Advanced Solid Tumor
Conditions
Keywords
BGB-C354, Tislelizumab, First-in-human, Advanced solid tumor, Anti-PD-1 Monoclonal Antibody, B7H3, antibody drug conjugate
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. Maximum treatment duration will be up to two years. * The study duration is estimated to be approximately 5 years.
Detailed description
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGBGB-C354
Administered by intravenous infusion
DRUGTislelizumab
Administered by intravenous infusion
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 3. Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose cancer is not amenable to therapy with curative intent: 4. ≥ 1 measurable lesion per RECIST v1.1. 5. Able to provide an archived tumor tissue sample. 6. Adequate organ function. 7. 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). 8. 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).
Exclusion criteria
1. Prior treatment with B7H3-targeted therapy. 2. 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). 3. Participants with spinal cord compressions, active leptomeningeal disease or uncontrolled, or untreated brain metastasis 4. 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). 5. History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest \< 92%, or requirement for supplemental oxygen at baseline 6. 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). 7. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Approximately 24 months | 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-limiting toxicity (DLT) criteria |
| Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-C354 | Approximately 1 month | 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 1a: Recommended Dose for Expansion (RDFE) of BGB-C354 | Approximately 24 months | 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 |
| Phase 1b: Overall Response Rate (ORR) | Approximately 24 months | 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 | Approximately 24 months | The RP2D of BGB-C354 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: ORR | Approximately 24 months | 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 24 months | 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 24 months | 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) | Approximately 24 months | 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 as determined from tumor assessments by the investigator using RECIST v1.1. |
| Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events | Approximately 24 months | 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 | Twice in the first 3 months | — |
| Minimum observed plasma concentration (Cmin) for BGB-C354 | Approximately 12 months | — |
| Time to maximum plasma concentration (Tmax) for BGB-C354 | Twice in the first 3 months | — |
| Half-life (t1/2) for BGB-C354 | Twice in the first 3 months | — |
| Area under the concentration-time curve (AUC) for BGB-C354 | Twice in the first 3 months | — |
| Apparent clearance (CL/F) for BGB-C354 | Approximately 12 months | — |
| Apparent volume of distribution (Vz/F) for BGB-C354 | Approximately 12 months | — |
| Accumulation ratio for BGB-C354 | Approximately 12 months | — |
| Number of participants with anti-drug antibodies (ADAs) to BGB-C354 | Approximately 12 months | — |
| Serum concentration of BGB-C354 | Approximately 12 months | — |
Countries
Australia, China, United States
Contacts
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed