1393P Phase I/II clinical trial of combination of anti-PD-1 mAb, nivolumab with radiotherapy for unresectable and recurrent gastric cancer who failed to standard chemotherapy

Although basic, translational and clinical research suggest a possibility of synergistic effect of radiation-induced immunogenic cell death with immune checkpoint inhibitors, the effectiveness of concurrent therapy with radiotherapy and immunotherapy is not fully established. Phase I/II, open single arm, prospective clinical trial was conducted and eligible patients were unresectable advanced or recurrent gastric cancer patients (n = 40) who developed progression after primary and secondary chemotherapy with multiple metastasis assessable in imaging (one lesion must be ≥2cm). Radiotherapy of total 22.5 Gy/5 fractions/5 days was given to the largest or symptomatic lesion and nivolumab was administered day 15-22 at 3 mg/kg or 240mg/body every 2 weeks to a total of 6 administrations. The primary endpoint is disease control rate of non-irradiated lesions as an abscopal effect. The secondary endpoints are MST, safety and proportion of local control rate for irradiated lesion. As an ancillary analysis, immunologic parameters including high-dimensional MHC multimer analysis and TCR repertoire analysis, and ctDNA analysis are designed. Total 41 patients were enrolled and 40 patients were evaluated as full analysis set, since 1 patient was judged as an unmatched case to inclusion criteria. The clinical evaluation as an abscopal effect were CR=1 (2.5%), PR=5 (12.5%), SD=3 (7.5%), PD=15 (37.5%) and NE=16 (40%). The disease control rate and the response rate for non-irradiated target lesions was 22.5% and 15%, respectively. The MST was 230 days (157-330, 95%CI) and 1-year survival rate was 28.6%. Any adverse event more than Grade 3 was observed in 16 cases in 41 patients (39%). The most frequent AE more than grade 3 were anemia (19%) and appetite loss (12%). The local control for irradiated lesions were seen in CR=5 (12.5%), PR=6 (15%), SD=5 (12.5%), PD=4 (10%) and NE=20 (50%). The ancillary analysis for immunological monitoring is under investigation. The combination of nivolumab with radiotherapy demonstrated promising anti-tumor activity with marked prolonged survival time in gastric cancer. No new safety issues were detected in the combination.