An Open Label, Single-Arm, Multi-center Phase II Study to Evaluate the Safety and Efficacy of Tislelizumab in Combination With Zanidatamab as a 2nd Line in HER2-Positive Advanced Gastric Cancer in K-Umbrella Trial

Study Design:

This is a Phase II study to assess the safety and clinical efficacy of this combined chemotherapy-free regimen (zanidatamab and tislelizumab) in HER2-positive advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma after first line treatment. The study will be conducted as phase II study to evaluate the safety and tolerability of the combination treatment of zanidatamab and tislelizumab and determine anti-tumor activity in HER2-positive advanced gastric/GEJ adenocarcinoma patients. This study will be conducted at up to 6 medical centers in Korea. Patients who are HER2-positive will be confirmed by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH)/silver in situ hybridization (SISH) at local laboratory. Patients who meet all eligibility criteria will be enrolled to this study and receive treatment with zanidatamab and tislelizumab until progressive disease is confirmed or at least 1 discontinuation criterion is met.

Study Assessments:

Patients will be monitored for safety, tolerability, and antitumor activity throughout the study. Safety will be assessed throughout the study by monitoring AEs/SAEs, and laboratory results. Vital signs, physical examinations, Eastern Cooperative Oncology Group (ECOG) performance status change, ECG results, echocardiogram/MUGA, and other examinations will also be used for safety assessment. Anticancer activity will be evaluated by the investigator using RECIST 1.1. Radiological assessment of tumor response status will be performed every 6 weeks (±7 days) from (anchored to) Cycle 1 Day 1 for the first 54 weeks and every 12 weeks (±7 days) thereafter until disease progression, withdrawal of consent, death, or start of a new anticancer therapy.

Patients who discontinue study treatment early for reasons other than disease progression will continue to undergo tumor assessments following the original plan until the patient begins a subsequent anticancer treatment, experiences disease progression, withdraws consent, is lost to follow up, death, or until the study terminates, whichever occurs first.

Duration of Patient Participation:

Screening Period is within 28 days prior to the first dose of study drug. Treatment Period starts with the first dose administration of study drug and ends when the patient is discontinued for study treatment when they are no longer considered to be achieving clinical benefit due to confirmed disease progression or unacceptable toxicity, or due to death or withdrawal of consent.

Safety Follow-up. Patients who discontinue treatment for any reason will be asked to return to the clinic for the Safety Follow up Visit (to occur approximately 30 days (±7 days] after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first). In addition, telephone contacts with patients treated with zanidatamab and tislelizumab should be conducted to assess immune-mediated AEs and concomitant medications (if applicable, i.e. associated with an immune-mediated AE or is a new anticancer therapy) at 60 (±14 days) and 90 days (±14 days) after the last dose of study drug(s) regardless of whether the patient starts a new anticancer therapy.

Survival Follow-up. Patients will be followed for survival and further anticancer therapy information after discontinuation of study treatment via telephone calls, patient medical records, and/or clinic visits approximately every 3 months (±14 days) after the Safety Follow-up Visit or as directed by the investigator until death, loss to follow-up, withdrawal of consent, or study completion.