decision, patient decision, and other.⁵

BTKi=BTK inhibitor; CAR=chimeric antigen receptor; CNS=central nervous system; HSCT=hematopoietic stem cell transplantation; IRC=independent review committee; ULN=upper limit of normal.

In patients with R/R MCL previously treated with a BTK inhibitor (n=120)^1,6

Overall response rate

CR rate increased from 13% to 16% in the updated analysis^1,6

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.⁷

^††PET-CT scans were utilized in response assessments (in 45% of patients), with the remainder being assessed by CT scans only.⁶

^‡‡ ORR using CT scan-based assessments in all patients was 49% (95% CI: 40, 58) and CR rate was 25%.⁶

^§§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.

A majority of patients responded to Jaypirca or had stable disease⁸

11-month median study follow-up^7¶¶

Disease Control Rate (n=120)⁸

Jaypirca Disease Control Rate — At a median study follow-up of 11 months, the disease control rate with Jaypirca was 73% with a median confidence interval of 65 to 81, complete response rate of 16%, partial response rate of 34%, and stable disease rate of 23%.^7,8¶¶

DCR was not a prespecified endpoint and is a post hoc calculation. DCR is defined as ORR (CR + PR) + SD.^4,8

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.⁹

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.

^¶¶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.

CI=confidence interval; CR=complete response; CT=computed tomography; DCR=disease control rate; PET=positron emission tomography; PR=partial response; SD=stable disease; SPD=sum of the product of diameters.

In patients who responded (n=60)^1,7,10

Duration of response with Jaypirca

11-month median study follow-up^7¶¶

Updated Analysis: DoR (n=60)^{10##***†††}

DoR chart — An updated analysis in 60 patients who responded to Jaypirca. Median duration of response was 17.6 months with a 95% confidence interval of 7.4 to 25.3.¹⁰

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)^1,11
Median DoR was 8.3 months^## (95% CI: 5.7, NE) with a median follow-up for DoR of 7.3 months^{***†††‡‡‡}

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

^¶¶Study follow-up is measured from first dose to last known date to be alive or study exit.
^##Based on Kaplan-Meier estimation.^1,10
^***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.¹¹
^†††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: Grade 3 or 4 cytopenias, including neutropenia, anemia, and thrombocytopenia have developed in patients receiving Jaypirca. In a clinical trial of patients with hematologic malignancies (N=583), Grade 4 neutropenia (13%) and Grade 4 thrombocytopenia (5%) developed. Monitor complete blood counts regularly during treatment; based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Featured Peer Insights

Sparking Discussions about Jaypirca: Appropriate Patients

Join Dr Alan Skarbnik as he discusses which patients may be appropriate for Jaypirca.

0:00–0:01
[Music with a medium beat begins, logo, and Indication animate into view. Music continues for the rest of the video]

0:02–0:05
[Thought Leader introduces the video series while main title screen animates into view]
Welcome to this episode of the Sparking Discussions about Jaypirca video series.

0:06–0:08
[The titles of each episode in the video series animates in, and pill graphic settles on title of this video]

0:09–0:11
[A montage of behind-the-scenes footage with the Thought leader getting ready to film this video is seen]

0:12-0:18
[Thought Leader seen in chair while credentials animate onscreen. Thought Leader begins to summarize what this video is about]
I’m Dr Alan Skarbnik, and today I’ll be going over the type of patients who may benefit from Jaypirca.

0:19–0:32
[Thought leader continues summarizing the video while text animates onscreen]
We’ll start with focusing on how patients with relapsed or refractory MCL may appear in your practice...
…then present the BRUIN study population, before I wrap up with some of my own insights regarding the patient population that Jaypirca is appropriate for.

0:33–0:45
[Thought leader states the Indication statement]
Jaypirca is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, or MCL, after at least two lines of systemic therapy, including a BTK inhibitor.

0:46-1:08
[Thought leader gives safety introduction]
Before we begin our discussion, I'd like to remind you to please refer to the Important Safety Information and the full Prescribing Information regarding warnings and precautions about the use of Jaypirca, like infections, hemorrhage, cytopenias, atrial fibrillation and atrial flutter, second primary malignancies, and embryo-fetal toxicity. A summary of important safety information for Jaypirca will be covered later in this video.

1:09–1:37
[Scene transitions as Hypothetical patient profile graphic appears next to Thought Leader]
Let’s start with a hypothetical patient profile. While females do present with relapsed or refractory MCL, a greater proportion of the patient population are males.

