Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors

A Phase 1A/1B, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activities of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Subjects With Advanced Tumors

This study evaluated the safety, tolerability, pharmacokinetic profile and treatment effect of a new drug known as BGB-A317 in participants with advanced tumors.

Key Inclusion Criteria:

1. Participants must have had a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy was available.

   1. For Phase 1A: no specific restriction
   2. For Phase 1B: histology specified below:

   i. non-small cell lung cancer (participants with documented epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement should have been excluded) ii. ovarian cancer iii. gastric cancer iv. hepatocellular carcinoma (HCC, Barcelona-Clinic Liver Cancer stage C, stage B not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach, and Child-Pugh A) v. head and neck squamous cell carcinoma vi. esophageal carcinoma vii. triple negative breast cancer viii. cholangiocarcinoma ix. renal cell cancer, bladder cancer, melanoma, Merkel-cell carcinoma, sarcoma, gastrointestinal stromal tumor, or cutaneous squamous cell carcinoma. Or any other solid tumors with known microsatellite instability-high or mismatch repair deficient status, such as colorectal cancer or pancreatic cancer

2. Participants with previously treated brain metastasis (es) that were asymptomatic or radiographically/clinically stable and not requiring steroids medications for 4 weeks prior to enrollment were permitted.

3. Participants must have had archival tumor tissues or agreed to a tumor biopsy for analysis of predictive biomarkers such as programmed death-ligand 1 (PD-L1). (Fresh tumor biopsies were strongly recommended at baseline for biomarker analysis in participants with readily accessible tumor lesions and who consented to the biopsies).

4. Participants must have had measurable disease as defined per Response Evaluation Criteria in Solid Tumor Version 1.1.

5. Eastern Cooperative Oncology Group performance status of ≤ 1.

6. Participants must have had adequate organ function as indicated by the following laboratory values:

   • Absolute neutrophil count ≥ 1,500 /microliter
   • Platelets ≥ 100,000 / milliliter (mL)
   • Hemoglobin ≥ 9 grams/deciliter or ≥ 5.6 millimoles/liter
   • Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
   • Serum total bilirubin ≤ 1.5 X ULN
   • Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 X ULN or ≤ 5 X ULN for participants with liver metastases
   • International normalized ratio or prothrombin time ≤ 1.5 X ULN
   • Activated partial thromboplastin time ≤ 1.5 X ULN

Key Exclusion Criteria:

1. History of severe hypersensitivity reactions to other Monoclonal antibodies.

2. Prior malignancy active within the previous 2 years except for tumor for which a participant was enrolled in the study, and locally curable cancers that had been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.

3. Prior therapies targeting PD-1 or PD-L1.

4. Participants who failed to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers.

5. Participants with active autoimmune diseases or history of autoimmune diseases should have been excluded.

6. Participants should have been excluded if they had a condition requiring systemic treatment with either corticosteroids (> 10 milligrams daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.

7. Had history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.

8. Known history of human immunodeficiency virus.

9. Active infection requiring therapy, positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid except in participant with HCC, who met the following criteria:

   • Hepatitis B virus (HBV) viral load < 200 international units/mL (approximately 1000 combined positive score/mL)
   • Participants with active HBV infection needed to be on anti-HBV suppression ≥ 3 months, throughout treatment and for 6 months after
   • Participants hepatitis C virus (HCV)-positive after successful treatment (defined as sustained virologic response [SVR] 12 or SVR 24) were allowed as long as 4 weeks had passed between completion of HCV therapy and start of study drug

10. Use of any vaccines against infectious diseases (for example, influenza, varicella) within 4 weeks (28 days) of initiation of study therapy and 60 days after the last administration of the study medication.

Note: Other protocol defined Inclusion/Exclusion criteria may have applied.