Pirtobrutinib for Lymphoma

Recruiting at 39 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety and effectiveness of pirtobrutinib for individuals with lymphoma, a type of blood cancer. It includes those already participating in an earlier study with pirtobrutinib, whether still receiving treatment or in follow-up stages. Participants must not have been part of the initial Phase 1b group of the previous study. As a Phase 4 trial, this study involves an FDA-approved treatment, aiming to understand its benefits for a broader patient population.

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 is the safety track record for pirtobrutinib?

Research has shown that pirtobrutinib is generally well-tolerated by patients. One study found that common mild side effects include high blood pressure, bruising, nausea, vomiting, diarrhea, anemia (a deficiency of healthy red blood cells), and rash, each affecting about 10% of patients. Although these side effects were mostly mild, detailed long-term safety information is still being gathered. As a Phase 4 treatment, pirtobrutinib has already been approved for use in other conditions, indicating a strong safety record. However, ongoing studies like this one are essential to understand its safety over a longer period. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Pirtobrutinib is unique because it targets a key player in lymphoma cells called Bruton's tyrosine kinase (BTK). Unlike traditional treatments like chemotherapy or other BTK inhibitors, pirtobrutinib is designed to bind reversibly, which may help overcome resistance that some patients develop to current therapies. Researchers are excited about its potential to offer a more effective and lasting response for patients, especially those who have not responded well to existing treatments. Additionally, being an oral medication, it offers a convenient alternative to infusions, making treatment easier for patients to manage.

What is the effectiveness track record for pirtobrutinib in treating lymphoma?

Research has shown that pirtobrutinib, the investigational treatment in this trial, works well for certain types of lymphoma. In patients with follicular lymphoma that has returned or not responded to treatment, pirtobrutinib helped 52.1% of them, with benefits lasting an average of 10.2 months. It also shows promise for mantle cell lymphoma (MCL) that has come back or is hard to treat, although limited real-world data exists. For chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), pirtobrutinib has been effective in patients who have tried other treatments before. These findings suggest that pirtobrutinib could be a valuable treatment option for people with these types of lymphoma. ^{2 3 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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, 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2300696

Pirtobrutinib after a Covalent BTK Inhibitor in Chronic ... In this trial, pirtobrutinib showed efficacy in patients with heavily pretreated CLL or SLL who had received a covalent BTK inhibitor.

2. ashpublications.org ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024014975/546861/Pirtobrutinib-a-Highly-Selective-Non-covalent

Pirtobrutinib, a Highly Selective, Non-covalent (Reversible ... Pirtobrutinib demonstrates efficacy in relapsed/refractory follicular lymphoma with an ORR of 52.1% and median DOR of 10.2 months.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11106640/

Outcomes of pirtobrutinib for relapsed/refractory mantle cell ... Pirtobrutinib shows promising response rates in heavily pretreated MCL patients according to the approval study, but the real‐world data are scarce.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00166

Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or ... At the prespecified final OS analysis, 18-month OS was 73.4% (95% CI, 63.9 to 80.7) in the pirtobrutinib group and 70.8% (95% CI, 60.9 to 78.7) ...

5. hematologyadvisor.com hematologyadvisor.com/news/pirtobrutinib-improves-pfs-in-treatment-naive-cll-sll-patients/

Pirtobrutinib Improves PFS in Treatment-Naïve CLL/SLL ... Findings showed patients treated with pirtobrutinib had a statistically significant and clinically meaningful improvement in PFS compared with ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6778/528384/The-Real-World-Safety-and-Tolerability-of

The Real-World Safety and Tolerability of Pirtobrutinib Among ... Other common grade I/II AEs included hypertension (10.3%), bruising (10.3%), nausea/ vomiting (10.3%), diarrhea (10.3%), anemia (6.9%), and rash ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7513

Long-term safety with ≥12 months of pirtobrutinib in ... However, the long-term safety and tolerability of pirtobrutinib has not yet been reported. Here we report the clinical safety in pts with long- ...

8. prnewswire.com prnewswire.com/news-releases/phase-3-results-for-lillys-jaypirca-pirtobrutinib-in-covalent-btk-inhibitor-pre-treated-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-to-be-presented-at-the-2024-ash-annual-meeting-302326603.html

Phase 3 results for Lilly's Jaypirca® (pirtobrutinib) in ... Results from BRUIN CLL-321 show Lilly's pirtobrutinib reduced the risk of disease progression or death by 46% compared to idelalisib plus rituximab or ...