So, this patient is in their late 60s or older with relapsed or refractory MCL
Has initially responded to second-line treatment with a covalent BTK inhibitor, but is showing early signs of progression
And they remain proactive and determined to maintain their current lifestyle as long as possible

1:38-1:56
[Scene shifts to a side-view of Thought Leader as discussion of the appropriate patient continues]
As you know, the clinical challenge in treating a patient at this point is that treatment options become increasingly limited. MCL remains largely incurable and is especially difficult for a patient population that includes characteristics such as advancing age and worsening performance status.

1:57-2:04
[Hypothetical patient profile graphic disappears and transitions to a close-up shot of the Thought Leader]
Now let’s take a look at the BRUIN study, which included patients with relapsed or refractory MCL facing these types of clinical challenges.

2:05-2:58
[BRUIN trial design graphic animates onscreen]
The BRUIN study evaluated the efficacy and safety of Jaypirca in adult patients with relapsed or refractory MCL who progressed on or were intolerant to a prior BTK inhibitor.

BRUIN was a phase 1/2, open-label, single-arm trial that evaluated Jaypirca in 583 adults with previously treated hematologic malignancies. Patients received Jaypirca 200 milligrams once daily until disease progression or unacceptable toxicity.

Although patients with a variety of hematologic malignancies were part of the trial, the MCL efficacy population we’re focusing on here consisted of 120 patients with relapsed or refractory MCL who had all received a prior BTK inhibitor. In the efficacy population, patients received a median of 3 prior lines of therapy, with 93% having had 2 or more prior lines.

2:59-3:22
[BRUIN study graphic is replaced by a graphic of the baseline characteristics of patients in the BRUIN trial]
As you can see here, the 120 patients in the efficacy population had a median age of 71, ranging from 46 to 88. All of these patients had been given a prior covalent BTK inhibitor. It is also important to note that 83% of patients had discontinued their last BTK inhibitor due to refractory or progressive disease.

3:23-3:46
[Medium shot of Thought Leader as a quote animates onscreen]
In summary, patients in the BRUIN trial reflected the kinds of patients with MCL we see in clinical practice. When I consider a patient like this with relapsed or refractory MCL, who has been exposed to prior therapy and remains symptomatic, I’m taking key factors into account when I select their next treatment. I look for things like performance status and age, and choose a treatment that can potentially demonstrate results.

3:47–3:54
[Medium shot of Thought Leader as a new quote animates onscreen]
And from what I have seen so far, Jaypirca is a clinical option I would consider for my patients with relapsed or refractory MCL.

3:55-4:07
[Side-view of Thought Leader transitions to a frontal view while he encourages other physicians to watch this series. The title of the series animates into view]
Thank you for watching this episode of Sparking Discussions about Jaypirca. I invite you to share this episode with your peers and continue this video series to see some of the exciting results from the BRUIN study for yourself.

4:08–4:13
[Summary message animates into view and Thought Leader mentions the select important safety summary]
Stay tuned for the Select Important Safety Summary for Jaypirca.

4:14–8:09
[Voice over of the Indication and Accelerated Approval statement, along with the Select Important Safety Summary for Jaypirca is heard as the safety content scrolls onscreen]

Indication
Jaypirca is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, or 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 benefit in a confirmatory trial.

Select Important Safety Summary for Jaypirca (pirtobrutinib)
Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients treated with Jaypirca. Consider prophylaxis, including vaccinations, in patients at increased risk. Monitor for signs and symptoms of infection, evaluate promptly, and treat appropriately.

Fatal and serious hemorrhage has occurred in Jaypirca-treated patients. Major hemorrhage, including gastrointestinal hemorrhage, occurred. Monitor patients for bleeding and treat appropriately. Consider withholding Jaypirca 3-7 days pre- and post-surgery depending on bleeding risk.

Grade 3 or 4 cytopenias, including neutropenia, anemia, and thrombocytopenia, have developed in patients treated with Jaypirca. Monitor complete blood counts during treatment.

Atrial fibrillation and flutter, including Grade 3 or 4, were reported in Jaypirca treated patients. Patients with cardiac risk factors may be at increased risk. Monitor for signs and symptoms of arrhythmias and manage appropriately.

Second primary malignancies, including skin cancers and other carcinomas, have developed. Monitor, and advise patients to use sun protection.

Jaypirca can cause fetal harm. Advise females of reproductive potential of fetal risk and to use effective contraception. Advise women not to breastfeed.

Serious adverse reactions occurred in 38% and fatal adverse reactions occurred in 7% of patients with MCL. The most common nonhematologic adverse reactions (≥15%) were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 4 laboratory abnormalities in >5% of patients were decreased neutrophils, platelets, and lymphocytes.

