Oral LOXO-305 for Chronic Lymphocytic Leukemia

Not currently recruiting at 99 trial locations
PA
Overseen ByPatient Advocacy
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called LOXO-305 for individuals with certain blood cancers, such as chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), who have not responded well to standard treatments. Researchers aim to determine if LOXO-305 can benefit these patients, either alone or in combination with other medicines. Individuals with CLL or similar conditions who have tried at least two different treatments, including one targeting specific cancer proteins, might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how LOXO-305 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that pirtobrutinib is generally well-tolerated by individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Earlier studies demonstrated good results with pirtobrutinib, even for those who had previously tried other treatments. Most side effects were mild, with few serious issues reported, suggesting that the treatment is relatively safe, particularly for those who have already used similar drugs.

It is important to note that this trial is in its early stages. The primary goal is to assess the safety and tolerability of pirtobrutinib. Although some safety data is already available, more will be collected to ensure its safety for broader use.12345

Why are researchers excited about this study treatment for chronic lymphocytic leukemia?

Researchers are excited about LOXO-305, also known as pirtobrutinib, because it offers a novel approach to treating chronic lymphocytic leukemia (CLL). Unlike standard treatments like BTK inhibitors, which target a specific part of the cancer cell's signaling pathway, pirtobrutinib is designed to be a highly selective and reversible BTK inhibitor. This unique mechanism allows it to potentially overcome resistance seen with other BTK inhibitors and provide options for patients who have relapsed or have refractory CLL. Additionally, its oral administration makes it convenient for patients, adding to its appeal as a promising new treatment.

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

Research shows that pirtobrutinib, the main focus of this trial, has potential in treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Earlier studies demonstrated its effectiveness for patients who had already tried other treatments, including those who used a covalent BTK inhibitor. In this trial, some participants will receive pirtobrutinib monotherapy, which has previously helped patients live longer without their cancer worsening, especially those who haven't had treatment before. Other participants will receive pirtobrutinib combined with venetoclax, which has resulted in long-lasting periods where the cancer is less active or not detectable. Additionally, the combination of pirtobrutinib, venetoclax, and rituximab has proven very effective, leading to significant improvements in cases where CLL has returned or resisted treatment. These findings highlight the potential of pirtobrutinib, both alone and with other drugs, to manage these challenging conditions.678910

Who Is on the Research Team?

DT

Donald Tsai, MD, PhD

Principal Investigator

Loxo Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
11Treatment groups
Experimental Treatment
Group I: Phase I Dose Escalation (Pirtobrutinib Monotherapy)Experimental Treatment1 Intervention
Group II: Phase 2 (Pirtobrutinib Monotherapy) Cohort 7Experimental Treatment1 Intervention
Group III: Phase 2 (Pirtobrutinib Monotherapy) Cohort 6Experimental Treatment1 Intervention
Group IV: Phase 2 (Pirtobrutinib Monotherapy) Cohort 5Experimental Treatment1 Intervention
Group V: Phase 2 (Pirtobrutinib Monotherapy) Cohort 4Experimental Treatment1 Intervention
Group VI: Phase 2 (Pirtobrutinib Monotherapy) Cohort 3Experimental Treatment1 Intervention
Group VII: Phase 2 (Pirtobrutinib Monotherapy) Cohort 2Experimental Treatment1 Intervention
Group VIII: Phase 2 (Pirtobrutinib Monotherapy) Cohort 1Experimental Treatment1 Intervention
Group IX: Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm BExperimental Treatment3 Interventions
Group X: Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm AExperimental Treatment2 Interventions
Group XI: Phase 1 Dose Expansion (Pirtobrutinib Monotherapy)Experimental Treatment1 Intervention

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

Published Research Related to This Trial

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]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39344587/
Efficacy and Effectiveness Outcomes of Treatments for ...... venetoclax have significantly improved outcomes and achieved durable remission in patients with chronic lymphocytic leukemia (CLL). BTKi/venetoclax-treated ...
NCT06466122 | Pirtobrutinib (LOXO-305) and Venetoclax ...This phase II trial tests how well pirtobrutinib (LOXO-305) and venetoclax works in treating patients with chronic lymphocytic leukemia (CLL) or small ...
Two-Year Pirtobrutinib + Venetoclax for R/R CLLNew study explores 2-year combo of pirtobrutinib + venetoclax ± rituximab for relapsed/refractory CLL. Promising early results.
Efficacy outcomes of treatments for double exposed ...Conclusions: This study underscores the scarcity of clinical data addressing efficacy outcomes in double-exposed CLL/SLL patients. Treatments ...
Fixed-Duration Pirtobrutinib Combined with Venetoclax ...Here, we report the safety and efficacy of fixed-duration pirtobrutinib combined with venetoclax ± rituximab in pts with R/R CLL. Methods: Pts ...
NCT06588478 | A Study Evaluating the Efficacy and Safety ...A Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/​Small Lymphocytic Lymphoma.
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.
Pirtobrutinib Improves PFS in Treatment-Naïve CLL/SLL ...Topline data were announced from a phase 3 trial evaluating pirtobrutinib in treatment-naïve patients with CLL/SLL without 17p deletions.
Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or ...Pirtobrutinib improved PFS and TTNT, and demonstrated favorable tolerability, versus IdelaR/BR in exclusively cBTKi pretreated patients with CLL/SLL.
10.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/37407001/
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.
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