LOXO-305 for Mantle Cell Lymphoma

(BRUIN-MCL-321 Trial)

Not currently recruiting at 363 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Loxo Oncology, Inc.

Must not be taking: BTK inhibitors, CYP3A4 inducers

Disqualifiers: Bleeding diathesis, Stroke, Cardiovascular, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called pirtobrutinib (LOXO-305) for people with mantle cell lymphoma, a type of blood cancer. The researchers aim to determine pirtobrutinib's effectiveness compared to other FDA-approved drugs. Participants will receive either pirtobrutinib or one of the approved treatments, such as ibrutinib, acalabrutinib, or zanubrutinib. This trial suits those previously treated for mantle cell lymphoma but who still have measurable disease. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial requires stopping ongoing chronic treatment with strong CYP3A4 inhibitors or inducers before starting the study drug. If you are on such medications, you may need to stop them within 3-5 half-lives of the medication before beginning the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pirtobrutinib (LOXO-305) is safe for patients with mantle cell lymphoma. In earlier studies, even patients with extensive prior treatments tolerated pirtobrutinib well. This drug is a BTK inhibitor, which slows the growth of cancer cells.

Reports indicate that the drug is both effective and safe, offering a good balance between benefits and potential side effects. Overall, pirtobrutinib is considered easy for patients to tolerate, making it a promising option for treating this type of blood cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for mantle cell lymphoma that often include BTK inhibitors like ibrutinib, acalabrutinib, or zanubrutinib, LOXO-305, also known as pirtobrutinib, offers a unique approach. LOXO-305 is a next-generation BTK inhibitor, which means it targets the same enzyme but in a more precise way, potentially leading to fewer side effects and greater effectiveness, especially in patients who have developed resistance to other BTK inhibitors. Researchers are excited because this could mean better outcomes for patients who have limited options after their disease becomes resistant to current treatments.

What evidence suggests that LOXO-305 might be an effective treatment for mantle cell lymphoma?

Research has shown that pirtobrutinib, also known as LOXO-305, holds promise in treating mantle cell lymphoma (MCL), particularly for patients who have tried other treatments. In this trial, some participants will receive pirtobrutinib. Studies have found that this drug can lead to long-lasting effects, with the likelihood of the drug remaining effective at 6, 12, and 18 months being 73.6%, 57.1%, and 52.4%, respectively. Additionally, it is generally safe and well-tolerated by patients. Overall, pirtobrutinib appears to be a promising option for treating MCL. ^{1 3 4 5 6}

Who Is on the Research Team?

Patient Advocacy

Principal Investigator

Loxo Oncology, Inc.

Are You a Good Fit for This Trial?

This trial is for people with a blood cancer called mantle cell lymphoma (MCL) who have already tried at least one treatment. They should be relatively healthy, with good organ function and no major bleeding disorders or infections like HIV. People can't join if they've had certain recent treatments, need strong blood thinners, or have serious heart issues.

Inclusion Criteria

My white blood cell count is healthy without needing medication in the past week.

I have been diagnosed with mantle cell lymphoma (MCL).

I have received at least one treatment for my mantle cell lymphoma.

Exclusion Criteria

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

I have a condition that affects how my stomach and intestines absorb food.

I have not had a stem cell transplant or CAR-T therapy in the last 60 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pirtobrutinib or an investigator's choice of BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) for up to 24 months

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if the disease does not progress

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• LOXO-305

Trial Overview The study compares pirtobrutinib (LOXO-305), a new drug, to other approved drugs that target the same protein in MCL cells. Participants will receive their assigned treatment for up to two years or longer if it helps control the disease.

How Is the Trial Designed?

Group I: Arm A (Pirtobrutinib) Experimental Treatment 1 Intervention

Orally

Group II: Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib) Active Control 3 Interventions

Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country.

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

Citations

1. 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.

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/981/499573/Pirtobrutinib-in-Relapsed-Refractory-R-R-Mantle

Pirtobrutinib in Relapsed/Refractory (R/R) Mantle Cell ... Pirtobrutinib continues to demonstrate durable efficacy and a favorable safety profile in heavily pre-treated R/R MCL pts with prior cBTKi therapy.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.00562

Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor ... The 6-, 12-, and 18-month estimated DOR rates were 73.6% (95% CI, 58.0 to 84.2), 57.1% (95% CI, 39.3 to 71.5), and 52.4% (95% CI, 33.9 to 67.9), ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265021018632

ABCL-040: Pirtobrutinib (LOXO-305), a Next-Generation, ... Pirtobrutinib demonstrated promising efficacy in MCL and other NHL pts, was well-tolerated and exhibited a wide therapeutic index.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04662255

NCT04662255 | Study of BTK Inhibitor LOXO-305 Versus ... This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare pirtobrutinib (LOXO-305) to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39109468/

Evaluating pirtobrutinib for the treatment of relapsed or ... Pirtobrutinib is a non-covalent BTK inhibitor that has demonstrated excellent efficacy and safety and represents an important new treatment in ...