BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors

Study Overview
=================
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.

Official Title
-----------------
A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of HPK1 Inhibitor BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

Conditions
-----------------
Advanced Solid Tumor

Intervention / Treatment
-----------------
* Drug: BGB-15025
* Drug: Tislelizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1a: Dose Escalation<br>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 ) | Drug: BGB-15025<br>* Administered orally once or twice daily (QD or BID)<br>Drug: Tislelizumab<br>* Administered 200 mg intravenous (IV) infusion<br>* Other names: BGB-A317;|
| Experimental: Phase 1b: Dose Expansion<br>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 | Drug: BGB-15025<br>* Administered orally once or twice daily (QD or BID)<br>Drug: Tislelizumab<br>* Administered 200 mg intravenous (IV) infusion<br>* Other names: BGB-A317;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a: Number of participants with dose limiting toxicities (DLTs) | 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. | Up to 3 Years | 
| Phase 1a: Number of Participants Experiencing Adverse Events (AEs) |  | Up to 4 Years | 
| Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs) |  | Up to 4 years | 
| The maximum tolerated dose (MTD) of BGB-15025 | The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% | Up to 3 Years | 
| Recommended Doses for Expansion (RDFE) of BGB-15025 monotherapy | The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% | Up to 3 years | 
| RDFE of BGB-15025 in combination with tislelizumab | The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% | Up to 3 years | 
| Phase 1b: Overall Response Rate (ORR) as assessed by the investigator |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a: Overall Response Rate (ORR) as assessed by the investigator |  | Up to 3 years | 
| Duration Of Response (DOR) 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: Minimum observed plasma concentration (Cmin) 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 1a: Half-life of (t1/2) of BGB-15025 |  | Predose up to 8 hours postdose | 
| Phase 1a: Area under the concentration-time curve (AUC) 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 Adverse Events (AEs) |  | Up to 3 years | 
| 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: Plasma Concentrations of the metabolite |  | Predose up to 8 hours postdose | 
| Phase 1b: Number of participants with dose limiting toxicities (DLTs) | 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. | Up to 1 year |