BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors
- Conditions
- Advanced Solid Tumor
- Interventions
- Registration Number
- NCT04649385
- Lead Sponsor
- BeiGene
- Brief Summary
The primary objective of this study is to assess the safety and tolerability of BGB-15025 alone and in combination with tislelizumab; and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended Phase 2 doses (RP2D) of BGB-15025 alone and in combination with tislelizumab in participants with advanced solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 157
- Phase 1a (dose escalation): Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have previously received standard systemic therapy or for whom treatment is not available, not tolerated or refused, and who have not received prior therapy targeting HPK1
- Phase 1b (dose expansion): Participant with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors, including non-small cell lung cancer, esophageal cancer or gastric/Gastroesophageal junction cancer (other solid tumors may be included) who have progressed following systemic anticancer therapies or have no prior systemic treatment for advanced disease
- At least 1 measurable lesion as defined per RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Adequate organ function as indicated by the following laboratory values up to first dose of study treatment: Hemoglobin≥ 90 g/L, Absolute neutrophil count ≥ 1.5 x 109/L , Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for participants with Gilbert syndrome ), AST and ALT≤ 2.5 x ULN
Key
- Active leptomeningeal disease or uncontrolled and untreated brain metastasis.
- Active autoimmune diseases or history of autoimmune diseases that may relapse
- Any active malignancy ≤ 2 years before the first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent
- 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
- History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including but not limited to pulmonary fibrosis, acute lung diseases, etc.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a: Dose Escalation BGB-15025 Part A: Participants will receive once daily of BGB-15025 monotherapy in sequential cohorts of approximately 7 increasing doses Part B: Participants will receive once daily of BGB-15025 in sequential cohorts plus 200mg tislelizumab on day 1 of each 21-day cycle (combination therapy ) Phase 1b: Dose Expansion BGB-15025 Phase 1b dose expansion will begin based upon the recommended doses for expansion (RDFE) for BGB-15025 alone or in combination with tislelizumab, and with or without chemotherapy as determined from Phase 1a Phase 1b: Dose Expansion Tislelizumab Phase 1b dose expansion will begin based upon the recommended doses for expansion (RDFE) for BGB-15025 alone or in combination with tislelizumab, and with or without chemotherapy as determined from Phase 1a Phase 1a: Dose Escalation Tislelizumab Part A: Participants will receive once daily of BGB-15025 monotherapy in sequential cohorts of approximately 7 increasing doses Part B: Participants will receive once daily of BGB-15025 in sequential cohorts plus 200mg tislelizumab on day 1 of each 21-day cycle (combination therapy )
- Primary Outcome Measures
Name Time Method Phase 1b: Overall Response Rate (ORR) as assessed by the investigator Up to 2 years Phase 1a: Number of Participants Experiencing Adverse Events (AEs) Up to 4 Years The maximum tolerated dose (MTD) of BGB-15025 Up to 3 Years The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%
Recommended Doses for Expansion (RDFE) of BGB-15025 monotherapy Up to 3 years The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%
RDFE of BGB-15025 in combination with tislelizumab Up to 3 years The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%
Phase 1a: Number of participants with dose limiting toxicities (DLTs) Up to 3 Years Participants will be considered evaluable for DLTs if they 1) received ≥ 80% of each scheduled study treatment administration during the DLT assessment window and/or 2) experienced a DLT.
Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs) Up to 4 years
- Secondary Outcome Measures
Name Time Method Phase 1a: Minimum observed plasma concentration (Cmin) of BGB-15025 Predose up to 8 hours postdose Duration Of Response (DOR) as assessed by the investigator Up to 3 years Phase 1a: Area under the concentration-time curve (AUC) of BGB-15025 Predose up to 8 hours postdose Phase 1a: Time to maximum plasma concentration (Tmax) of BGB-15025 Predose up to 8 hours postdose Phase 1b: Number of Participants Experiencing Adverse Events (AEs) Up to 3 years Phase 1b: Plasma Concentrations of the metabolite Predose up to 8 hours postdose Phase 1a: Overall Response Rate (ORR) as assessed by the investigator Up to 3 years Disease Control Rate (DCR) as assessed by the investigator Up to 3 years Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-15025 Predose up to 8 hours postdose Phase 1a: Half-life of (t1/2) of BGB-15025 Predose up to 8 hours postdose Phase 1a: Apparent clearance (CL/F) of BGB-15025 Predose up to 8 hours postdose Phase 1a: Apparent volume of distribution (Vz/F) of BGB-15025 Predose up to 8 hours postdose Phase 1a: Accumulation Ratio for Cmax of BGB-15025 Predose up to 8 hours postdose Phase 1a: Accumulation Ratio for AUC of BGB-15025 Predose up to 8 hours postdose Phase 1a: Metabolite to parent ratio for BGB-15025 and its metabolite Predose up to 8 hours postdose Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs) Up to 3 years Phase 1b: Plasma Concentrations of BGB-15025 Predose up to 8 hours postdose Phase 1b: Number of participants with dose limiting toxicities (DLTs) Up to 1 year Participants will be considered evaluable for DLTs if they 1) received ≥ 80% of each scheduled study treatment administration during the DLT assessment window and/or 2) experienced a DLT.
Trial Locations
- Locations (21)
The Catholic University of Korea, Seoul St Marys Hospital
🇰🇷SeochoGu, Seoul Teugbyeolsi, Korea, Republic of
Icahn School of Medicine At Mount Sinai
🇺🇸New York, New York, United States
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Ut Health San Antonio Mays Cancer Center
🇺🇸San Antonio, Texas, United States
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Ashford Cancer Centre Research Northeast
🇦🇺Windsor Gardens, South Australia, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
One Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, Shanghai, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Seoul National University Bundang Hospital
🇰🇷BundangGu SeongnamSi, 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
Asan Medical Center
🇰🇷SongpaGu, Seoul Teugbyeolsi, Korea, Republic of
Auckland City Hospital
🇳🇿Auckland, New Zealand