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

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring OX40, PD-1 Read More

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 (dose expansion): Participants in specific tumor type cohorts for whom standard systemic treatment is not available, not tolerated, or refused. Participant must not have received prior therapy targeting OX40 or any other T-cell agonist. Prior checkpoint inhibitor therapy is allowed. Note: Refused treatment not applicable in South Korea.

   1. Cohort 1 (NSCLC): Patients with histologically or cytologically confirmed stage IIIB, IIIC, or IV disease whose tumor is not amenable to local therapy with curative intent (ie. surgery or radiotherapy with or without chemotherapy), who have received ≥1 but no more than 3 lines of prior systemic therapy for advanced or metastatic disease. Patients who progressed within 6 months following completion of systemic therapy for local disease should have received a platinum-based agent. Patients who are eligible to receive targeted therapy (if actionable oncogenic driver mutations with locally approved therapy were identified [eg. EGFR, ALK or other]) must have received appropriate targeted therapy.
   2. Cohort 2 (HNSCC): Patients with histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell cancer whose tumor is not amenable to local therapy with curative intent (ie. surgery or radiotherapy with or without chemotherapy), and who have received ≥1 but no more than 3 lines of prior systemic therapy for recurrent or metastatic disease or progressed within 6 months following completion of systemic therapy for local disease.
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 must be able to provide an archived formalin fixed paraffin embedded (FFPE) tumor tissue sample (block or approximately 15 freshly unstained FFPE slides) after the most recent line of therapy. If archival tissue is not available, fresh tumor biopsy is mandatory.

   a. Participants enrolled must provide baseline tumor tissue as outlined as well as be willing and medically fit to undergo mandatory on treatment biopsies with no excessive risk as judged by the investigator

5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1

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

   1. 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 ≥ 90g/L

   2. 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
   3. Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for participants with Gilbert syndrome)

   4. 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 and/or complications from the intervention before the first dose of study drug(s).

6. Any of the following cardiovascular risk factors:

   1. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before the first dose of study drug(s)
   2. Pulmonary embolism ≤ 28 days before the first dose of study drug(s)
   3. Any history of acute myocardial infarction ≤ 6 months before the first dose of study drug(s)
   4. Heart failure that meets the New York Heart Association Classification III or IV ≤ 6 months before the first dos6.e of study drug(s)
   5. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before the first dose of study drug(s)
   6. Any history of cerebrovascular accident ≤ 6 months before the first dose of study drug(s)
   7. Uncontrolled hypertension: systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg on repeated measurements that cannot be managed by standard antihypertension medications ≤ 28 days before the first dose of study drug(s)
   8. Any episode of syncope or seizure ≤ 28 days before the first dose of study drug(s)

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