Clinical Trials

Inclusion Criteria - Phase 1:

• Signed informed consent form (ICF) and able to comply with study requirements.
• Age ≥ 18 years (or the legal age of consent) at the time the ICF is signed.
• Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors previously treated with standard systemic therapy or for which treatment is not available or not tolerated, and who have not received prior therapy targeting TIGIT.
  • Hepatocellular carcinoma (HCC) patients require Child-Pugh A classification before the first dose of study drugs.
• ≥ 1 evaluable lesion per RECIST v1.1. 5. If available, archived, formalin-fixed paraffin-embedded (FFPE) tumor tissue sample (block or approximately 15 freshly cut unstained FFPE slides). • If archival tissue is unavailable, optional fresh baseline tumor biopsy is strongly recommended
• Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• ≥ 1 measurable lesion per RECIST v1.1.
• Has adequate organ function.
  • Absolute neutrophil count ≥ 1.5 x 10^9 /L;
  • Platelet count ≥ 100 x 10^9/L;
  • Hemoglobin ≥ 90 g/L, without blood transfusion or growth factor support ≥ 14 days before sample collection;
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation;
  • Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for patients with Gilbert syndrome);
  • Aspartate aminotransferase and alanine aminotransferase ≤ 3 x ULN.
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drugs, and have a negative urine or serum pregnancy test ≤ 7 days of the first dose of study drugs.
• Nonsterile males must be willing to use highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drugs.

Inclusion Criteria - Phase 1B:

• Signed informed consent form (ICF) and able to comply with study requirements.
• Age ≥ 18 years (or the legal age of consent) at the time the ICF is signed.
• Following determination of RP2D, the combination will be evaluated in histologically or cytologically confirmed tumor types with staging per AJCC 8th edition (Amin et al 2017) in the following disease cohorts:
  • Cohort 1: Have histologically or cytologically confirmed stage IV squamous NSCLC;
  • Cohort 2: Have histologically or cytologically confirmed stage IV non-squamous NSCLC;
  • Cohort 3: Have histologically or cytologically confirmed stage IV squamous or nonsquamous NSCLC with PD-L1 positive (TC ≥ 1%). Patients must have PD-L1 immunohistochemistry (IHC) testing with results positive (TC ≥ 1%) performed by a central laboratory during the screening period. Patients with tumors of mixed (squamous and non-squamous) or unspecified nonsmall cell histology are eligible;
  • Cohort 4: Have histologically or cytologically confirmed extensive-stage SCLC;
  • Cohort 5: Have histologically or cytologically confirmed stage IIIB, IIIC or IV NSCLC. Patients who previously treated with one or two lines of prior standard systemic therapy for locally advanced or metastatic disease. Disease progression within 6 months following completion of local therapy with curative intention including adjuvant chemotherapy after surgical procedure or concurrent chemoradiotherapy with/without consolidation could be considered as treated with one line standard systemic therapy. The best response with anti-PD-(L)1 treatment, which must be the most recent line, should be CR, PR or SD;
  • Cohort 6: Have histologically or cytologically confirmed stage IV ESCC;
  • Cohort 7: Have histologically or cytologically confirmed stage IV EAC;
  • Cohort 8: Have histologically or cytologically confirmed recurrent or metastatic HNSCC that is considered incurable by local therapies.  The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Patients must not have a primary tumor site of nasopharynx (any histology). Patients must have positive PD-L1 IHC testing results (vCPS ≥ 1%) performed by a central laboratory during the screening period.  Known p16 expression for oropharyngeal cancers by local testing. If local p16 testing results are not available, a tumor tissue sample may be submitted for p16 testing at the designated central laboratory. Oral cavity, hypopharynx, and larynx cancer are not required to undergo HPV testing by p16 IHC;
  • Cohort 9: Have histologically or cytologically confirmed stage IV G/GEJ adenocarcinoma.
• ≥ 1 measurable lesion per RECIST v1.1.
  • No prior local therapy of selected target lesion(s) OR, if prior local therapy, subsequent progression of each selected target lesion as per RECIST v1.1.
• Archived tumor tissue or fresh biopsy (FFPE block or approximately 15 freshly cut unstained FFPE slides, at least ≥ 8 slides are mandatory) are required to be collected. For Cohort 3 (NSCLC with PD-L1 positive [TC ≥ 1%]) and Cohort 8 (HNSCC with PD-L1 positive [vCPS ≥ 1%]), prospective PD-L1 IHC testing at the designated central laboratory is mandatory.
• ECOG Performance Status ≤ 1.
• Adequate organ function as indicated by the following laboratory values during screening:
  • Absolute neutrophil count ≥ 1.5 x 10^9 /L;
  • Platelet count ≥ 100 x 1^09 /L for patients receiving BGB-A1217 plus tislelizumab plus chemotherapy or ≥ 75 x 10^9 /L for patients receiving BGB-A1217 plus tislelizumab;
  • Hemoglobin ≥ 90 g/L, without blood transfusion or growth factor support ≥ 14 days before sample collection;
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula);
  • Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for patients with Gilbert syndrome);
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN or < 5 x ULN if hepatic metastases present.
• Females of childbearing potential must be willing to use a highly effective method of birth control for the course of the study through 180 days after the last dose of chemotherapeutic agents (14 months after the last dose of cisplatin; 9 months after the last dose for oxaliplatin) or through 120 days after the last dose of study drugs, and have a negative urine or serum pregnancy test ≤ 7 days of the first dose of study drugs.
• Nonsterile males must be willing to use highly effective method of birth control for the course of the study through 180 days after the last dose of chemotherapeutic agents (11 months after the last dose of cisplatin; 6 months after the last dose for oxaliplatin) or through 120 days after the last dose of study drugs.

