Clinical trial NCT06625593: A First-in-Human Study of BG-C137, an Anti-FGFR2b Antibody Drug Conjugate, in Participants With Advanced Solid Tumors
Official title: A Phase 1a/b, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-C137, an Antibody-Drug Conjugate Targeting FGFR2b, in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: BG-C137
Advanced Solid Tumor
First-in-human
FGFR2b
ADC
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-10-03
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed advanced or metastatic solid tumors.
2. Life expectancy of ≥ 3 months.
3. 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.
4. 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.
5. ≥ 1 measurable lesion per RECIST v1.1.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
7. Adequate organ function as determined per protocol.

Exclusion Criteria:

1. Prior exposure to topoisomerase I inhibitor (TOP1i)-based antibody-drug conjugate (ADC) therapies or FGFR2b-targeted ADC therapies.
2. 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.
3. Spinal cord compression, or active leptomeningeal disease or uncontrolled, untreated brain metastasis.
4. 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).
5. Toxicities due to prior therapy that have not recovered.
6. 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.
7. 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.

Primary outcomes:
measure: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 2 years
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C137
timeFrame: Up to approximately 2 years
measure: Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BG-C137
timeFrame: Up to approximately 2 years
measure: Phase 1b: The recommended Phase 2 dose (RP2D) of BG-C137
timeFrame: Up to approximately 2 years
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Phase 1a: ORR
timeFrame: Up to approximately 2 years
measure: Phase 1a and 1b: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Phase 1a and 1b: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 2 years
measure: Phase 1a: Plasma concentrations of BG-C137 analytes
timeFrame: 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)
measure: Phase 1b: Plasma concentrations of BGB-C137 analytes
timeFrame: 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)
measure: Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-C137 analytes
timeFrame: Twice in the first 3 months
measure: Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-C137 analytes
timeFrame: Twice in the first 3 months
measure: Phase 1a: Minimum Observed Plasma Concentration (Ctrough) Of BGB-C137 analytes
timeFrame: Twice in the first 3 months
measure: Phase 1a: Area Under the Plasma Concentration-time Curve (AUC) of BGB-C137 analytes
timeFrame: Twice in the first 3 months
measure: Phase 1a: Terminal Half-Life (t1/2) of BGB-C137 analytes
timeFrame: Twice in the first 3 months
measure: Phase 1a and 1b: Incidence of Antidrug Antibodies (ADAs) to BGB-C137
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center (Nccc)
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Centre South Brisbane
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Malvern East
country: Australia
facility: Cabrini Hospital Malvern
state: Victoria
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital Branch Hospital
state: Shanghai
city: BundangGu SeongnamSi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: