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, and in combination with standard of care therapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.
BGB-58067 is a new drug designed to target a specific protein called protein arginine methyltransferase 5 (PRMT5). This protein is involved in many cell activities and can promote cancer growth when it is overactive. High levels of PRMT5 are linked to poor outcomes in several types of cancer. This new study will check how safe and helpful a potential anticancer drug called BGB-58067 is. This drug will be tested alone, in combination with BG-89894, and in combination with standard of care therapy in participants with advanced solid tumors and with MTAP deficiency. Note: Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
244
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.
Time frame: From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 13 months)
Phase 1a: Number of Participants with Adverse Events that meet Dose-Limiting Toxicity (DLT) criteria
Time frame: Approximately 1 month
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.
Time frame: Approximately 1 month
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.
Time frame: Approximately 13 months
Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy
RP2D established from Phase 1a for BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy for administration in selected tumor types.
Time frame: Approximately 2 years
Phase 1b: Objective Response Rate (ORR)
ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR), as assessed by the investigator.
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Usc Norris Comprehensive Cancer Center (Nccc)
Los Angeles, California, United States
RECRUITINGAdventhealth
Celebration, Florida, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGWashington University School of Medicine
St Louis, Missouri, United States
RECRUITINGNyu Langone Health
New York, New York, United States
RECRUITINGSidney Kimmel Cancer Center
Philadelphia, Pennsylvania, United States
RECRUITINGThe University of Texas Md Anderson Cancer Center
Houston, Texas, United States
RECRUITINGNext Dallas
Irving, Texas, United States
RECRUITINGNext Virginia
Fairfax, Virginia, United States
RECRUITINGBlacktown Cancer and Haematology Centre
Blacktown, New South Wales, Australia
RECRUITING...and 37 more locations
Time frame: Approximately 2 years
Phase 1a: Objective Response Rate (ORR)
ORR is defined as the percentage of participants with confirmed CR or PR, as assessed by the investigator.
Time frame: Approximately 2 years
Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-58067
Time frame: Approximately 2 months
Phase 1a and 1b: Minimum observed plasma concentration (Cmin) of BGB-58067
Time frame: Approximately 9 months
Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-58067
Time frame: Approximately 2 months
Phase 1a and 1b: Apparent oral clearance (CL/F) for BGB-58067
Time frame: Approximately 2 months
Phase 1a and 1b: Half-life (t1/2) of BGB-58067
Time frame: Approximately 2 months
Phase 1a and 1b: Area under the concentration-time curve (AUC) of BGB-58067
Time frame: Approximately 2 months
Phase 1a and 1b: Apparent volume of distribution (Vz/F) for BGB-58067
Time frame: Approximately 2 months
Phase 1a and 1b: Accumulation ratio (AR) for BGB-58067
Time frame: Approximately 2 months
Phase 1a and 1b: Plasma concentrations of BGB-58067
Time frame: Approximately 9 months
Phase 1a and 1b: Duration of Response (DOR)
DOR is defined as the time from the first determination of an objective response until first documentation of progression or death, whichever occurs first, as assessed by the investigator.
Time frame: Approximately 2 years
Phase 1a and 1b: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with best overall response of a CR, PR, and stable disease, as assessed by the investigator.
Time frame: Approximately 2 years
Phase 1b: Number of Participants with AEs and SAEs
Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.
Time frame: From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 13 months)
Phase 1b: Progression-Free Survival (PFS)
PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of progressive disease assessed by investigator or death, whichever occurs first, as assessed by the investigator.
Time frame: Approximately 2 years