Adverse reactions led to dosage reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Adverse reactions resulting in permanent discontinuation in >1% of patients included pneumonia.

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

Avoid concomitant use of Jaypirca with strong CYP3A inhibitors and with strong or moderate CYP3A inducers. If concomitant use with strong CYP3A inhibitors or with moderate CYP3A inducers is unavoidable, modify Jaypirca dosage according to the approved labeling.

Patients aged 65 and older experienced higher rates of Grade 3 and higher adverse reactions and serious adverse reactions compared to patients younger than age 65.

In patients with severe renal impairment, reduce Jaypirca dosage according to approved labeling.

This is not the complete safety information for Jaypirca. Please see full Important Safety Information and links to the Prescribing Information and Patient Information on the surrounding web page.

8:10–8:19
[Scene transition to the sign-off screen with a message to continue the video series, logos, references, and legal language]

Watch the rest of the videos here

Explore the safety data

References:

Jaypirca (pirtobrutinib). Prescribing Information. Lilly USA, LLC.
Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. doi:10.1186/s13045-020-00914-1
Burkart M, Karmali R. Relapsed/refractory mantle cell lymphoma: beyond BTK inhibitors. J Pers Med. 2022;12(3):376. doi:10.3390/jpm12030376
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.
Data on File, Lilly USA, LLC, DOF-PT-US-0008.
Data on File, Lilly USA, LLC, DOF-PT-US-0031.
Data on File, Lilly USA, LLC, DOF-PT-US-0030.
Data on File, Lilly USA, LLC, DOF-PT-US-0032.
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.
Data on File, Lilly USA, LLC, DOF-PT-US-0033.
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, or fungal) and opportunistic infections have occurred in patients treated with Jaypirca. In the clinical trial, Grade ≥3 infections occurred in 17% of 583 patients with hematologic malignancies, most commonly pneumonia (9%); fatal infections occurred in 4.1% of patients. Sepsis (4.5%) and febrile neutropenia (2.9%) occurred. Opportunistic infections after Jaypirca treatment included, but are not limited to, 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 2.4% of 583 patients with hematologic malignancies treated with Jaypirca, including gastrointestinal hemorrhage; fatal hemorrhage occurred in 0.2% of patients. Bleeding of any grade, excluding bruising and petechiae, occurred in 14% of patients. Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (1.7%) 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: Grade 3 or 4 cytopenias, including neutropenia (24%), anemia (11%), and thrombocytopenia (11%) have developed in patients with hematologic malignancies treated with Jaypirca. In a clinical trial, Grade 4 neutropenia (13%) and Grade 4 thrombocytopenia (5%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Atrial Fibrillation and Atrial Flutter: Atrial fibrillation or atrial flutter were reported in 2.7% of patients, with Grade 3 or 4 atrial fibrillation or flutter reported in 1% of 583 patients with hematologic malignancies treated with Jaypirca. 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 6% of 583 patients with hematologic malignancies treated with Jaypirca monotherapy. The most frequent malignancy was non-melanoma skin cancer (3.8%). 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: Based on animal findings, 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 risk to a fetus and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients with Mantle Cell Lymphoma Who Received Jaypirca

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 dose of Jaypirca occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1%).

Dose Modifications and Discontinuations: ARs led to dosage 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 of Jaypirca 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).

All grade ARs with higher frequencies in the total BRUIN population of patients with hematologic malignancies (n=583) were decreased neutrophil count (41%), bruising (20%), diarrhea (20%).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca adverse reactions. Avoid use of strong CYP3A inhibitors during Jaypirca treatment. If concomitant use is unavoidable, reduce Jaypirca dosage according to the 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 the 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: Inform pregnant women of 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 and effects on the breastfed child or on milk production 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, 392 (67%) were ≥65 years of age. 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 (eGFR 15-29 mL/min) increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to the approved labeling. No dosage adjustment is recommended in patients with mild or moderate renal impairment.

PT HCP ISI MCL APP

Please see full Prescribing Information and Patient Information for Jaypirca.

Indication

Jaypirca is a kinase inhibitor 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.

Jaypirca: an approach to BTK inhibition that can help keep positive treatment momentum going for patients like Marc1*

Marc,in his late 60s, with R/R MCL

Do you have patients like Marc?

BRUIN evaluated Jaypirca in adult patients with R/R MCL who progressed on or were intolerant to a prior BTKi1,4†

Jaypirca was studied in patients with MCL who had progressed on or were intolerant to a BTK inhibitor1