Pirtobrutinib vs Ibrutinib for Chronic Lymphocytic Leukemia

(BRUIN-CLL-314 Trial)

Recruiting at 259 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 3

Sponsor: Loxo Oncology, Inc.

Must not be taking: Warfarin, Vitamin K antagonists

Disqualifiers: Richter's transformation, CNS involvement, cardiovascular disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years and 5 months

650 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL. Participants may or may not have already had treatment for their cancer. Participation could last up to six years.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain medications like warfarin, strong CYP3A inhibitors, or if you are using more than 20 mg of prednisone daily.

What data supports the effectiveness of the drug Ibrutinib for treating chronic lymphocytic leukemia?

Ibrutinib has shown effectiveness as a first-line treatment for chronic lymphocytic leukemia in multiple clinical trials, extending the time before the disease becomes active and reducing the growth of cancerous B cells. ^{1 2 3 4 5}

What safety data exists for Ibrutinib and Pirtobrutinib in humans?

Ibrutinib, also known as Imbruvica, has been used to treat chronic lymphocytic leukemia and has shown side effects that differ from traditional chemotherapy. In a study of 616 patients, 41% discontinued due to intolerance, highlighting the importance of managing side effects to maximize its benefits. ^{1 2 6 7 8}

How does the drug Pirtobrutinib differ from Ibrutinib for treating chronic lymphocytic leukemia?

Pirtobrutinib and Ibrutinib are both drugs used to treat chronic lymphocytic leukemia by targeting Bruton's tyrosine kinase (BTK), a protein important for B cell survival. Ibrutinib is an oral covalent inhibitor of BTK, while Pirtobrutinib is a newer option that may offer different benefits or side effects, but specific differences in their effectiveness or safety profiles are not detailed in the provided research. ^{1 5 9 10 11}

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 with CLL/SLL who may need treatment. They should have a certain level of platelets, hemoglobin, and neutrophils; adequate kidney function; and be in fair to good physical condition (ECOG 0-2). It's not for those with uncontrolled autoimmune issues, history of certain lymphomas or leukemia transformations, significant other diseases, active infections like hepatitis B/C or HIV, ongoing inflammatory bowel disease, prior BTK inhibitor use, on strong blood thinners or immune-suppressing drugs.

Inclusion Criteria

My platelet count is at least 50, or 30 if my bone marrow is affected.

My white blood cell count is within the required range.

I have been diagnosed with CLL/SLL and need treatment.

Exclusion Criteria

I am not using any experimental drugs or cancer treatments, except for hormone therapy.

I do not have any ongoing serious infections.

I have a condition that affects how my body absorbs medicine taken by mouth.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pirtobrutinib (LOXO-305) or ibrutinib orally to compare efficacy and safety

3 years and 5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Long-term follow-up

Participants are monitored for overall survival and other long-term outcomes

6 years

Treatment Details

Interventions

• Ibrutinib
• Pirtobrutinib

Trial Overview The study compares Pirtobrutinib (LOXO-305) against Ibrutinib in treating CLL/SLL. Participants will either receive the new drug Pirtobrutinib or the established drug Ibrutinib to see which one works better and is safer. The trial could involve participants for up to six years.

Participant Groups

Group I: Pirtobrutinib Experimental Treatment 1 Intervention

Administered orally.

Group II: Ibrutinib Active Control 1 Intervention

Administered orally.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

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

Findings from Research

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]

Ibrutinib has shown high effectiveness as a first-line treatment for chronic lymphocytic leukemia in real-world settings, with 12-month overall survival rates between 95% and 96% and progression-free survival rates ranging from 89% to 93% across various studies involving 112 to 2033 patients.

The treatment demonstrated a strong response rate, with 71% to 90% of patients responding positively, and a significant majority (91% at 12 months and 87% at 24 months) did not require new treatment, indicating its sustained efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Effectiveness Results Data for First-Line Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. Lee, P., Kistler, KD., Douyon, L., et al.[2023]

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

In a phase 3 trial involving 652 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), zanubrutinib demonstrated superior progression-free survival compared to ibrutinib, with a hazard ratio of 0.65, indicating a significant reduction in the risk of disease progression or death.

Zanubrutinib also had a better safety profile than ibrutinib, resulting in fewer adverse events that led to treatment discontinuation, particularly fewer cardiac events, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. Brown, JR., Eichhorst, B., Hillmen, P., et al.[2023]

Ibrutinib is an effective treatment for chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), showing better outcomes than traditional therapies like chlorambucil and ofatumumab in phase III trials involving elderly and previously-treated patients.

The drug has a good safety profile, although it can cause some adverse effects like bleeding and atrial fibrillation; it is recommended in treatment guidelines for patients with high-risk disease, including those with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Deeks, ED.[2021]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Effectiveness Results Data for First-Line Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. [2022]

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

Ibrutinib Treatment in Early Stage CLL Prolongs Time to Active Disease. [2022]

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

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Ibrutinib and its use in the treatment of chronic lymphocytic leukemia. [2021]

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

Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Ibrutinib: a new frontier in the treatment of chronic lymphocytic leukemia by Bruton's tyrosine kinase inhibition. [2021]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. [2021]

11. Greece pubmed.ncbi.nlm.nih.gov

Comparable Efficacy of Idelalisib Plus Rituximab and Ibrutinib in Relapsed/refractory Chronic Lymphocytic Leukemia: A Retrospective Case Matched Study of the Polish Adult Leukemia Group (PALG). [2021]