Abstract 1393P
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
NCT03453164.
Editorial acknowledgement
Legal entity responsible for the study
Clinical Research Center, Fukushima Medical University Hospital; Clinical Research Center, Kanagawa Cancer Center Hospital.
Funding
Ono Pharmaceutical company.
Disclosure
K. Kono: Financial Interests, Institutional, Sponsor/Funding: Ono Pharmaceutical company; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical company. K. Mimura: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical company. T. Ogata: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical company. T. Yamada: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical company. H. Katoh: Financial Interests, Institutional, Research Grant: KOWA electric industry. Y. Suzuki: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical company; Financial Interests, Personal, Advisory Board: Chugai Pharmacetical; Financial Interests, Personal, Advisory Board: Kyowa Kirin. All other authors have declared no conflicts of interest.