Pirtobrutinib for Lymphoma

Recruiting at 37 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Eli Lilly and Company

Disqualifiers: Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

279 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Pirtobrutinib for Lymphoma?

Pirtobrutinib has shown effectiveness in patients with mantle cell lymphoma (MCL) who did not respond to other treatments, achieving a 50% overall response rate in a study. It is also effective for patients with other B-cell cancers who have not responded to previous therapies, with a 62% response rate in a trial. ^{1 2 3 4 5}

Is pirtobrutinib safe for humans?

Pirtobrutinib has been approved for use in certain types of lymphoma, but it can cause side effects like fatigue, muscle pain, diarrhea, swelling, breathing difficulties, pneumonia, and bruising. There are also warnings about infections, bleeding, low blood cell counts, irregular heartbeats, and the risk of new cancers, so ongoing studies are needed to understand its long-term safety. ^{1 2 3 6 7}

How is the drug Pirtobrutinib different from other treatments for lymphoma?

Pirtobrutinib is unique because it is a noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi), which means it can be effective even in patients who have become resistant to other BTK inhibitors. It has shown promise in treating mantle cell lymphoma (MCL) after other treatments have failed, offering a new option for patients with limited choices. ^{1 2 3 8 9}

What is the purpose of this trial?

The master protocol study J2N-MC-JZNY provides a framework to enable the evaluation of the long-term safety and efficacy of pirtobrutinib after completion of clinical studies evaluating pirtobrutinib. The clinical studies that will feed into this master protocol are referred to as originator studies. The master protocol will govern individual study-specific appendices (ISAs) that will represent participants from the individual, completed originator studies. These participants will have the opportunity to enter this study and continue to receive treatment or continue follow-up visits. Overall, the master protocol and the individual ISAs, when combined, define the investigations for this study.

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for patients who are already part of a Lilly sponsored study on pirtobrutinib, which is being tested for lymphoma, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma. Participants must have been receiving or eligible to receive pirtobrutinib in the original studies.

Inclusion Criteria

I am already part of a Lilly study for pirtobrutinib.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue to receive pirtobrutinib as defined in the originator study

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 93 months

Treatment Details

Interventions

• Pirtobrutinib

Trial Overview The trial evaluates long-term safety and effectiveness of pirtobrutinib after initial clinical trials. It's a continuation protocol allowing participants from completed studies to either keep getting treatment or attend follow-up visits to monitor their health over time.

Participant Groups

Group I: JZ01 Pirtobrutinib Experimental Treatment 1 Intervention

Participants receive pirtobrutinib as defined in the originator study (LOXO-BTK-18001/J2N-OX-JZNA). Pirtobrutinib administered orally.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Pirtobrutinib, a noncovalent Bruton tyrosine kinase inhibitor, has shown high response rates in patients with chronic lymphocytic leukemia and mantle cell lymphoma who are resistant to conventional covalent BTK inhibitors, addressing a significant unmet need in this population.

The early studies indicate that pirtobrutinib has a favorable toxicity profile, suggesting it may be suitable for use in combination therapies, and it has recently received accelerated FDA approval for use in mantle cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. Thompson, PA., Tam, CS.[2023]

Pirtobrutinib received accelerated FDA approval for treating adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two prior therapies, showing a 50% overall response rate in a study of 120 patients.

While effective, pirtobrutinib has potential side effects including fatigue, diarrhea, and increased risk of infections and bleeding, necessitating postmarketing studies to further assess its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma. Telaraja, D., Kasamon, YL., Collazo, JS., et al.[2023]

Pirtobrutinib, a novel noncovalent Bruton tyrosine kinase inhibitor, showed a 57.8% overall response rate in patients with relapsed/refractory mantle-cell lymphoma who had previously been treated with covalent BTK inhibitors, indicating its efficacy in a challenging patient population.

The treatment was well tolerated, with only 3% of patients discontinuing due to adverse events, and the most common side effects included fatigue and diarrhea, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma. Wang, ML., Jurczak, W., Zinzani, PL., et al.[2023]

Pilaralisib, a pan-PI3K inhibitor, was found to have an acceptable safety profile in a study of 25 patients with chronic lymphocytic leukemia (CLL) and lymphoma, with common side effects including diarrhea (92%) and pyrexia (52%).

The treatment showed preliminary efficacy, with 50% of CLL patients achieving a partial response and 60% experiencing significant nodal shrinkage, indicating potential for further development in these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma. Brown, JR., Davids, MS., Rodon, J., et al.[2021]

PI3K inhibitors, including idelalisib, copanlisib, and duvelisib, are FDA-approved for treating relapsed and refractory indolent non-Hodgkin lymphoma, demonstrating their efficacy in managing this type of cancer.

While these agents are effective, their use can lead to significant adverse events, especially when combined with other therapies, highlighting the need for careful monitoring and management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI3K Inhibitors and Their Role as Novel Agents for Targeted Therapy in Lymphoma. Sapon-Cousineau, V., Sapon-Cousineau, S., Assouline, S.[2021]

Pirtobrutinib, a noncovalent BTK inhibitor, demonstrated a 73.3% overall response rate in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously failed covalent BTK inhibitor treatments, indicating its efficacy as a new therapeutic option.

The treatment was generally well-tolerated, with only 2.8% of patients discontinuing due to adverse events, and common side effects included infections and bleeding, while serious side effects like hypertension and major hemorrhage were relatively infrequent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia. Mato, AR., Woyach, JA., Brown, JR., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pirtobrutinib: a new hope for patients with BTK inhibitor-refractory lymphoproliferative disorders. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

BTK Inhibitor May Treat Drug-Resistant CLL, SLL. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Transient antagonism of anti-CD20 monoclonal antibodies and PI3K inhibitor idelalisib in DLBCL cell lines. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

PI3K Inhibitors and Their Role as Novel Agents for Targeted Therapy in Lymphoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia. [2023]