Safety and Preliminary Effectiveness of BGB-A445 in Combination With Tislelizumab in Participants With Advanced Solid Tumors

Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of the Anti OX40 Agonist Monoclonal Antibody BGB-A445 in Combination With the Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

The purpose of this study is to assess the safety and tolerability of BGB-A445 alone and in combination with tislelizumab in participants with advanced solid tumors; and to determine the maximum tolerated dose(s) (MTD) or maximum administered dose(s) (MAD) and recommended Phase 2 doses (RP2D) of BGB-A445 alone and in combination with tislelizumab.

Key Inclusion Criteria:

1. Phase 1a (dose escalation): Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for whom treatment is not available, not tolerated or refused.

1. Enrollment will be limited to participants with advanced solid tumors for which there is clinical evidence of response to T cell based immuno-oncology agents (eg, anti PD 1) or other scientific evidence in support of an immunologically sensitive tumor type.

2. Participant has not received prior therapy targeting OX40 or any other T cell agonist therapy (prior checkpoint inhibitor therapy is allowed)

   2. Phase 1b, the dose expansion phase, aims to include participants in specific tumor type cohorts who do not have access to standard systemic treatment, cannot tolerate it, or it is deemed inappropriate by the investigator. Cohort 1 focuses on non-small cell lung cancer (NSCLC) patients with advanced or metastatic disease, while Cohort 2 involves individuals with recurrent or metastatic head and neck squamous cell cancer (HNSCC). Cohort 3 includes participants with nasopharyngeal carcinoma (NPC), and Cohort 4 is for NSCLC patients with PD-L1 expression of at least 50%. Each cohort has specific eligibility criteria related to prior therapies, tumor characteristics, and treatment-free intervals.

   3. Has at least 1 measurable lesion as defined per RECIST 1.1. The target lesion(s) selected have not been previously treated with local therapy OR the target lesion(s) selected that are within the field of prior local therapy have subsequently progressed as defined by RECIST 1.1 4. Participants should be able to provide tumor tissue sample 5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 and a life expectancy of ≥ 6 months.

   6. Adequate organ function as indicated by the following laboratory values up to first dose of study drug

a. Participants must not have required blood transfusion or growth factor support ≤ 14 days before sample collection for the following:

• Absolute neutrophil count ≥ 1.5 x 10^9/L

• Platelet count ≥ 75 x 10^9/L

• Hemoglobin ≥ 90 g/L

  b. Estimated glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2 determined by the Cockcroft-Gault formula without correction for body surface area (BSA)

• The estimated GFR for participants with renal cell carcinoma must be ≥ 30 mL/min/1.73 m^2 by the Cockcroft-Gault formula

  c. Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for participants with Gilbert syndrome) d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN;

• ≤ 5 x ULN for participants with hepatocellular carcinoma or liver metastases

Key Exclusion Criteria:

1. Active leptomeningeal disease or uncontrolled brain metastasis. Participants with equivocal findings or with confirmed brain metastases are eligible for enrollment provided they are asymptomatic and radiologically stable without the need for corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s)

2. Active autoimmune diseases or history of autoimmune diseases that may relapse or history of life-threatening toxicity related to prior immune therapy, with the following exceptions:

   1. Controlled type 1 diabetes
   2. Hypothyroidism (provided it is managed with hormone-replacement therapy only)
   3. Controlled celiac disease
   4. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia)
   5. Any other disease that is not expected to recur in the absence of external triggering factors (requires consultation with the medical monitor prior to enrollment)

3. 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 (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)

4. 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:

   1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
   2. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
   3. 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)

5. Any major surgical procedure occurring ≤ 28 days before the first dose of study drug(s). If surgical procedure occurs > 28 days, they must have recovered adequately from the toxicity

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.