Pirtobrutinib for Chronic Lymphocytic Leukemia

Recruiting at 180 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Loxo Oncology, Inc.

Must be taking: Covalent BTK inhibitors

Must not be taking: BTK degraders, Noncovalent BTK inhibitors

Disqualifiers: Richter's transformation, CNS involvement, 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

Duration: Up to 3 years

249 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, Pirtobrutinib, to evaluate its effectiveness and safety for individuals with two types of blood cancer: chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Part 1 of the trial includes participants who have already undergone 1-3 treatments, including a BTK inhibitor. Part 2 involves those who have not yet received treatment but have a specific genetic change (17p deletion). Suitable candidates have been diagnosed with CLL or SLL, require treatment according to established guidelines, and can take the medication orally. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, contributing to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that Pirtobrutinib is likely to be safe for humans?

Research has shown that pirtobrutinib is generally well-tolerated by people with chronic lymphocytic leukemia (CLL). In one study, 29 patients took pirtobrutinib and reported common side effects, such as infections, bleeding, and low white blood cell levels. Most of these side effects were manageable.

Another study found that pirtobrutinib had a better safety profile compared to other treatments, suggesting it might be a safer choice for those who have already tried other CLL medications. Overall, while some side effects exist, research indicates that pirtobrutinib is relatively safe. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for chronic lymphocytic leukemia?

Researchers are excited about Pirtobrutinib for treating Chronic Lymphocytic Leukemia (CLL) because it offers a novel mechanism of action that sets it apart from current treatments like Ibrutinib or Acalabrutinib. Unlike these standard therapies, which target the Bruton's tyrosine kinase (BTK) enzyme to block cancer cell growth, Pirtobrutinib is a next-generation BTK inhibitor that can bind to BTK in a way that is less likely to be affected by mutations that often lead to resistance. This new approach could potentially provide better outcomes for patients whose cancer has become resistant to existing therapies. Additionally, Pirtobrutinib is administered orally, making it a convenient option for patients.

What evidence suggests that Pirtobrutinib might be an effective treatment for chronic lymphocytic leukemia?

Research has shown that pirtobrutinib may effectively treat chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), particularly in patients who have undergone previous treatments. Studies found that pirtobrutinib significantly increased the time patients lived without disease progression. In one study, 62% of patients responded well, with their tumors either shrinking or remaining stable. It also outperformed some standard treatments for both new and previously treated patients. These findings suggest that pirtobrutinib could be a promising option for managing CLL and SLL. Participants in this trial will receive varying doses of pirtobrutinib to assess its effectiveness and safety. ^{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 with a type of blood cancer called CLL/SLL who have tried some treatments but still need help. They should be able to take pills, had up to 3 prior treatments including a specific drug type (BTK inhibitor), and be well enough to do daily activities.

Inclusion Criteria

I have been diagnosed with CLL/SLL according to the latest criteria.

I can take care of myself and am up and about more than half of my waking hours.

I have been treated with a BTK inhibitor.

Exclusion Criteria

I've had severe bleeding from a BTK inhibitor treatment.

I have been treated with specific types of medication for my condition.

My condition has progressed to a more aggressive form of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of three dose levels of Pirtobrutinib orally

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pirtobrutinib

Trial Overview The study tests three doses of Pirtobrutinib in patients whose CLL/SLL has come back or didn't respond after treatment. It checks how well the drug works and its safety over about 3 years.

How Is the Trial Designed?

Group I: Pirtobrutinib Standard Dose-Part 2 Experimental Treatment 1 Intervention

Pirtobrutinib administered orally.

Group II: Pirtobrutinib Dose 3-Part 1 Experimental Treatment 1 Intervention

Pirtobrutinib administered orally.

Group III: Pirtobrutinib Dose 2-Part 1 Experimental Treatment 1 Intervention

Pirtobrutinib administered orally.

Group IV: Pirtobrutinib Standard Dose (Dose 1)-Part 1 Active Control 1 Intervention

Pirtobrutinib administered orally.

Who Is Running the Clinical Trial?

Loxo Oncology, Inc.

Lead Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Eli Lilly and Company

Industry 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

Non-covalent Bruton's tyrosine kinase inhibitors (ncBTKi), like pirtobrutinib, offer a promising alternative for treating chronic lymphocytic leukemia (CLL) due to their reversible binding, which may reduce toxicity and resistance issues associated with covalent inhibitors (cBTKi).

Pirtobrutinib has demonstrated strong safety and preliminary efficacy in clinical trials for CLL, particularly for patients who have developed resistance to previous treatments, highlighting its potential role in addressing unmet needs in CLL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Covalent Bruton's Tyrosine Kinase Inhibitors in the Treatment of Chronic Lymphocytic Leukemia. Montoya, S., Thompson, MC.[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]

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 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 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]

In a meta-analysis of 2456 CLL patients, ibrutinib was found to have a similar risk of anemia, thrombocytopenia, and neutropenia compared to control treatments, indicating a favorable safety profile for these adverse effects.

However, patients treated with ibrutinib experienced significantly higher rates of abdominal issues and diarrhea, suggesting that while it is effective, monitoring for gastrointestinal side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials. Zhou, Y., Lu, H., Yang, M., et al.[2022]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[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. dailynews.ascopubs.org dailynews.ascopubs.org/do/pirtobrutinib-yields-improved-survival-outcomes-patients-relapsed-refractory-cll-sll

Pirtobrutinib Yields Improved Survival Outcomes in ... Key Points: In the phase 3 BRUIN CLL-321 trial, pirtobrutinib demonstrated improved progression-free survival (PFS) and time to next treatment ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41008818/

Pirtobrutinib in Chronic Lymphocytic Leukemia In BRUIN CLL-321, pirtobrutinib achieved an overall response rate (ORR) of 62% and a median progression-free survival (PFS) of 20 months in ...

4. ajmc.com ajmc.com/view/pirtobrutinib-shows-clinically-meaningful-pfs-improvement-in-frontline-cll

Pirtobrutinib Shows Clinically Meaningful PFS ... - AJMC Pirtobrutinib significantly improved progression-free survival in untreated CLL/SLL patients compared to standard chemoimmunotherapy in the ...

5. targetedonc.com targetedonc.com/view/pirtobrutinib-improves-survival-in-treatment-naive-cll-sll

Pirtobrutinib Improves Survival in Treatment-Naive CLL/SLL Pirtobrutinib significantly improved progression-free survival in treatment-naïve CLL/SLL patients compared to bendamustine and rituximab.

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 ... Results: A total of 29 patients received pirtobrutinib. Among these 12 (41.1%) were treated for R/R chronic lymphocytic leukemia (CLL), 11 ...

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

Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or ... Pirtobrutinib improved PFS and TTNT, and demonstrated favorable tolerability, versus IdelaR/BR in exclusively cBTKi pretreated patients with CLL/SLL.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06588478

NCT06588478 | A Study Evaluating the Efficacy and Safety ... The main purpose of Part 1 of this study is to assess the efficacy and safety of 3 dose levels of Pirtobrutinib in participants with chronic lymphocytic ...