Oral LOXO-305 for Chronic Lymphocytic Leukemia
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.12345Why 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?
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
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Phase 1 Dose Escalation
Dose escalation and determination of maximum tolerated dose (MTD) with pirtobrutinib monotherapy
Phase 1 Dose Expansion
Participants receive the recommended Phase 2 dose of pirtobrutinib
Phase 1b Dose Expansion
Participants receive pirtobrutinib in combination with venetoclax and/or rituximab
Phase 2 Dose Expansion
Participants are enrolled into one of seven cohorts based on tumor histology and prior treatment history
Follow-up
Participants are monitored for safety and effectiveness after treatment
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?
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Treatment groups
Experimental Treatment
Dose Escalation and determination of MTD; multiple dose levels of pirtobrutinib to be evaluated
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.
MZL patients treated with a prior BTK inhibitor-containing regimen.
WM patients treated with a prior BTK inhibitor-containing regimen.
CLL/SLL patients treated with prior therapy, BTK inhibitor naïve.
CLL/SLL patients with no prior therapy.
CLL/SLL patients treated with 2 or more prior regimens, including a BTK inhibitor-containing regimen.
Non-blastoid MCL patients treated with a prior BTK-inhibitor containing regimen.
Relapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax and rituximab
Relapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax
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
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
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
Citations
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 ...
3.
healthtree.org
healthtree.org/cll/community/articles/sponsorstudy-pirtobrutinib-venetoclax-cll-phase-1Two-Year Pirtobrutinib + Venetoclax for R/R CLL
New 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 ...
5.
ashpublications.org
ashpublications.org/blood/article/142/Supplement%201/3269/504047/Fixed-Duration-Pirtobrutinib-Combined-withFixed-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.
8.
hematologyadvisor.com
hematologyadvisor.com/news/pirtobrutinib-improves-pfs-in-treatment-naive-cll-sll-patients/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.
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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