Oral LOXO-305 for Chronic Lymphocytic Leukemia

Recruiting at 94 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Loxo Oncology, Inc.

Must not be taking: Warfarin, Strong CYP3A4 inhibitors

Disqualifiers: Pregnancy, HIV, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

860 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any investigational agents or anticancer therapies at least 14 days before starting the study, and certain monoclonal antibody treatments must be stopped 4 weeks prior. You cannot take any concurrent systemic anticancer therapy during the trial.

What makes the drug LOXO-305 unique for treating chronic lymphocytic leukemia?

LOXO-305 is a novel treatment for chronic lymphocytic leukemia that may offer a different mechanism of action compared to existing therapies like Bruton tyrosine kinase inhibitors and Bcl-2 inhibitors, which are often used in combination. While specific details about LOXO-305's mechanism are not provided, its development suggests it could provide an alternative option for patients who may not respond to or tolerate current treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing pirtobrutinib, a tablet taken by mouth, in patients with certain types of blood cancers who haven't responded to or can't tolerate usual treatments. The medication works by blocking a protein that cancer cells need to grow. The study aims to find the best dose and see how well it works.

Research Team

Donald Tsai, MD, PhD

Principal Investigator

Loxo Oncology

Eligibility Criteria

This trial is for patients with certain blood cancers like CLL/SLL or NHL who have not responded well to standard treatments or are intolerant to them. They should be in a stable condition (ECOG 0-2), able to take oral medication, and willing to use effective birth control. People can't join if they've had major surgery recently, are pregnant, on warfarin therapy, have uncontrolled infections or other serious health issues, or have been treated with pirtobrutinib before.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

I can take medication by mouth.

I have CLL/SLL, WM, or NHL and cannot tolerate at least 2 treatments or have had a BTK inhibitor.

Exclusion Criteria

I do not have any ongoing serious infections.

I haven't had a heart attack or uncontrolled heart issues in the last 6 months.

I have been treated with pirtobrutinib before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Dose escalation and determination of maximum tolerated dose (MTD) with pirtobrutinib monotherapy

Up to 24 months

Phase 1 Dose Expansion

Participants receive the recommended Phase 2 dose of pirtobrutinib

Up to 24 months

Phase 1b Dose Expansion

Participants receive pirtobrutinib in combination with venetoclax and/or rituximab

Up to 24 months

Phase 2 Dose Expansion

Participants are enrolled into one of seven cohorts based on tumor histology and prior treatment history

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LOXO-305

Trial Overview The study is testing LOXO-305 (pirtobrutinib) given orally. It's an open-label Phase 1/2 trial meaning everyone gets the drug and both safety and effectiveness will be studied. The participants include those who've failed previous therapies including BTK inhibitors unless it was used as first-line treatment.

Participant Groups

Group I: Phase I Dose Escalation (Pirtobrutinib Monotherapy) Experimental Treatment 1 Intervention

Dose Escalation and determination of MTD; multiple dose levels of pirtobrutinib to be evaluated

Group II: Phase 2 (Pirtobrutinib Monotherapy) Cohort 7 Experimental Treatment 1 Intervention

Defined as CLL/SLL or NHL not otherwise specified in Cohorts 1 through 6, inclusive of CLL/SLL, Richter's transformation, or low grade NHL with transformation, blastoid MCL, and patients with history of CNS involvement or primary CNS lymphoma. In the event the Sponsor electively closes Cohorts 2-4 prior to completion, patients with CLL/SLL who are ineligible to participate in or unable to access late phase studies of pirtobrutinib may be eligible to enroll in this cohort Diffuse large B-cell lymphoma (DLBCL) is excluded. MCL without prior BTK inhibitor treatment is excluded. Patients enrolling to Cohort 7 must have received one or more prior therapies or have no available approved therapy with demonstrated clinical benefit with the exception of untreated Richter's transformation, which is allowed.

Group III: Phase 2 (Pirtobrutinib Monotherapy) Cohort 6 Experimental Treatment 1 Intervention

MZL patients treated with a prior BTK inhibitor-containing regimen.

Group IV: Phase 2 (Pirtobrutinib Monotherapy) Cohort 5 Experimental Treatment 1 Intervention

WM patients treated with a prior BTK inhibitor-containing regimen.

Group V: Phase 2 (Pirtobrutinib Monotherapy) Cohort 4 Experimental Treatment 1 Intervention

CLL/SLL patients treated with prior therapy, BTK inhibitor naïve.

Group VI: Phase 2 (Pirtobrutinib Monotherapy) Cohort 3 Experimental Treatment 1 Intervention

CLL/SLL patients with no prior therapy.

Group VII: Phase 2 (Pirtobrutinib Monotherapy) Cohort 2 Experimental Treatment 1 Intervention

CLL/SLL patients treated with 2 or more prior regimens, including a BTK inhibitor-containing regimen.

Group VIII: Phase 2 (Pirtobrutinib Monotherapy) Cohort 1 Experimental Treatment 1 Intervention

Non-blastoid MCL patients treated with a prior BTK-inhibitor containing regimen.

Group IX: Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm B Experimental Treatment 3 Interventions

Relapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax and rituximab

Group X: Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm A Experimental Treatment 2 Interventions

Relapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax

Group XI: Phase 1 Dose Expansion (Pirtobrutinib Monotherapy) Experimental Treatment 1 Intervention

Patients to receive the recommended Phase 2 dose of pirtobrutinib

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

Three new oral small molecule inhibitors—ibrutinib, idelalisib, and venetoclax—have been approved for chronic lymphocytic leukemia (CLL) treatment in the last four years, showing excellent efficacy.

These inhibitors have different toxicity profiles, which is important for tailoring treatment, especially in older patients, and raises questions about how to best sequence their use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to Chronic Lymphocytic Leukemia Therapy in the Era of New Agents: The Conundrum of Many Options. Jain, N., Thompson, P., Ferrajoli, A., et al.[2020]

References

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

Ibrutinib Plus Venetoclax for First-line Treatment of Chronic Lymphocytic Leukemia: A Nonrandomized Phase 2 Trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Oral oncolytic treatment for chronic lymphocytic leukemia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A literature review of the patent publications on venetoclax - a selective Bcl-2 inhibitor: discovering the therapeutic potential of a novel chemotherapeutic agent. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

R-etodolac (SDX-101) and the related indole-pyran analogues SDX-308 and SDX-309 potentiate the antileukemic activity of standard cytotoxic agents in primary chronic lymphocytic leukaemia cells. [2015]

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

Approaches to Chronic Lymphocytic Leukemia Therapy in the Era of New Agents: The Conundrum of Many Options. [2020]