LAUSR

TPS4145 Background: Although checkpoint inhibitors (CPIs) can produce durable responses in gastric cancer patients (pts) in the 3rd line setting, the response rate is only 10-15%. Therefore, there is a huge unmet need to enhance the response rate of CPIs to provide benefit to wide range of pts. A novel concept in immuno-oncology is the use of cancer specific oncolytic viral therapy. In addition to the specific killing of the tumor by the virus, these agents can induce an immunogenic cell death in the tumor to augment the immune activation driven by PD-1 inhibition. OBP-301 is an oncolytic adenovirus genetically modified to be able to selectively replicate in cancer cells by introducing human telomerase reverse transcriptase (hTERT) promoter. Results of a phase I study of OBP-301 in solid tumor pts demonstrated the safety and efficacy of intra-tumoral injection of OBP-301. A pre-clinical study of the combination of OBP-301 with anti-PD-1 antibody has also shown significant synergistic activity as well. Based on these encouraging pre-clinical and clinical data, we designed a phase II clinical trial to examine the safety and efficacy of combination of pembrolizumab and OBP-301 in the treatment of PD-L1 positive metastatic gastric/GEJ adenocarcinoma. Methods: This is a multicenter, non-randomized phase II trial of OBP-301 with pembrolizumab in metastatic gastric/GEJ adenocarcinoma that has progressed on at least 2 lines of prior therapy. Eligibility criteria include PD-L1 positive tumors as defined by a combined positive score, performance status ≤1, and good end organ function. The primary endpoints are to examine objective response rate and safety of OBP-301 with pembrolizumab. The secondary endpoints are to examine disease control rate, duration of response, overall survival and progression free survival. Correlative studies are planned to identify biomarkers for response to combination therapy by using multiparameter flowcytometry, single-cell transcriptional profiling and immunohistochemistry. All eligible pts will receive 1x1012Viral Particles/mL of OBP-301 administered every 2 weeks for total of 4 injections, injected directly into tumor via upper endoscopy. Every pt will also receive pembrolizumab 200 mg IV every 3 weeks for 2 years or until progression. Pts will be enrolled in a Simon two stage design, with 18 pts in the first stage. If 3 or more pts respond to the combination therapy, the study will move forward to stage 2, with 19 more pts enrolled. The study is currently enrolling pts.