Pirtobrutinib for Lymphoma

Recruiting at 36 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, Phase 1b cohort

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

Duration: Long-term

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. It seems to focus on participants continuing from a previous study, so it's best to ask the study team for details.

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 malignancies who have not responded to previous therapies, with a 62% response rate in a trial. ^{1 2 3 4 5}

What is known about the safety of Pirtobrutinib in humans?

Pirtobrutinib has been studied in patients with mantle cell lymphoma and other B-cell malignancies. Common side effects include tiredness, muscle pain, diarrhea, swelling, shortness of breath, pneumonia, and bruising. There are warnings for infections, bleeding, low blood cell counts, irregular heartbeats, and the risk of new cancers. ^{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 alternatives. ^{1 2 3 8 9}

What is the purpose of this trial?

Study J2N-MC-JZ01 (JZ01) is an individual-study appendix (ISA) under master protocol J2N-MC-JZNY, and represents participants from the completed originator study, clinical study LOXO-BTK-18001/J2N-OX-JZNA. Participants in the originator study will have the opportunity to continue their assigned study intervention or continue their follow-up visits by transitioning to this study. This study will evaluate the long-term safety and efficacy of pirtobrutinib.

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 people who have previously been treated for certain blood cancers, including Chronic Lymphocytic Leukemia and various types of Non-Hodgkin's Lymphoma. Participants must be transitioning from a prior study where they were already receiving pirtobrutinib or are in follow-up periods.

Inclusion Criteria

I am currently participating in a clinical trial.

I am in a follow-up period for my condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue receiving pirtobrutinib as defined in the originator study

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 93 months

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Pirtobrutinib

Trial Overview The trial is testing the long-term safety and effectiveness of a drug called Pirtobrutinib in individuals with specific lymphomas and leukemias. It continues treatment or follow-up from an earlier phase of research on this medication.

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]