A First-in-Human Study of BG-C137, an Anti-FGFR2b Antibody Drug Conjugate, in Participants With Advanced Solid Tumors
- Registration Number
- NCT06625593
- Lead Sponsor
- BeiGene
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C137 in participants with advanced solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 68
- Histologically or cytologically confirmed advanced or metastatic solid tumors.
- Life expectancy of ≥ 3 months.
- Prior standard systemic therapy in the advanced or metastatic setting. Dose Escalation: Participants for whom further standard treatment is not available, not tolerated or determined not appropriate based on the investigator's judgment. Safety Expansion and Dose Expansion: Participants who have received 1 or 2 prior lines of systemic therapy in the advanced or metastatic setting.
- Participants must provide agreement for collection of archival tissue or recently obtained fresh tumor biopsy for central evaluation of FGFR2b expression levels and other biomarker assessments.
- ≥ 1 measurable lesion per RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Adequate organ function as determined per protocol.
- Prior exposure to topoisomerase I inhibitor (TOP1i)-based antibody-drug conjugate (ADC) therapies or FGFR2b-targeted ADC therapies.
- Active or chronic corneal disorder, history of corneal transplantation, corneal keratitis, keratoconjuntivitis, keratopathy, corneal abrasion, inflammation or ulceration, other active ocular conditions and any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
- Spinal cord compression, or active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- Systemic antitumor therapy (including targeted therapy and immunotherapy ≤ 14 days, ≤ 28 days for immuno- oncological antibody, ≤ 14 days or 5 half-lives [whichever is shorter] for chemotherapy, ADCs, or investigational therapy) before first dose of study drug(s).
- Toxicities due to prior therapy that have not recovered.
- Any malignancy ≤ 2 years before 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.
- History of interstitial lung disease (ILD), noninfectious pneumonitis, oxygen saturation at rest < 92%, or requirement for supplemental oxygen at baseline.
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 BG-C137 Sequential cohorts of increasing dose levels of BG-C137 will be evaluated as monotherapy Phase 1b: Dose Expansion BG-C137 Recommended Dose(s) of BG-C137 as determined from Ph1a will be evaluated in select indications
- Primary Outcome Measures
Name Time Method Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to approximately 2 years Number of participants with AEs and SAEs as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version (NCI CTCAE 5.0)), including AEs that meet protocol-defined dose-limiting toxicity (DLT) criteria and AEs meeting protocol-defined adverse event of special interest (AESIs)
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C137 Up to approximately 2 years The MTD or MAD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to a target toxicity rate, or the highest dose administered, respectively.
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BG-C137 Up to approximately 2 years RDFE(s) is determined based on relevant data, as available
Phase 1b: The recommended Phase 2 dose (RP2D) of BG-C137 Up to approximately 2 years The RP2D of BG-C137 monotherapy will be determined based on relevant data, as available
Phase 1b: Overall Response Rate (ORR) Up to approximately 2 years ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) by Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
- Secondary Outcome Measures
Name Time Method Phase 1a: ORR Up to approximately 2 years ORR is defined as the percentage of participants with CR or PR, as determined by RECIST v1.1
Phase 1a and 1b: Disease Control Rate (DCR) Up to 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 RECIST v1.1
Phase 1a and 1b: Duration of Response (DOR) Up to approximately 2 years DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of progression or death, whichever comes first, as assessed using RECIST v1.1
Phase 1b: Progression Free Survival (PFS) Up to approximately 2 years PFS is defined as the time from the date of the first dose of study drug to the date of the first documentation of progressive disease assessed using RECIST v1.1 or death, whichever occurs first
Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to approximately 2 years Number of participants with AEs and SAEs as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version (NCI CTCAE 5.0), and AEs meeting protocol-defined adverse event of special interest (AESIs)
Phase 1a: Plasma concentrations of BG-C137 analytes Up to approximately 1 year; at the end of treatment (maximum of 2 years) and at the first safety follow-up visit (30 days after last dose) Phase 1b: Plasma concentrations of BGB-C137 analytes Up to approximately 1 year; at the end of treatment (maximum of 2 years) and at the first safety follow-up visit (30 days after last dose) Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-C137 analytes Twice in the first 3 months Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-C137 analytes Twice in the first 3 months Phase 1a: Minimum Observed Plasma Concentration (Ctrough) Of BGB-C137 analytes Twice in the first 3 months Phase 1a: Area Under the Plasma Concentration-time Curve (AUC) of BGB-C137 analytes Twice in the first 3 months Phase 1a: Terminal Half-Life (t1/2) of BGB-C137 analytes Twice in the first 3 months Phase 1a and 1b: Incidence of Antidrug Antibodies (ADAs) to BGB-C137 Up to approximately 2 years
Trial Locations
- Locations (20)
Samsung Medical Center
🇰🇷GangnamGu, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center
🇰🇷SongpaGu, Seoul Teugbyeolsi, Korea, Republic of
Usc Norris Comprehensive Cancer Center (Nccc)
🇺🇸Los Angeles, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Icon Cancer Centre South Brisbane
🇦🇺South Brisbane, Queensland, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Cabrini Hospital Malvern
🇦🇺Malvern East, Victoria, Australia
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Shanghai East Hospital Branch Hospital
🇨🇳Shanghai, Shanghai, China
Seoul National University Bundang Hospital
🇰🇷BundangGu SeongnamSi, Gyeonggi-do, 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