Exclusion Criteria - Phase I:

• Active leptomeningeal disease or uncontrolled brain metastasis.
  • Patients with equivocal findings or with confirmed brain metastases are eligible if they are asymptomatic and radiologically stable without need for corticosteroids for ≥ 4 weeks before the first dose of study drugs.
• Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:
  • Controlled type 1 diabetes;
  • Hypothyroidism (provided it is managed with hormone-replacement therapy only);
  • Controlled celiac disease;
  • Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia);
  • Any other disease that is not expected to recur in the absence of external triggering factors.
• Any active malignancy ≤ 2 years before the first dose of study drugs, except for the specific cancer under investigation and any locally recurring cancer that has been treated with curative intent (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
• 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 drugs, with the following exceptions:
  • Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent);
  • Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption;
  • Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen).
• History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis, acute lung diseases, etc.
• Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥ Grade 3 hypoalbuminemia ≤ 14 days before the first dose of study drugs.
• Severe chronic or active infections (including but not limited to tuberculosis infection) requiring systemic treatment ≤ 14 days before the first dose of study drugs.
• Known history of HIV infection.
• Known history of or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection except for the following:
  • Patients with untreated chronic HBV or chronic HBV carriers whose HBV deoxyribonucleic acid (DNA) is ≥ 500 IU/mL or patients with positive HCV ribonucleic acid should be excluded. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA < 500 IU/mL), and cured hepatitis C patients (as defined by a positive HCV antibody test and negative HCV ribonucleic acid test) may be enrolled.
• Major surgical procedure, open biopsy, or significant traumatic injury ≤ 4 weeks before the first dose of study drugs or anticipation of need for major surgical procedure during the course of the study.
• Prior immunodeficiency, allogeneic stem cell transplantation, or organ transplantation.
• Any of the following cardiovascular criteria:
  • Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before the first dose of study drugs;
  • Symptomatic pulmonary embolism or other clinically significant episode of thromboembolic disease ≤ 28 days before the first dose of study drugs;
  • History of acute myocardial infarction ≤ 6 months before the first dose of study drugs;
  • History of heart failure meeting New York Heart Association Classification III or IV ≤ 6 months before the first dose of study drugs;
  • Ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before the first dose of study drugs;
  • Cerebrovascular accident ≤ 6 months before the first dose of study drugs;
  • Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days before the first dose of study drugs.
• History of severe hypersensitivity reactions to other monoclonal antibodies.
• Chemotherapy, immunotherapy (e.g., interleukin, interferon, or thymosin), or investigational therapy ≤ 14 days or 5 half-lives (whichever is shorter) before the first dose of study drugs.
  • Received any herbal medicine or Chinese patent medicines used to control cancer ≤ 14 days before the first dose of study drugs.
• Toxicities from prior therapy that have not recovered to baseline, ≤ Grade 1, or stabilized, except for AEs not considered a likely safety risk (e.g., alopecia, neuropathy, and specific laboratory abnormalities).
• Live vaccine ≤ 4 weeks before the first dose of study drugs.
  • Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
• Medical condition or alcohol or drug abuse or dependence that, in the investigator’s opinion, will be unfavorable for the administration of study drugs or will affect the explanation of drug toxicity or AEs or are likely to result in insufficient compliance with study procedures.
• Concurrent participation in another therapeutic clinical study.
• Any condition that requires treatment with prohibited or restricted concomitant medication or therapy.

Exclusion Criteria - Phase 1B:

