Safety, Pharmacokinetics, and Antitumor Activity of BGB-B167 Alone and in Combination With Tislelizumab (BGB-A317) in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of BGB-B167 monotherapy and in combination with tislelizumab (BGB-A317) in participants with select advanced solid tumors.

Official Title
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A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B167, Alone and in Combination With Tislelizumab in Patients With Selected Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: BGB-B167
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors previously treated with standard systemic therapy or for whom treatment is not available, not tolerated, or refused, or not expected to provide significant clinical benefit or be tolerated in the medical judgement of the investigator Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 Adequate organ function as indicated by laboratory values during screening or ≤ 7 days before the first dose of study drug(s) Exclusion Criteria: Active leptomeningeal disease or uncontrolled, untreated brain metastasis Active autoimmune diseases or history of autoimmune diseases that may relapse 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 History of severe hypersensitivity reactions to other monoclonal antibody products or their excipients Women who are pregnant or are breastfeeding NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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: Increasing dose levels of BGB-B167 monotherapy; Part B: Increasing dose levels of BGB-B167 in combination with tislelizumab (BGB-A317) | Drug: BGB-B167<br>* Intravenous administration<br>Drug: Tislelizumab<br>* Intravenous administration<br>* Other names: BGB-A317;|
| Experimental: Phase 1b: Dose Expansion<br>BGB-B167 alone or in combination with tislelizumab (BGB-A317) | Drug: BGB-B167<br>* Intravenous administration<br>Drug: Tislelizumab<br>* Intravenous administration<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a: Number of Participants Experiencing Adverse Events (AEs) |  | Up to approximately 3 years | 
| Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs) |  | Up to approximately 3 years | 
| Phase 1a: Number of Participants Experiencing AEs Meeting Protocol-defined Dose-limiting Toxicity (DLT) Criteria |  | Up to approximately 3 years | 
| Phase 1a: Maximum tolerated dose (MTD) | MTD is defined as the highest tolerated dose with the target toxicity rate of 30% | Up to approximately 3 years | 
| Phase 1a: Recommended Phase 2 doses (RP2Ds) | RP2Ds of BGB-B167 alone or in combination with tislelizumab will be determined based on a biologically effective dose | Up to 90 days after the last dose of study drug(s); up to approximately 3 years | 
| Phase 1b: Objective Response Rate (ORR) | ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as determined by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a: ORR | ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as determined by investigators per RECIST v1.1 | Up to approximately 3 years | 
| Phase 1a and 1b: Duration of Response (DOR) | DOR is defined as the time from the first determination of a confirmed objective response until the first documentation of progression or death due to any cause, whichever occurs first, as determined by investigators per RECIST v1.1 | Up to approximately 3 years | 
| Phase 1a and 1b: Disease Control Rate (DCR) | DCR is defined as the percentage of participants with best overall response (BOR) of confirmed CR, PR, or stable disease, as determined by investigators per RECIST v1.1 | Up to approximately 3 years | 
| Phase 1a and 1b: Clinical Benefit Rate (CBR) | CBR is defined as the percentage of patients with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks, as determined by investigators per RECIST v1.1 | Up to approximately 3 years | 
| Phase 1b: Progression-free Survival (PFS) | PFS is defined as the time from the date of the first administration of study drug to the date of the first documentation of disease progression or death due to any cause, whichever occurs first, as determined by investigators per RECIST v1.1 | Up to approximately 3 years | 
| Phase 1a and 1b: Serum Concentration of Tislelizumab |  | Up to approximately 3 years | 
| Phase 1a and 1b: Maximum observed serum concentration (Cmax) of BGB-B167 |  | Up to approximately 3 years | 
| Phase 1a and 1b: Minimum observed serum concentration (Cmin) of BGB-B167 |  | Up to approximately 3 years | 
| Phase 1a and 1b: Time to reach maximum observed serum concentration (Tmax) of BGB-B167 |  | Up to approximately 3 years | 
| Phase 1a and 1b: Elimination half life (t1/2) of BGB-B167 |  | Up to approximately 3 years | 
| Phase 1a and 1b: Area under the concentration-time curve in 1 dosing interval (AUCtau) of BGB-B167 |  | Up to approximately 3 years | 
| Phase 1a and 1b: Total body clearance (CL) of BGB-B167 |  | Up to approximately 3 years | 
| Phase 1a and 1b: Volume of distribution at steady state (Vss) of BGB-B167 |  | Up to approximately 3 years | 
| Phase 1b: Number of Participants with AEs or SAEs |  | Up to approximately 3 years | 
| Phase 1a and 1b: Number of Participants with Antidrug Antibodies (ADAs) |  | Up to approximately 3 years |