A Study to Investigate the Antitumor Activity, Safety, Tolerability, and Pharmacokinetics of BGB-A445 in Combination With Tislelizumab in Participants With Select Advanced Solid Tumors.

Study Overview
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Brief Summary
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The objective of this study is to assess the overall response rate, evaluate the antitumor activity, and characterize the safety and tolerability of BGB-A445 alone or in combination with tislelizumab in participants With Advanced or Metastatic Urothelial Carcinoma (UC), Renal Cell Carcinoma (RCC), or Melanoma

Official Title
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Phase 1b/2 Study Investigating the Antitumor Activity, Safety, Tolerability, and Pharmacokinetics of the Anti-OX40 Agonist Monoclonal Antibody BGB-A445 in Combination With the Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced or Metastatic Urothelial Carcinoma, Renal Cell Carcinoma, or Melanoma

Conditions
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Urothelial Carcinoma, Renal Cell Carcinoma, Melanoma

Intervention / Treatment
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* Drug: BGB-A445
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants described in the following cohorts, who have received at least 1 but no more than 3 lines of prior systemic therapy for histologically or cytologically confirmed advanced and/or metastatic UC, RCC or melanoma Participants must not have received prior therapy targeting OX40 or any other T-cell agonists Has at least 1 measurable lesion as defined per RECIST v1.1. Participants must be able to provide an archived formalin-fixed paraffin embedded (FFPE) tumor tissue sample ECOG PS ≤ 1 (Participants with UC could have an ECOG PS ≤ 2) and a life expectancy of≥ 3 months Adequate organ function as indicated by the laboratory values up to the first dose of study drug(s) Exclusion Criteria: Active leptomeningeal disease or uncontrolled brain metastasis Active autoimmune diseases or history of autoimmune diseases that may relapse or history of life-threatening toxicity related to prior immune therapy Any active malignancy ≤ 2 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 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 drug(s), with the following exceptions: Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a nonautoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen) With uncontrolled diabetes, or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management, or ≥ Grade 3 hypoalbuminemia occurring ≤ 14 days before the first dose of study drug(s) 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Previously Treated UC Cohort A<br>BGB-A445 Monotherapy | Drug: BGB-A445<br>* administered intravenously<br>|
| Experimental: Previously Treated UC Cohort B<br>BGB-A445 and Tislelizumab | Drug: BGB-A445<br>* administered intravenously<br>Drug: Tislelizumab<br>* administered intravenously<br>|
| Experimental: Previously Treated RCC Cohort C<br>BGB-A445 Monotherapy | Drug: BGB-A445<br>* administered intravenously<br>|
| Experimental: Previously Treated RCC Cohort D<br>BGB-A445 and Tislelizumab | Drug: BGB-A445<br>* administered intravenously<br>Drug: Tislelizumab<br>* administered intravenously<br>|
| Experimental: Previously Treated Melanoma Cohort E<br>BGB-A445 Monotherapy | Drug: BGB-A445<br>* administered intravenously<br>|
| Experimental: Previously Treated Melanoma Cohort F<br>BGB-A445 and Tislelizumab | Drug: BGB-A445<br>* administered intravenously<br>Drug: Tislelizumab<br>* administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) as Assessed by the Investigator | ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR) | Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Determined from investigator derived tumor assessments as per RECIST 1.1 | Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first | 
| Duration of Response (DOR) | Determined from investigator derived tumor assessments as per RECIST 1.1 | Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first | 
| Disease-Control Rate (DCR) | Determined from investigator derived tumor assessments as per RECIST 1.1 | Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first | 
| Clinical benefit rate (CBR) | Determined from investigator derived tumor assessments as per RECIST 1.1 | Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first | 
| Number of Participants Experiencing Adverse Events (AEs) | As determined per National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), physical examinations, electrocardiograms (ECGs), and laboratory assessments as needed | Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy | 
| Number of Participants Experiencing Serious Adverse Events (SAEs) | As determined per National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), physical examinations, electrocardiograms (ECGs), and laboratory assessments as needed | Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy | 
| Serum Concentration of BGB-A445 |  | 60 minutes predose up to 72 hours postdose | 
| Serum Concentration of tislelizumab |  | 60 minutes predose up to 72 hours postdose | 
| Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies |  | Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Urothelial Carcinoma, Renal Cell Carcinoma, advanced solid tumors