• For Cohort 1, 2, 3, 4, and 9, patients with any prior therapy for metastatic disease, including systemic chemotherapy or local radiotherapy are excluded. If there is prior neoadjuvant/adjuvant chemotherapy, a treatment-free interval of at least 6 months prior to signing ICF is required.
• For Cohort 6, 7 and 8, patients with any prior systemic therapy for recurrent/metastatic disease are excluded. Patients with prior systemic chemotherapy administered as a part of chemoradiotherapy for locally advanced disease are eligible. If there is prior curatively intended systemic treatment, a treatment-free interval of at least 6 months prior to signing ICF is required.
• Certain types of patients are excluded:
  • For Cohort 1, 2, 3, and 5, tumors of mixed non-small cell histology will be categorized by the predominant cell type; if small cell elements are present, the patient is ineligible;
  • For Cohort 2, 3 and 5, non-squamous NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, and c-ros oncogene 1 (ROS1) fusion are excluded. All patients with non-squamous histology must have been tested locally for EGFR, ALK, and ROS1 status. Use of a FDA-approved or local Health Authority approved test is strongly encouraged, or a central laboratory test can be used if a local laboratory test is not available;
  • For Cohort 9, patients with squamous cell or undifferentiated or other histological type GC or diagnosed with gastric or GEJ adenocarcinoma with positive HER2 expression. All G/GEJ patients must have been tested locally for HER2 status. If local HER2 testing results are not available, a tumor tissue sample may be submitted to the designated central laboratory for HER2 testing.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-TIGIT or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. (anti-PD(L)1 exception for Cohort 5).
• Active leptomeningeal disease or uncontrolled brain metastasis.
  • Patients with equivocal findings or with confirmed brain metastases are eligible if they are asymptomatic and radiologically stable without need for corticosteroids for ≥ 4 weeks before the first dose of study drugs.
• Palliative radiation treatment within 4 weeks of first dose.
• For Cohort 6 and 7, patients with unintentional weight loss ≥ 5% within one month and/or CTCAE ≥ Grade 2 anorexia within 7 days prior to first dose or Nutritional Risk Index (NRI) < 83.5 per investigator’s choice. For Cohort 9, patients with weight loss ≥  20% within 2 months prior to randomization and/or CTCAE ≥ Grade 2 anorexia within 7 days prior to randomization.
• Patients with evidence of fistula (either esophageal/bronchial or esophageal/aorta).
• Evidence of complete esophageal obstruction not amenable to treatment.
• Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention).
• Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:
  • Controlled type 1 diabetes;
  • Hypothyroidism (provided it is managed with hormone-replacement therapy only);
  • Controlled celiac disease;
  • Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia);
  • Any other disease that is not expected to recur in the absence of external triggering factors.
• Any active malignancy ≤ 2 years before the first dose of study drugs, except for the specific cancer under investigation 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).
• 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 drugs, with the following exceptions:
  • Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent);
  • Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption;
  • Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen).
• History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis, acute lung diseases, etc.
• Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥ Grade 3 hypoalbuminemia ≤ 14 days before the first dose of study drugs.
• Severe chronic or active infections (including but not limited to tuberculosis infection) requiring systemic treatment ≤ 14 days before the first dose of study drugs.
• Known history of HIV infection.
• Known history of or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection except for the following:
  • Patients with untreated chronic HBV or chronic HBV carriers whose HBV deoxyribonucleic acid (DNA) is ≥ 500 IU/mL or patients with positive HCV ribonucleic acid should be excluded. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA < 500 IU/mL), and cured hepatitis C patients (as defined by a positive HCV antibody test and negative HCV ribonucleic acid test) may be enrolled.
• Major surgical procedure, open biopsy, or significant traumatic injury ≤ 4 weeks before the first dose of study drugs or anticipation of need for major surgical procedure during the course of the study.
• Prior immunodeficiency, allogeneic stem cell transplantation, or organ transplantation.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency for patients receiving 5-FU or capecitabine.
•  Any of the following cardiovascular criteria:
  • Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before the first dose of study drugs;
  • Symptomatic pulmonary embolism or other clinically significant episode of thromboembolic disease ≤ 28 days before the first dose of study drugs;
  • History of acute myocardial infarction ≤ 6 months before the first dose of study drugs;
  • History of heart failure meeting New York Heart Association Classification III or IV ≤ 6 months before the first dose of study drugs;
  • Ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before the first dose of study drugs;
  • Cerebrovascular accident ≤ 6 months before the first dose of study drugs;
  • Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg despite anti-hypertension medications ≤ 28 days before the first dose of study drugs.
• History of severe hypersensitivity reactions to other monoclonal antibodies.
• Chemotherapy, immunotherapy (e.g., interleukin, interferon, or thymosin), or investigational therapy ≤ 14 days or 5 half-lives (whichever is shorter) before the first dose of study drugs.
  • Received any herbal medicine or Chinese patent medicines used to control cancer ≤ 14 days before the first dose of study drugs.
• Toxicities from prior therapy that have not recovered to baseline, ≤ Grade 1, or stabilized, except for AEs not considered a likely safety risk (e.g., alopecia, neuropathy, and specific laboratory abnormalities).
• Live vaccine ≤ 4 weeks before the first dose of study drugs.
  • Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed;
  • A non-live COVID-19 vaccine may be administered if recommended per local practice. The vaccine administered cannot be a live or live-attenuated vaccine. For patients to accept COVID-19 vaccine during the course of the study, it is necessary to consult medical monitor.
• Medical condition or alcohol or drug abuse or dependence that, in the investigator’s opinion, will be unfavorable for the administration of study drugs or will affect the explanation of drug toxicity or AEs or are likely to result in insufficient compliance with study procedures.
• Concurrent participation in another therapeutic clinical study.
• Any condition that requires treatment with prohibited or restricted concomitant medication or therapy.
• Patients not suitable for chemotherapy or immunotherapy; e.g., serious immune mediated adverse events in previous immunotherapy if any, per investigator’s discretion for cohorts in Phase 1b.
• Patients receiving paclitaxel must not have peripheral neuropathy ≥ Grade 2 at baseline.

Eligibility last updated 9/16/21. Questions regarding updates should be directed to the study team contact.