Solid Tumor, Adult
Conditions
Keywords
Solid tumors, Advanced Solid Tumors, Metastatic Solid Tumors
Brief summary
This study aims to understand how safe and well-tolerated a drug called BGB-24714 is when used alone, or in combination with chemotherapy or radiation therapy, for people with advanced or spreading solid tumors. The main objective is to identify the highest tolerable dose or the highest administered dose of BGB-24714. Additionally, the study aims to identify the most suitable doses for further investigation in larger groups of participants.
Interventions
DRUGBGB-24714
administered orally
DRUGPaclitaxel
administered intravenously
DRUGCarboplatin
administered intravenously
DRUGDocetaxel
administered intravenously
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Eligibility Criteria : 1. Participants must sign a written informed consent form (ICF); and agree to comply with study requirement 2. Phase 1a (Dose Escalation): Part A, A-CN, and B: Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumor previously treated with standard systemic therapy or for whom treatment is not available or not tolerated Note: Only Chinese participants will be eligible for Part A-CN. Part C: Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III Non-small cell lung cancer (NSCLC) suitable for definitive chemoradiotherapy (CRT) Part D: Participant with locally advanced, histologically confirmed inoperable esophageal squamous cell carcinoma (ESCC) suitable for definitive CRT Phase 1b (Dose Expansion): Participants with histologically or cytologically confirmed solid tumors of selected types previously treated with standard therapy. 3. Participants must be able to provide formalin-fixed paraffin embedded (FFPE) tumor tissue sample. 4. Phase 1a Part A, A-CN, B and Phase 1b: ≥ 1 measurable lesion per Response evaluation criteria in solid tumors (RECIST) v1.1 5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 Key
Exclusion criteria
1. Active leptomeningeal disease or uncontrolled, untreated brain metastasis. 2. Any malignancy ≤ 3 years before the 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 with curative intent 3. Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s). 4. Clinically significant infection requiring systemic therapy ≤ 14 days before the first dose of study drug(s). 5. Prior exposure to agents with second mitochondria-derived activator of caspases (SMAC) mimetics, or other Inhibitors of apoptosis proteins (IAPs) antagonists. NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: Number of participants with adverse events (AEs) | approximately 6 months | Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs ), and experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria. |
| Dose Escalation: Maximum tolerated dose (MTD) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT) | approximately 6 months | — |
| Dose Escalation: Recommended Doses for Expansion (RDFE) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT) | approximately 6 months | Recommended dose based upon the MTD or MAD, as well as the long-term tolerability, pharmacokinetics, efficacy, and any other relevant data as available |
| Dose Expansion: Objective response rate (ORR) | approximately 2 Years | ORR is defined as the percentage of participants with partial or complete response, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: Objective response rate (ORR) | approximately 2 Years | ORR is defined as the percentage of participants with partial or complete response, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
| Dose Expansion: Progression-free Survival (PFS) | approximately 2 Years | PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of disease progression as determined by the investigator using RECIST v1.1 or death, whichever occurs first |
| Dose Expansion: Number of participants with adverse events | approximately 2 Years | Number of participants with AEs and SAEs |
| Duration of Response (DOR) | approximately 2 Years | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
| Disease Control Rate (DCR) | approximately 2 Years | DCR is defined as the percentage of participants whose best overall response is complete response, partial response, or stable disease, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
| Clinical Benefit Rate (CBR) | approximately 2 Years | CBR is defined as the percentage of participants who have complete response, partial response, and stable disease, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
| Plasma Concentrations of BGB-24714 and its metabolite | approximately 2 Years | — |
| Maximum Observed Plasma Concentration (Cmax) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
| Time to Maximum Plasma Concentration (Tmax) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
| Terminal Half-life (t1/2) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
| Area Under the Plasma Concentration Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
| Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
| Apparent Clearance (CL/F) of BGB-24714 | Up to 48 hours postdose | — |
| Apparent Volume Of Distribution (Vz/F) of BGB-24714 | Up to 48 hours postdose | — |
| Concentration at steady state (Cmax,ss) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
| Time to Maximum Plasma Concentration at steady state (Tmax,ss) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
| Area Under the Plasma Concentration Time Curve from Time 0 to the Last Quantifiable Concentration at Steady State (AUClast,ss) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
| Rough Concentration At Steady State (Ctrough,ss) of BGB-24714 and its metabolite | Up to 48 hours postdose | — |
Countries
Australia, China, New Zealand, South Korea, United States
Outcome results
None listed