Advanced Solid Tumor, Solid Tumor
Conditions
Keywords
advanced solid tumor, BGB-26808, BGB-A317, Tislelizumab, PD1, HPK1
Brief summary
This is an open-label, multicenter, and nonrandomized dose escalation and dose expansion study to evaluate BGB-26808 as monotherapy or in combination with tislelizumab in participants with advanced solid tumors. The main purpose of this study is to explore the recommended dosing for BGB-26808.
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-26808
Planned doses administered orally as a tablet daily.
DRUGTislelizumab
Planned doses administered by intravenous infusion.
DRUGChemotherapy
Administered in accordance with relevant local guidelines and/or prescribing information.
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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 ≤ 1. 3. Phase 1a: Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors that are immune-sensitive who have previously received standard systemic therapy, or for whom treatment is not available or not tolerated, or for whom treatment is determined not appropriate based on investigator's judgment and who have not received prior therapy targeting hematopoietic progenitor kinase 1 (HPK1). 4. Phase 1b: Participants with histologically confirmed locally advanced unresectable or metastatic tumor types and who have not had prior systemic treatment. Participants who received prior systemic therapy in a neo-adjuvant or adjuvant setting with curative intent for nonmetastatic disease must have experienced a disease-free interval of ≥ 6 months from the last dose of systemic therapy prior to the first dose of study treatments. 5. ≥ 1 measurable lesion per RECIST v1.1. 6. Able to provide an archived tumor tissue sample. 7. Adequate organ function. 8. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for ≥ 90 days after the last dose of BGB-26808, or for ≥ 120 days after the last dose of tislelizumab, or for up to ≥ 270 days after the last dose of chemotherapy. 9. Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study treatment period and for ≥ 90 days after the last dose of BGB-26808, or for ≥ 120 days after the last dose of tislelizumab, or for ≥ 180 days after the last dose of chemotherapy.
Exclusion criteria
1. Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, anti-CTLA4, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways. 2. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention. 3. Clinically significant bleeding from the gastrointestinal tract within 28 days before the first dose of study treatment(s). 4. Active leptomeningeal disease or uncontrolled, untreated brain metastasis. 5. Active autoimmune diseases or history of autoimmune diseases that may relapse 6. Any malignancy ≤ 3 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). 7. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study treatment(s). 8. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases. 9. Uncontrolled diabetes. 10. 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) | From the first dose of study drug(s) to 90 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 12 months | 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 BGB-26808 | Approximately 1 month | MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached. |
| Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-26808 | Approximately 1 month | RDFE of BGB-26808 alone or in combination with tislelizumab will be determined based upon the MTD or MAD. |
| Phase 1b: Overall Response Rate (ORR) | Approximately 6 months | ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: ORR | Approximately 6 months | ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) assessed by the investigator using RECIST v1.1. |
| Phase 1a and 1b: Duration of Response (DOR) | Approximately 9 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. |
| Phase 1a and 1b: Disease Control Rate (DCR) | Approximately 6 months | DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease. It will be summarized similarly as ORR as assessed by the investigator. |
| Phase 1a and 1b: Clinical Benefit Rate (CBR) | Approximately 6 months | 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 9 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. |
| Phase 1a and 1b: Plasma concentrations of BGB-26808 | Approximately 6 months | — |
| Phase 1a and 1b: Maximum observed plasma concentration (Cmax) for BGB-26808 | Approximately 1 month | — |
| Phase 1a and 1b: Time to maximum plasma concentration (Tmax) for BGB-26808 | Approximately 1 month | Pharmacokinetic analysis for BGB-26808 concentrations, alone or in combination with tislelizumab. Single-dose and steady-state PK parameters. |
| Phase 1a and 1b: Area under the concentration-time curve (AUC) for BGB-26808 | Approximately 1 month | — |
| Phase 1b: Number of Participants with AEs and SAEs | From the first dose of study drug(s) to 90 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 12 months | Number of participants with AEs and SAEs, including findings from physical examinations, ECGs, laboratory assessments, and that meet protocol-defined dose-limiting toxicity criteria. |
Countries
Australia, China, New Zealand, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed