Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors
Condition: Advanced Cancer
Intervention: BGB-A317; BGB-A317
Intervention description: In the dose escalation part, the dose levels were escalated following a modified 3+3 dose escalation scheme. In the scheduled exploration part, participants were assigned to doses and dose schedules. In the fixed dose exploration part, participants were assigned to dose group(s) not to exceed the maximum tolerated dose. In the dose expansion part, participants were assigned to different groups based on their tumor type.; Participants were assigned to different groups based on their tumor types
Intervention MeSH terms: Tislelizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 451.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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

Eligibility criteria:

        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.