A First-in-Human Study of BGB-C354 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors
- Registration Number
- NCT06422520
- Lead Sponsor
- BeiGene
- Brief Summary
This is a first-in-human, Phase 1a/1b study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-C354 alone and in combination with tislelizumab in participants with advanced solid tumors.
Study details include:
* The study will be conducted in 2 phases: Phase 1a (Monotherapy Dose Escalation and Safety Expansion) and Phase 1b (Dose Expansion).
* The visit frequency will be approximately every 21 days during study treatment.
* The study duration is estimated to be approximately 5 years.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 62
- 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 of 0 or 1.
- Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose cancer is not amenable to therapy with curative intent:
- ≥ 1 measurable lesion per RECIST v1.1.
- Able to provide an archived tumor tissue sample.
- Adequate 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 B7H3-targeted therapy.
- For Part B and Phase 1b: Prior treatment with antibody drug conjugates (ADCs) with topoisomerase I inhibitor payload (for Phase 1b, unless otherwise specified for specific cohorts).
- Participants with spinal cord compressions, active leptomeningeal disease or uncontrolled, or 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 at baseline
- Uncontrolled diabetes, or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium levels despite standard medical management ≤ 14 days before the first dose of study drug(s).
- 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) BGB-C354 BGB-C354 monotherapy doses at sequentially increasing levels. Phase 1a: Part B (Safety Expansion) BGB-C354 Participants will enroll at safe dose levels recommended by the Safety Monitoring Committee (SMC) for further evaluation. Phase 1b: Part D (Combination Therapy Expansion) Tislelizumab BGB-C354 and tislelizumab will be adminsitered at doses determined by the SMC. Phase 1b: Part C (Monotherapy Expansion) BGB-C354 BGB-C354 will be administered at the recommended dose for expansion (RDFE). Phase 1b: Part D (Combination Therapy Expansion) BGB-C354 BGB-C354 and tislelizumab will be adminsitered at doses determined by the SMC.
- 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 characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0\]), timing, seriousness, and relationship to study drug(s); physical examinations; electrocardiograms (ECGs); and laboratory assessments as needed; and adverse events meeting protocol-defined dose-limitingtoxicity (DLT) criteria
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-C354 Up to approximately 2 years Defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% or the highest dose administered, respectively
Phase 1b: Overall Response Rate (ORR) Up to approximately 2 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 Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
Phase 1b: Recommended Phase 2 dose (RP2D) of BGB-C354 alone and in combination with tislelizumab Up to approximately 2 years The RP2D of BGB-C354 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-C354 Up to approximately 2 years The potential RDFE(s) of BGB-C354 will be determined based on the MTD or MAD, taking into consideration the long-term tolerability, pharmacokinetics (PK), preliminary antitumor activity, and any other relevant data, as available
- Secondary Outcome Measures
Name Time Method Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events Up to approximately 2 years Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0\]), timing, seriousness, and relationship to study drug(s); physical examinations; electrocardiograms (ECGs); and laboratory assessments as needed; and adverse events meeting protocol-defined dose-limitingtoxicity (DLT) criteria
Maximum observed plasma concentration (Cmax) for BGB-C354 Up to approximately 2 years Minimum observed plasma concentration (Cmin) for BGB-C354 Up to approximately 2 years Time to maximum plasma concentration (Tmax) for BGB-C354 Up to approximately 2 years Half-life (t1/2) for BGB-C354 Up to approximately 2 years Area under the concentration-time curve (AUC) for BGB-C354 Up to approximately 2 years Apparent clearance (CL/F) for BGB-C354 Up to approximately 2 years Apparent volume of distribution (Vz/F) for BGB-C354 Up to approximately 2 years Accumulation ratio for BGB-C354 Up to approximately 2 years Number of participants with anti-drug antibodies (ADAs) to BGB-C354 Up to approximately 2 years Serum concentration of BGB-C354 Up to approximately 2 years Disease Control Rate (DCR) Up to approximately 2 years DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease as determined from tumor assessments by the investigator 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(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.determined from tumor assessments by the investigator using RECIST v1.1.
Phase 1a: ORR Up to approximately 2 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) 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 disease progression or death, whichever occurs first as assessed by the investigator.
Trial Locations
- Locations (15)
Liaoning Cancer Hospital and Institute
🇨🇳Shenyang, Liaoning, China
Florida Cancer Specialist Research Institute Lake Nona
🇺🇸Orlando, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Next Oncology
🇺🇸San Antonio, Texas, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
One Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Guangxi Medical University Cancer Hospital
🇨🇳Nanning, Guangxi, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China