A Phase Ia/b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of PRMT5 Inhibitor BGB-58067 Alone and in Combination With Anticancer Agents in Patients With Advanced Solid Tumors

Study Identifier:
BGB-58067-101
CT.gov Identifier:
NCT06589596
EudraCT Identifier:
202452000000
EU Trial (CTIS) Number:
2024-515307-19-00
Study Contact Information:
N/A
Recruiting

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Study Summary

To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency. To evaluate PRMT5 inhibitor in Patients with Non-small cell lung cancer and Solid Tumors

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Phase 1a
    • Read More
  • Drug: Drug: BGB-58067
  • Drug: Drug: BG-89894
  • Drug: Experimental: Phase 1a: BGB-58067 + Standard of Care Combination Therapy Dose Escalation
  • Drug: Drug: Standard of Care Therapy
  • Drug: Experimental: Phase 1b: Dose Expansion and Optimization
  • Drug: In the dose-escalation and safety-expansion phase (phase 1a), sequential cohorts of patients will receive increasing dose levels of BGB-58067 given orally as monotherapy. In the dose-expansion and optimization phase (phase 1b), patients with select tumor types will receive BGB-58067 at the recommended dose(s) for expansion (RDFE[s]).
  • Drug: Intervention/Treatment
  • Drug: Subjects will receive PRMT5 inhibitor
  • Drug: CFDA:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • Participants must sign the ICF and be capable of giving written informed consent Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or Karnofsky Performance Scale (KPS) ≥ 70 Life expectancy ≥ 3 months Evidence of homozygous loss of MTAP or lost MTAP expression in the tumor tissue Able to provide tumor sample to meet the minimum tissue requirement for central MTAP deficiency testing Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose diseases have progressed or recurred after receiving standard systemic therapy or radiotherapy, or for whom standard systemic therapy is not available or tolerated, or would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard treatment in the opinion of the investigator ; participants with advanced, metastatic, or unresectable solid tumors who have not received prior systemic treatment or have received one cycle of standard-of-care therapies will be enrolled in selected cohorts Adequate organ function Patients are ≥18 years of age with pathologically confirmed advanced, metastatic, or unresectable solid tumors who have previously received standard systemic therapy or for whom treatment is not available or tolerated and with evidence of homozygous loss of the MTAP gene or lost MTAP expression in the tumor tissue.
    Exclusion criteria
    • Prior treatment with any methylthioadenosine (MTA)-cooperative PRMT5 inhibitor or methionine adenosyltransferase 2a (MAT2A) inhibitor
    • Active leptomeningeal disease or symptomatic spinal cord compression
    • Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
    • Any malignancy ≤ 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively
    • Significantly impaired pulmonary function
    • Clinically significant infections
    • Serologically active hepatitis B or C infection
    • Known HIV infection. Participants with treated HIV infection may be included in Phase 1b if they meet certain criteria
    • High cardiovascular risk factors
    • QTcF > 470 ms based on the screening triplicate 12-lead ECG records and/or a history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome)
    • Toxicities (because of prior anticancer therapy) that have not recovered to baseline or stabilized
    • Participants who are unable to swallow or with disease/procedure significantly affecting gastrointestinal function
    • Female participants who are pregnant or are breastfeeding
    • Concurrent participation in another therapeutic clinical study (participation in observational or noninterventional studies is allowed)
    • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Irene Moreno
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor