Phase 1a/1b First-in-Human Study of BG-C9074 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors
- Registration Number
- NCT06233942
- Lead Sponsor
- BeiGene
- Brief 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 tislelizumab in participants with advanced solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 227
- Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
- Participants with selected histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have been previously treated.
- ≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
- Able to provide an archived tumor tissue sample.
- Adequate bone marrow and organ function.
- Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for ≥ 7 months after the last dose of study drug(s).
- Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study treatment period and for ≥ 4 months after the last dose of study drug(s).
- Prior treatment with a B7 homolog 4 (B7H4)-targeting antibody-drug conjugate (ADC) or an ADC with a topoisomerase 1 inhibitor (TOP1i) payload.
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- Any malignancy ≤ 2 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
- History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest < 92%, or requirement for supplemental oxygen (including intermittent use) at baseline.
- Uncontrolled diabetes.
- Infection (including tuberculosis infection) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study treatment(s).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1a: Part A (Monotherapy Dose Escalation) BG-C9074 BG-C9074 monotherapy dose escalation Phase 1a: Part B (Monotherapy Safety Expansion) BG-C9074 BG-C9074 dose levels that have been determined to be safe and tolerable in Part A will be investigated. Phase 1a: Part C (Combination Therapy Dose Escalation) BG-C9074 BG-C9074 plus tislelizumab combination at the recommended dose for expansion (RDFE). Phase 1a: Part C (Combination Therapy Dose Escalation) Tislelizumab BG-C9074 plus tislelizumab combination at the recommended dose for expansion (RDFE). Phase 1b: Monotherapy Dose Expansion BG-C9074 The monotherapy dose expansion phase will begin once the BG-C9074 monotherapy RDFE and dosing schedule have been determined from Parts A and B in Phase 1a. Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus tislelizumab) BG-C9074 Combination therapy will begin post-completion of combination dose escalation (Part C, Phase 1a). Phase 1b: Combination Therapy Dose Expansion (BG-C9074 plus tislelizumab) Tislelizumab Combination therapy will begin post-completion of combination dose escalation (Part C, Phase 1a).
- Primary Outcome Measures
Name Time Method Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Approximately 3 years Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity criteria.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C9074 Approximately 18 months 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
Phase 1a: Recommended Dose for Expansion (RDFE) of BG-C9074. Approximately 18 months 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
Phase 1b: Overall Response Rate (ORR) Approximately 3 years 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.
Phase 1b: Recommended Phase 2 dose (RP2D) of BG-C9074 as monotherapy and in combination with tislelizumab Approximately 30 months The RP2D of BG-C9074 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.
- Secondary Outcome Measures
Name Time Method Phase 1a: ORR Approximately 3 years 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.
Duration of Response (DOR) Approximately 3 years DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.
Disease Control Rate (DCR) Approximately 3 years DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease.
Clinical Benefit Rate (CBR) Approximately 3 years CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks as assessed by investigator.
Phase 1b: Progression Free Survival (PFS) Approximately 3 years PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.
Phase 1b: Number of Participants with AEs and SAEs Approximately 3 years Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity criteria.
Maximum observed plasma concentration (Cmax) for BG-C9074 Twice in the first four months Minimum observed plasma concentration (Cmin) for BG-C9074 Approximately 3 years Time to reach maximum observed plasma concentration (Tmax) for BG-C9074 Twice in the first four months Half-life (t1/2) for BG-C9074 Twice in the first four months Area under the concentration-time curve (AUC) for BG-C9074 Twice in the first four months Apparent clearance (CL/F) for BG-C9074 Twice in the first four months Apparent volume of distribution (Vz/F) for BG-C9074 Twice in the first four months Accumulation ratio for BG-C9074 Twice in the first four months Plasma concentrations for BG-C9074 Approximately 3 years Number of participants with anti-drug antibodies (ADAs) to BG-C9074 Approximately 3 years Serum concentration of BG-C0974 Approximately 3 years Serum concentration of Tislelizumab Approximately 3 years
Trial Locations
- Locations (36)
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Mengchao Hepatobiliary Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Cancer Hospital Chinese Academy of Medical Scienceslangfang Branch
🇨🇳Langfang, Hebei, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
The First Affiliated Hospital of Xian Jiaotong University
🇨🇳Xian, Shaanxi, China
Affiliated Hospital of Jining Medical University
🇨🇳Jining, Shandong, China
Obstetrics and Gynecology Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Usc Norris Comprehensive Cancer Center (Nccc)
🇺🇸Los Angeles, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Florida Cancer Specialist Research Institute Lake Nona
🇺🇸Orlando, Florida, United States
Sidney Kimmel Comprehensive Cancer At Johns Hopkins
🇺🇸Baltimore, Maryland, United States
James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Macquarie University
🇦🇺North Ryde, New South Wales, Australia
Cancer Care Wollongong
🇦🇺Wollongong, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Sun Yat Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Weifang Peoples Hospital
🇨🇳Weifang, Shandong, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Cha Bundang Medical Center, Cha University
🇰🇷BundangGu SeongnamSi, Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷BundangGu SeongnamSi, Gyeonggi-do, Korea, Republic of
National Cancer Center (Korea)
🇰🇷IlsandongGu GoyangSi, Gyeonggi-do, Korea, Republic of
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