A Study of BGB-A3055, Alone and in Combination With Tislelizumab in Participants With Selected Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This study aims to test the safety, tolerability, and preliminary anti-tumor activity of BGB-A3055, either alone or in combination with Tislelizumab in participants with advanced or metastatic solid tumors.

Detailed Description
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The primary objective of the study is to assess the safety and tolerability of BGB-A3055 alone or in combination with Tislelizumab during dose escalation and to determine the recommended dose for expansion. During dose expansion, the primary objective will be to assess preliminary anti-tumor activity and further characterize the safety of the recommended dose for expansion. . Around 318 participants will be enrolled in this study, and they will be assigned to different treatment groups. Both the participants and their doctors will be aware of which treatment group they are assigned to throughout the study. The treatments, BGB-A3055 alone or in combination with Tislelizumab, will be administered intravenously to evaluate their safety and determine the highest dose that can be tolerated by participants. The study will be conducted at multiple medical centers worldwide. The expected duration of participation in this study is two years. Treatment will continue until participants no longer receive any benefits from the drugs, experience excessive side effects, or decide to withdraw their consent.

Official Title
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A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-A3055, Alone and in Combination With Tislelizumab in Patients With Selected Advanced or Metastatic Solid Tumors

Conditions
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Advanced Solid Tumor, Metastatic Solid Tumor, Solid Tumor

Intervention / Treatment
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* Drug: BGB-A3055
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 years on the day of signing the informed consent form (ICF) (or the legal age of consent in the jurisdiction in which the study is taking place, whichever is older). All participants are also required to demonstrate an ECOG Performance Status score of≤1 and have adequate organ function. Participants with histologically confirmed advanced or metastatic solid tumors associated with high CCR8 and who have previously received available standard systemic therapy or for whom treatment is not available or not tolerated and could not receive any prior therapy targeting CCR8. >=1 Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Participants should be able to provide the archival formalin-fixed paraffin-embedded (FFPE) tumor tissues (as block or unstained slides) or fresh biopsy if there is no archival tissue at baseline. For selected cohorts, participants should be willing to provide post-treatment fresh biopsy at specified timepoints. 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 (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast). Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) at screening. Participants with active hepatitis C, and participants with HIV infection. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B can be enrolled. Participants with a negative HCV antibody test result at screening or a positive HCV antibody test result followed by a negative HCV RNA test result at screening are eligible to participate. Participants with treated HIV infection may be included if certain criteria are met. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases . 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1a Part A: Dose Escalation (BGB-A3055 Monotherapy)<br>Different groups of participants will receive increasing doses of BGB-A3055 alone to determine the most appropriate dosage levels. | Drug: BGB-A3055<br>* Administered intravenously<br>|
| Experimental: Phase 1a Part B: Dose Escalation (BGB-A3055 + tislelizumab)<br>Different groups of participants will receive increasing doses of BGB-A3055 in combination with tislelizumab to determine the most appropriate dosage levels. | Drug: BGB-A3055<br>* Administered intravenously<br>Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;|
| Experimental: Phase 1b (Dose Expansion):<br>Participants will receive the recommended dose for expansion phase (RDFE) of BGB-A3055 in combination with tislelizumab to provide additional information on the safety, tolerability, and potential benefits of the recommended dose. | Drug: BGB-A3055<br>* Administered intravenously<br>Drug: Tislelizumab<br>* Administered intravenously<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 with adverse events (AEs) | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, and NCI-CTCAE v5.0. | Up to 2 Years | 
| Phase 1a: Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BGB-A3055 | The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% | Up to 2 Years | 
| Phase 1a: Recommended dose for expansion (RDFE) of BGB-A3055 | The RDFEs of BGB-A3055, alone and in combination with tislelizumab will be determined based on relevant data. | Up to 2 Years | 
| Phase 1b (Dose Expansion): Objective Response Rate (ORR) | Defined as the proportion of participants with best overall response (BOR) of a complete response (CR) or partial response (PR) as determined from tumor assessments by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a (Dose Escalation): Objective Response Rate (ORR) | ORR is defined as the percentage of participants with partial or complete response, as determined from tumor assessments by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to 2 Years | 
| Time to Response (TTR) | Defined as the time from the date of the first administration of study drug(s) to the first determination of an objective response.as determined from tumor assessments by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to 2 Years | 
| Duration of Response (DoR) | Defined as the time from the first determination of an objective response until the first documentation of disease progression or death due to any cause, whichever occurs first, as determined from tumor assessments by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to 2 Years | 
| Disease Control Rate (DCR) | Defined as the proportion of patients with BOR of a CR, PR, or stable disease as determined from tumor assessments by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to 2 Years | 
| Clinical Benefit Rate (CBR) | Defined as the proportion of patients with BOR of a CR, PR, or stable disease lasting ≥ 24 weeks as determined from tumor assessments by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to 2 Years | 
| Number of participants with anti-drug antibodies (ADAs) against BGB-A3055 |  | Up to 2 Years | 
| Number of participants with anti-drug antibodies (ADAs) against tislelizumab |  | Up to 2 Years | 
| Serum concentration of BGB-A3055 at specified time points |  | Up to 2 Years | 
| Phase 1b (Dose Expansion): Progression-Free Survival (PFS) | defined as the time from the date of the first administration of study drug(s) to the date of the first documentation of disease progression or death due to any cause, whichever occurs first, as determined from tumor assessments by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to 2 Years | 
| Phase 1b (Dose Expansion): Number of participants with adverse events (AEs) | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, physical examination findings, and electrocardiogram results. | Up to 2 Years | 
| Phase 1b (Dose Expansion) CCR8 expression | Evaluated from participant-derived tumor tissue(s) obtained before and/or after treatment with BGB-A3055 in combination with tislelizumab, and their association with clinical efficacy. | Up to 2 Years | 
| Phase 1b (Dose Expansion) PD-L1 expression | Evaluated from participant-derived tumor tissue(s) obtained before and/or after treatment with BGB-A3055 in combination with tislelizumab, and their association with clinical efficacy. | Up to 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BGB-A3055, Tislelizumab, Advanced solid tumors, Safety monitoring, Monoclonal antibody, Preliminary antitumor activity, Metastatic cancer, Metastatic Solid Tumor