860 Participants Needed

Oral LOXO-305 for Chronic Lymphocytic Leukemia

Recruiting at 94 trial locations
PA
Overseen ByPatient Advocacy
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

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.12345

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

DT

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.
See 6 more

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.
See 17 more

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
11Treatment groups
Experimental Treatment
Group I: Phase I Dose Escalation (Pirtobrutinib Monotherapy)Experimental Treatment1 Intervention
Dose Escalation and determination of MTD; multiple dose levels of pirtobrutinib to be evaluated
Group II: Phase 2 (Pirtobrutinib Monotherapy) Cohort 7Experimental Treatment1 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 6Experimental Treatment1 Intervention
MZL patients treated with a prior BTK inhibitor-containing regimen.
Group IV: Phase 2 (Pirtobrutinib Monotherapy) Cohort 5Experimental Treatment1 Intervention
WM patients treated with a prior BTK inhibitor-containing regimen.
Group V: Phase 2 (Pirtobrutinib Monotherapy) Cohort 4Experimental Treatment1 Intervention
CLL/SLL patients treated with prior therapy, BTK inhibitor naïve.
Group VI: Phase 2 (Pirtobrutinib Monotherapy) Cohort 3Experimental Treatment1 Intervention
CLL/SLL patients with no prior therapy.
Group VII: Phase 2 (Pirtobrutinib Monotherapy) Cohort 2Experimental Treatment1 Intervention
CLL/SLL patients treated with 2 or more prior regimens, including a BTK inhibitor-containing regimen.
Group VIII: Phase 2 (Pirtobrutinib Monotherapy) Cohort 1Experimental Treatment1 Intervention
Non-blastoid MCL patients treated with a prior BTK-inhibitor containing regimen.
Group IX: Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm BExperimental Treatment3 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 AExperimental Treatment2 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 Treatment1 Intervention
Patients to receive the recommended Phase 2 dose of pirtobrutinib

Find a Clinic Near You

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 profile image

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks profile image

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.
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

Ibrutinib Plus Venetoclax for First-line Treatment of Chronic Lymphocytic Leukemia: A Nonrandomized Phase 2 Trial. [2022]
Oral oncolytic treatment for chronic lymphocytic leukemia. [2022]
A literature review of the patent publications on venetoclax - a selective Bcl-2 inhibitor: discovering the therapeutic potential of a novel chemotherapeutic agent. [2019]
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]
Approaches to Chronic Lymphocytic Leukemia Therapy in the Era of New Agents: The Conundrum of Many Options. [2020]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security