Pirtobrutinib vs BR for Leukemia

(BRUIN CLL-313 Trial)

Not currently recruiting at 182 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Loxo Oncology, Inc.

Must not be taking: Warfarin, Vitamin K antagonists

Disqualifiers: Richter's transformation, 17p deletion, 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 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how well the new drug, pirtobrutinib, works compared to a combination of bendamustine (a chemotherapy drug) and rituximab (an immunotherapy drug) in treating chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). These cancers affect the blood and lymph nodes. The study seeks to identify which treatment is more effective and safer for those who have not yet received any treatment. Individuals with a confirmed diagnosis of CLL/SLL, who have not been treated before and have normal kidney function, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to advancing cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use other investigational or anticancer therapies while participating. If you are on warfarin or another Vitamin K antagonist, you will need to stop those.

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

Research has shown that pirtobrutinib has been tested for safety in people with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). One study showed promising results but also highlighted some risks. Specifically, 24% of patients experienced serious infections, with pneumonia being the most common at 14%. This indicates that while pirtobrutinib can be effective, many patients might face serious side effects.

Bendamustine and rituximab, often used together for CLL, are generally effective but can also cause side effects, such as low blood cell counts and an increased risk of infections.

Both treatments have demonstrated effectiveness but come with the risk of side effects. These factors are important to consider when deciding to join a trial involving these drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment for leukemia, which often includes the intravenous combination of bendamustine and rituximab, Pirtobrutinib offers a unique approach. Pirtobrutinib is administered orally and functions as a potent BTK inhibitor, which is different from the standard regimen that utilizes chemotherapeutic and immunotherapy mechanisms. Researchers are excited about Pirtobrutinib because it specifically targets the BTK pathway, potentially leading to fewer side effects and offering a novel option for patients who may not respond well to existing treatments.

What evidence suggests that this trial's treatments could be effective for CLL/SLL?

This trial will compare Pirtobrutinib with the combination of Bendamustine and Rituximab (BR) for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Research has shown that Pirtobrutinib, which participants in this trial may receive, has promising results, helping 62% of patients by shrinking or eliminating their cancer, with an average of about 20 months before the cancer started to grow again. In comparison, the combination of Bendamustine and Rituximab, another treatment option in this trial, has been effective for CLL, with 59% of patients seeing their cancer shrink or disappear, and an average time of about 15.2 months before the cancer grew again. Both treatments work well, but Pirtobrutinib might provide longer-lasting results. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

This trial is for untreated patients with CLL/SLL who need therapy. They must have a certain level of blood cells and organ function, no severe allergies to the drugs being tested, no active hepatitis B/C or HIV, and not be on other cancer treatments or recent live vaccines.

Inclusion Criteria

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

Platelets ≥75 x 10⁹/L (≥50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin ≥8 g/dL, and absolute neutrophil count ≥0.75 x 10⁹/L

My organs are working well.

Exclusion Criteria

My cancer has a 17p deletion.

I have active hepatitis B or C.

I do not have any ongoing serious infections.

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 Bendamustine plus Rituximab

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Pirtobrutinib
• Rituximab

Trial Overview The study compares Pirtobrutinib (LOXO-305) against Bendamustine plus Rituximab in treating CLL/SLL. Participants will receive one of these treatments randomly and their health outcomes will be monitored for up to five years.

How Is the Trial Designed?

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

Pirtobrutinib administered orally

Group II: Arm B (BR) Active Control 2 Interventions

Bendamustine plus rituximab administered intravenously (IV)

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

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in European Union as Ribomustin for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma

Approved in Canada as Levact for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in Japan as Bendamustine hydrochloride for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

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/PMC6029555/

Efficacy of bendamustine and rituximab as first salvage ... In 78 CLL patients who had received 1-3 previous lines of treatment, the BR combination was associated with a 59% ORR with a median PFS of 15.2-months.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03609593

Study Details | NCT03609593 | Bendamustine/rituximab ... The purpose of this study is to determine the efficacy of bendamustine and rituximab (BR) followed by venetoclax for 12 months. The total time on therapy is 15 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9868021/

Safety and Efficacy of Bendamustine and Rituximab (BR) ... Combinations of lower dose fludarabine and cyclophosphamide with a higher dose of rituximab have resulted in high overall and complete response rates [7, 8].

4. haematologica.org haematologica.org/article/view/8525

Efficacy of bendamustine and rituximab as first salvage ... We performed an observational study on the efficacy of ben-damustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL).

5. ashpublications.org ashpublications.org/blood/article/123/19/2944/32655/Randomized-trial-of-bendamustine-rituximab-or-R

Randomized trial of bendamustine-rituximab or R-CHOP/R ... The overall response rates for BR and R-CHOP/R-CVP were 97% and 91%, respectively (P = .0102). Incidences of vomiting and drug-hypersensitivity reactions were ...

6. 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 ...

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

Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or ... Pirtobrutinib has shown promising safety and efficacy in the phase 1/2 BRUIN study in R/R patients with CLL/SLL, including patients previously ...

8. 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 ...

9. 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 ... The median follow-up time was 6 (IQR 3-10.5) months. The median duration of treatment was 4 (2-8.5) months. Ten (34.5%) patients had disease ...

10. prnewswire.com prnewswire.com/news-releases/lillys-jaypirca-pirtobrutinib-the-first-and-only-approved-non-covalent-reversible-btk-inhibitor-met-its-primary-endpoint-in-a-head-to-head-phase-3-trial-versus-imbruvica-ibrutinib-in-cllsll-302515393.html

Lilly's Jaypirca (pirtobrutinib), the first and only approved ... In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal ...