LOXO-305 for Chronic Lymphocytic Leukemia

(BRUIN CLL-321 Trial)

Not currently recruiting at 312 trial locations

Overseen By Seo-Hyun Kim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Loxo Oncology, Inc.

Must be taking: BTK inhibitors

Must not be taking: Warfarin, CYP3A4 inhibitors

Disqualifiers: Richter's transformation, CNS involvement, 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 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LOXO-305 for individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously tried a BTK inhibitor. The researchers aim to compare the effectiveness of LOXO-305 with other treatments, such as idelalisib plus rituximab or bendamustine plus rituximab. Suitable candidates are those previously treated for CLL or SLL and still seeking effective options. Participation may last several years if the treatment successfully prevents disease progression. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are currently on strong CYP3A4 inhibitors or inducers, or if you require therapeutic anticoagulation with warfarin or another Vitamin K antagonist.

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

Research has shown that LOXO-305, also known as pirtobrutinib, is generally safe and well-tolerated by patients. It remains effective even when other treatments fail due to certain mutations, offering hope for patients who haven't found success with other options.

Previous studies indicate that most patients did not experience serious side effects, suggesting that LOXO-305 is generally safe for those with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Although this treatment is still under investigation, its presence in the later stages of clinical trials indicates strong evidence supporting its safety. Prospective trial participants may find this information reassuring regarding the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

LOXO-305 is unique because it targets chronic lymphocytic leukemia (CLL) in a new way. Unlike standard treatments that often involve chemotherapy or other types of inhibitors, LOXO-305 works by selectively inhibiting the BTK protein, a key player in CLL cell survival, without affecting other similar proteins. This selective action might reduce side effects and improve effectiveness compared to current options like ibrutinib or acalabrutinib. Researchers are excited about its potential to provide a more targeted and potentially safer alternative for patients with CLL.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Studies have shown that pirtobrutinib (LOXO-305), which participants in this trial may receive, works well for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have already tried other treatments. One study found that patients with CLL or SLL who had previously used a BTK inhibitor experienced good results with pirtobrutinib. Research indicates that pirtobrutinib can help prevent disease progression. Additionally, over 70% of patients reported that their quality of life remained stable or improved while using it. Overall, these findings suggest that pirtobrutinib could be a promising option for people with this condition. ^{1 3 4 6 7}

Who Is on the Research Team?

Marisa Hill, MD

Principal Investigator

Loxo Oncology, Inc.

Are You a Good Fit for This Trial?

This trial is for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have had previous treatment including a BTK inhibitor. They should be in fairly good health, with specific blood counts and organ function levels meeting the study's criteria. People with certain heart diseases, active infections like hepatitis or HIV, recent live vaccinations, or known allergies to the drugs being tested cannot join.

Inclusion Criteria

I can perform daily activities with little to no assistance.

AST and ALT ≤ 3.0 x upper limit of normal (ULN)

Total bilirubin ≤ 1.5 x ULN

Exclusion Criteria

I have an active, uncontrolled immune system disorder affecting my blood cells.

I have a serious heart condition.

Known hypersensitivity, including anaphylaxis, to any component or excipient of LOXO-305. For patients planned to receive idelalisib, known hypersensitivity, including anaphylaxis, to any component or excipient of idelalisib. For patients planned to receive bendamustine, known hypersensitivity, including anaphylaxis, to any component or excipient of bendamustine

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either LOXO-305 or investigator's choice of idelalisib plus rituximab or bendamustine plus rituximab. Treatment continues until disease progression, discontinuation, or unacceptable toxicity.

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 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

• Bendamustine
• Idelalisib
• LOXO-305
• Rituximab

Trial Overview The study compares LOXO-305 against two other treatments: Idelalisib plus Rituximab or Bendamustine plus Rituximab. Patients will receive one of these treatments based on random assignment and could participate for up to four years if their disease doesn't worsen.

How Is the Trial Designed?

Group I: Arm A - Pirtobrutinib Experimental Treatment 1 Intervention

Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.

Group II: Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab Active Control 3 Interventions

Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m\^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m\^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m\^2 every 4 weeks (Q4W) or 70 mg/m\^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m\^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m\^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

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

Recent advancements in treatment options for chronic lymphocytic leukemia (CLL) include novel targeted therapies like obinutuzumab and ofatumomab, which are effective and well-tolerated, especially for elderly patients or those with other health issues.

Ibrutinib and idelalisib show excellent efficacy in CLL, particularly for patients with 17p deletions, while the newly FDA-approved venetoclax offers promising results for those with relapsed or refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the armamentarium for chronic lymphocytic leukemia: A review of novel agents in the management of chronic lymphocytic leukemia. Marini, BL., Samanas, L., Perissinotti, AJ.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39344587/

Efficacy and Effectiveness Outcomes of Treatments for ... This study highlights the limited clinical data on efficacy outcomes for double-exposed CLL/SLL patients. Pirtobrutinib, lisocabtagene maraleucel, and a ...

2. 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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04666038

NCT04666038 | Study of LOXO-305 (Pirtobrutinib) Versus ... This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (Arm A) to investigator's choice of either idelalisib plus rituximab or bendamustine ...

4. 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 ...

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6535/504584/Patient-Reported-Outcomes-PROs-Among-Patients-with

Patient-Reported Outcomes (PROs) Among Patients with ... Overall, consistent with the favorable safety profile of pirtobrutinib, HRQoL and symptoms were stable or improved for over 70% of patients with pretreated R/R ...

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

Pirtobrutinib in Chronic Lymphocytic Leukemia Results: Pirtobrutinib demonstrates activity against BTK resistance mutations with a favorable safety profile, partly due to high kinase ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/325/500040/Pirtobrutinib-in-Post-cBTKi-CLL-SLL-30-Months

Pirtobrutinib in Post-cBTKi CLL/SLL: ~30 Months Follow-up ... Pirtobrutinib continues to demonstrate promising and durable efficacy in pts with post-cBTKi heavily pretreated CLL/SLL. ORR was high regardless of prior BCL2i ...