This is an open-label, multicenter, first-in-human dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 alone, in combination with BG-89894 (discontinued), and in combination with standard of care therapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.
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
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
Sequential
BGB-58067
DrugPlanned doses administered on specified days per protocol.
BG-89894
DrugPlanned doses administered on specified days per protocol.
Standard of Care Therapy
DrugAdministered in accordance with relevant local guidelines and/or prescribing information.
Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events
Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.
Phase 1a: Number of Participants with Adverse Events that meet Dose-Limiting Toxicity (DLT) criteria
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy
MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached. Note: BGB-58067 + BG-89894 combination has been discontinued.
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy
RDFE of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be determined based upon the MTD or MAD. Note: BGB-58067 + BG-89894 combination has been discontinued.
Phase 1a: Objective Response Rate (ORR)
ORR is defined as the percentage of participants with confirmed CR or PR, as assessed by the investigator.
Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-58067
Phase 1a and 1b: Minimum observed plasma concentration (Cmin) of BGB-58067
Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-58067
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