An Investigational Study of BGB-58067 in Participants With Advanced Solid Tumors
- Registration Number
- NCT06589596
- Lead Sponsor
- BeiGene
- Brief Summary
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 as monotherapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.
- Detailed Description
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 as monotherapy in participants with advanced solid tumors and with MTAP deficiency.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 92
- 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 advanced, metastatic, or unresectable solid tumors, who have previously received standard systemic therapy or for whom treatment is not available or not tolerated
- Adequate organ function
- Prior treatment with any 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
- High cardiovascular risk factors
- QTcF > 470 ms based on the screening triplicate 12-lead ECG records
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a: Dose Escalation and Safety Expansion BGB-58067 Sequential cohorts of increasing dose levels of BGB-58067 as monotherapy will be evaluated. Phase 1b: Dose Expansion and Optimization BGB-58067 Recommended Dose(s) for Expansion (RDFE\[s\]) of BGB-58067 as monotherapy will be evaluated for selected indications based on emerging data.
- Primary Outcome Measures
Name Time Method Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events 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 2 years) Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) Approximately 1.5 years 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.
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-58067 Approximately 2 years RDFE of BGB-58067 will be determined based upon the MTD or MAD.
Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-58067 Approximately 2 years RP2D established from Phase 1a for BGB-58067 for administration in selected tumor types.
Phase 1b: Objective Response Rate (ORR) Approximately 2 years ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR), as assessed by the investigator.
- Secondary Outcome Measures
Name Time Method Phase 1a: Objective Response Rate (ORR) Approximately 2 years ORR is defined as the percentage of participants with confirmed CR or PR, as assessed by the investigator.
Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-58067 Approximately 2 years Phase 1a: Minimum observed plasma concentration (Cmin) of BGB-58067 Approximately 2 years Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-58067 Approximately 2 years Phase 1a: Apparent oral clearance (CL/F) for BGB-58067 Approximately 2 years Phase 1a: Half life (t1/2) of BGB-58067 Approximately 2 years Phase 1a: Area under the concentration-time curve (AUC) of BGB-58067 Approximately 2 years Phase 1a: Apparent volume of distribution (Vz/F) for BGB-58067 Approximately 2 years Phase 1a: Accumulation ratio (AR) for BGB-58067 Approximately 2 years Phase 1a and 1b: plasma concentrations of BGB-58067 Approximately 2 years Phase 1a and 1b: Duration of Response (DOR) Approximately 2 years 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.
Phase 1a and 1b: Disease Control Rate (DCR) Approximately 2 years DCR is defined as the percentage of participants with best overall response of a CR, PR, and stable disease, as assessed by the investigator.
Phase 1b: Number of Participants with AEs and SAEs 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 2 years) Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.
Phase 1b: Progression-Free Survival (PFS) Approximately 2 years 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.
Trial Locations
- Locations (45)
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
Jiangxi Cancer Hospital
🇨🇳Nanchang, Jiangxi, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Shanghai East Hospital Branch Hospital
🇨🇳Shanghai, Shanghai, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Usc Norris Comprehensive Cancer Center (Nccc)
🇺🇸Los Angeles, California, United States
Adventhealth
🇺🇸Celebration, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Laura and Isaac Perlmutter Cancer Center At Nyu Langone Health
🇺🇸New York, New York, United States
Sidney Kimmel Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Next Dallas
🇺🇸Irving, Texas, United States
Next Virginia
🇺🇸Fairfax, Virginia, United States
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, Shanghai, China
Fudan University Shanghai Cancer Centerpudong
🇨🇳Shanghai, Shanghai, China
Rigshospitalet
🇩🇰Copenhagen, Denmark
Centre de Lutte Contre Le Cancer Institut Bergonie
🇫🇷Bordeaux, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Institut Curie Paris
🇫🇷Paris, France
Institut de Cancerologie de Louest
🇫🇷St Herblain, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Samsung Medical Center
🇰🇷GangnamGu, Seoul Teugbyeolsi, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷SeodaemunGu, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center
🇰🇷SongpaGu, Seoul Teugbyeolsi, Korea, Republic of
Hospital Universitario Vall Dhebron
🇪🇸Barcelona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Start Madrid Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Hm Madrid Sanchinarro
🇪🇸Madrid, Spain