Phase 1a/1b Study of BG-C9074, an Antibody Drug Conjugate Targeting B7H4, as Monotherapy and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors
Summary
This is a first-in-human, dose finding and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C9074 alone and in combination with other anticancer therapies in patients with advanced solid tumors.
Arms & interventions
- DrugBG-C9074
administered by intravenous infusion
- DrugTislelizumab
administered by intravenous infusion
- DrugBevacizumab
administered by intravenous infusion
Outcome measures
Primary
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with AEs and SAEs (as graded by the National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] Version \[v\] 5.0),, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity criteria.
Time frame: Approximately 3 years
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C9074
Defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 28% or the highest dose administered, respectively
Time frame: Approximately 18 months
Phase 1a: Recommended Dose for Expansion (RDFE) of BG-C9074.
The potential RDFE(s) of BG-C9074 alone and in combination with tislelizumab will be determined based on the MTD or MAD, taking into consideration the long-term tolerability, PK, pharmacodynamics, preliminary antitumor activity, and any other relevant data, as available
Time frame: Approximately 18 months
Phase 1b: Overall Response Rate (ORR) as monotherapy and in combination with tislelizumab
ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) assessed by the investigator using RECIST v1.1.
Time frame: Approximately 3 years
Phase 1b: Recommended Phase 2 dose (RP2D) of BG-C9074 as monotherapy and in combination with bevacizumab or tislelizumab
The RP2D of BG-C9074 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.
Time frame: Approximately 30 months
Secondary
Phase 1a: ORR as monotherapy and in combination with tislelizumab
Time frame: Approximately 3 years
Phase 1b: ORR as monotherapy and in combination with bevacizumab or tislelizumab
Time frame: Approximately 3 years
Phase 1b: ORR per B7-H4 (B7 homolog 4) protein expression
Time frame: Approximately 3 years
Duration of Response (DOR)
Time frame: Approximately 3 years
Duration of Response (DOR) per B7-H4 protein expression
Time frame: Approximately 3 years
Disease Control Rate (DCR)
Time frame: Approximately 3 years
Disease Control Rate (DCR) per B7-H4 protein expression
Time frame: Approximately 3 years
Clinical Benefit Rate (CBR)
Time frame: Approximately 3 years
Clinical Benefit Rate (CBR) per B7-H4 protein expression
Time frame: Approximately 3 years
Phase 1b: Progression Free Survival (PFS)
Time frame: Approximately 3 years
Phase 1b: Number of Participants with AEs and SAEs
Time frame: Approximately 3 years
Maximum observed plasma concentration (Cmax) for BG-C9074
Time frame: Twice in the first four months
Minimum observed plasma concentration (Cmin) for BG-C9074
Time frame: Approximately 3 years
Time to reach maximum observed plasma concentration (Tmax) for BG-C9074
Time frame: Twice in the first four months
Half-life (t1/2) for BG-C9074
Time frame: Twice in the first four months
Area under the concentration-time curve (AUC) for BG-C9074
Time frame: Twice in the first four months
Apparent clearance (CL/F) for BG-C9074
Time frame: Twice in the first four months
Apparent volume of distribution (Vz/F) for BG-C9074
Time frame: Twice in the first four months
Accumulation ratio for BG-C9074
Time frame: Twice in the first four months
Plasma concentrations for BG-C9074
Time frame: Approximately 3 years
Phase 1a: Number of participants with anti-drug antibodies (ADAs) to BG-C9074 and tislelizumab
Time frame: Approximately 3 years
Phase 1b: Number of participants with anti-drug antibodies (ADAs) to BG-C9074
Time frame: Approximately 3 years
Serum concentration of BG-C0974
Time frame: Approximately 3 years
Serum concentration of Tislelizumab
Time frame: Approximately 3 years
Eligibility criteria
Study locations (5)
Usc Norris Comprehensive Cancer Center (Nccc)
Los Angeles, California, 90089-1019
University of Colorado Cancer Center
Aurora, Colorado, 80045-2517
Florida Cancer Specialist Research Institute Lake Nona
Orlando, Florida, 32827-7400
Sidney Kimmel Comprehensive Cancer At Johns Hopkins
Baltimore, Maryland, 21287
James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210-1240