Pirtobrutinib for Chronic Lymphocytic Leukemia

(BOSS Trial)

Recruiting at 12 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Acalabrutinib

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Significant cardiovascular disease, HIV, 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: 12

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take strong CYP3A inhibitors or inducers close to starting the study drug. If you're on these, you may need to stop them 1 to 3 weeks before the trial.

What data supports the effectiveness of the drug Pirtobrutinib for treating Chronic Lymphocytic Leukemia?

Pirtobrutinib has shown promising results in patients with chronic lymphocytic leukemia (CLL) who no longer respond to other treatments, like covalent Bruton's tyrosine kinase inhibitors (cBTKis). It has been effective in clinical trials, leading to its approval for a related condition, mantle cell lymphoma, and is being studied further for CLL. ^{1 2 3 4 5}

Is Pirtobrutinib safe for humans?

Pirtobrutinib has been studied for safety in patients with certain types of blood cancers, like mantle cell lymphoma and chronic lymphocytic leukemia. Common side effects include tiredness, muscle pain, diarrhea, swelling, shortness of breath, lung infection, and bruising. There are also warnings about possible infections, bleeding, heart rhythm problems, and other cancers, so ongoing studies are needed to understand its long-term safety. ^{2 3 5 6 7}

How is the drug Pirtobrutinib different from other treatments for chronic lymphocytic leukemia?

Pirtobrutinib is unique because it is a noncovalent (reversible) Bruton's tyrosine kinase inhibitor, which means it can be effective for patients who have become resistant to other covalent BTK inhibitors. This makes it a promising option for those who have limited treatment choices after other therapies have failed. ^{1 2 3 5 7}

What is the purpose of this trial?

To assess the efficacy and safety of pirtobrutinib in participants with CLL/SLL who have progressed on first-line treatment with acalabrutinib.

Eligibility Criteria

This trial is for adults with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma who have seen their disease progress after first-line treatment with Acalabrutinib. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

I can care for myself and am up and about more than 50% of my waking hours.

My organs and bone marrow are working well.

Adequate coagulation, defined as aPTT or PTT and PT or INR not greater than 1.5 × ULN

Exclusion Criteria

I have a bleeding disorder such as hemophilia.

I have not had a stroke or brain bleed in the last 6 months.

Active HBV or HCV infection

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment with Pirtobrutinib

Participants receive pirtobrutinib for up to 24 cycles or until disease progression, unacceptable toxicity, death, or withdrawal of consent

24 months

Monthly visits for the first 6 months, then every 3 months for 12 months, and 2 visits in the last 6 months

Retreatment with Acalabrutinib

Participants who progress on pirtobrutinib receive acalabrutinib for up to 12 cycles or until disease progression, death, intolerance, unacceptable toxicity, or withdrawal of consent

12 months

Monthly visits for the first 6 months, then 2 visits in the last 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

One visit after the treatment phase

Open-label extension (optional)

Participants can continue receiving treatment off-trial if beneficial, in consultation with their physician

Long-term

Treatment Details

Interventions

• Acalabrutinib
• Pirtobrutinib

Trial Overview The study is testing the effectiveness and safety of Pirtobrutinib in patients whose CLL/SLL has worsened despite initial treatment with Acalabrutinib. It's likely a sequential study where Pirtobrutinib follows as a second-line therapy.

Participant Groups

Group I: Pirtobrutinib and Acalabrutinib Experimental Treatment 2 Interventions

Participants will receive dose A of pirtobrutinib starting Cycle 1 Day 1 for up to 24 cycles or until disease progression, unacceptable toxicity, death, or withdrawal of consent. If they progress on pirtobrutinib, a subset will receive dose B of acalabrutinib starting Cycle 1 Day 1 for up to 12 cycles or until disease progression, death, intolerance, unacceptable toxicity, or withdrawal of consent. Those benefiting from treatment will enter the Disease Follow-up period, continuing with pirtobrutinib or acalabrutinib until disease progression, unacceptable toxicity, death, or withdrawal of consent. After 36 months from starting pirtobrutinib, participants can continue receiving treatment off-trial if beneficial, in consultation with their physician.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

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

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

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

3. 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]

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

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Non-Covalent Bruton's Tyrosine Kinase Inhibitors in the Treatment of Chronic Lymphocytic Leukemia. [2023]

6. United States 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. [2022]

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

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