A Study of BG-C477 in Participants With Advanced Solid Tumors
- Registration Number
- NCT06596473
- Lead Sponsor
- BeiGene
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BG-C477 alone and in combination with anticancer agents in participants with selected advanced solid tumors.
- Detailed Description
This new study will check how safe and helpful a potential anticancer drug called BG-C477 is. This drug will be tested by itself or combined with other anticancer agents. The purpose of this study is to test if BG-C477 is safe and if it works in people with your disease when it is given on its own and in combination with other anticancer agents.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 21
- Participants must sign the informed consent form (ICF) and be capable of giving written informed consent
- Participants must consent to provide an archival tumor tissue sample or a fresh baseline biopsy
- Phase 1a (Dose Escalation); Histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, who were previously treated with at least 2 lines of standard systemic therapy or for whom no standard treatment is available in the medical judgment of the investigator
- ≥ 1 measurable lesion as assessed by RECIST v1.1
- Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
- Adequate organ function
- Female participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for ≥ 8 months after the last dose of BG-C477 and for ≥ 6 months after the last dose of chemotherapy, whichever comes later
- Nonsterile male participants must be willing to use a highly effective method of birth control and refrain from sperm donation for the duration of the study and for ≥ 5 months after the last dose of BG-C477, and for ≥ 3 months after chemotherapy, whichever comes later.
- Prior treatment with any carcinoembryonic antigen (CEA)-targeted ADCs or ADCs containing topoisomerase 1 (TOP1) inhibitor as payload
- History of severe allergic reactions, severe reaction to infusion, or hypersensitivity to the active ingredient and excipients of the study drug(s) or protein-based therapeutics
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- Any malignancy ≤ 2 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a: BG-C477 Monotherapy Dose Escalation BG-C477 Sequential cohorts of increasing dose levels of BG-C477 will be evaluated as monotherapy. Phase 1b Part A: BG-C477 Monotherapy Dose Optimization BG-C477 Participants with selected advanced solid tumors will be evaluated at different dose levels of RDFEs identified in Phase 1a. Phase 1b Part B: Combination Therapy Expansion Chemotherapy Sequential cohorts of increasing dose levels of BG-C477 will be evaluated in combination with chemotherapy. Phase 1a: BG-C477 Monotherapy Safety Expansion BG-C477 Selected dose levels that have been determined to be safe in Phase 1a dose escalation will be further evaluated in monotherapy. Phase 1b Part B: Combination Therapy Expansion BG-C477 Sequential cohorts of increasing dose levels of BG-C477 will be evaluated in combination with chemotherapy.
- Primary Outcome Measures
Name Time Method Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) From first dose of the study drug(s) to 30 days after the last dose (up to approximately 2 years) Number of participants with AEs and SAEs, including findings from abnormal laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria or protocol-defined Adverse Event of Special Interest (AESI) criteria.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) Approximately 1 year 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 BG-C477 Approximately 1 year RDFE of BG-C477 monotherapy will be determined based upon available data.
Phase 1b: Objective Response Rate (ORR) Approximately 2 years ORR is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Phase 1b: Recommended Phase 2 Dose (RP2D) of BG-C477 Approximately 2 years RP2D established from Phase 1a for BG-C477 for administration alone and in combination with chemotherapy.
- Secondary Outcome Measures
Name Time Method Phase 1a: ORR Approximately 1 year ORR is defined as the percentage of participants with best overall response of CR or PR, as assessed by the investigator per RECIST v1.1.
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 disease progression or death due to any cause, whichever occurs first, as assessed by the investigator per RECIST Version 1.1.
Phase 1a and 1b: Disease Control Rate (DCR) Approximately 2 years DCR is defined as the percentage of participants who achieve best overall response of CR, PR, or stable disease, as assessed by the investigator per RECIST Version 1.1.
Phase 1b: Progression-Free Survival (PFS) Approximately 2 years PFS is defined as the time from the first administration of study drug(s) to the date of first documentation of disease progression or death due to any cause, whichever occurs first, as assessed by the investigator per RECIST Version 1.1.
Phase 1b: Number of Participants with AEs and SAEs From first dose of the study drug(s) to 30 days after the last dose (up to approximately 2 years) Number of participants with AEs and SAEs, including findings from physical examinations, laboratory assessments, and that meet protocol-defined DLT criteria or protocol-defined AESI criteria.
Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BG-C477 antibody-drug conjugate (ADC), BG-C477 total antibody, and free payload Approximately 2 years Phase 1a and 1b: Minimum concentration (Cmin) of BG-C477 Approximately 2 years Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BG-C477 Approximately 2 years Phase 1a and 1b: Area under the concentration-versus-time curve during dosing interval (AUCtau) of BG-C477 Approximately 2 years Phase 1a and 1b: Apparent terminal elimination half-life (t1/2) of BG-C477 Approximately 2 years Phase 1a and 1b: Systemic clearance (CL/F) of BG-C477 Approximately 2 years Phase 1a and 1b: Apparent volume of distribution at steady state (Vss) of BG-C477 Approximately 2 years Phase 1a and 1b: Number of Participants with Antidrug Antibodies (ADAs) against BG-C477 Approximately 2 years
Trial Locations
- Locations (13)
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Yale University, Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Sun Yat Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Cancer Research South Australia
🇦🇺Adelaide, South Australia, Australia
Chongqing University Cancer Hospital
🇨🇳Chongqing, Chongqing, China
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
The Sixth Affiliated Hospital, Sun Yat Sen University
🇨🇳Guangzhou, Guangdong, China
One Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Auckland City Hospital
🇳🇿Auckland, New Zealand