Durvalumab + tremelimumab in biologically selected advanced/metastatic solid tumors.

2604 Background: Tremelimumab (T) in combination with Durvalumab (D) is approved by the FDA for the treatment of unresectable hepatocellular carcinoma and metastatic non–small cell lung cancer. We prospectively examined its clinical activity in a cohort of biologically-selected advanced/metastatic solid tumors from the MOST Plus clinical trial (NCT NCT02029001). Methods: Adult patients (pts) previously treated by at least one prior line but immunotherapy-naive were eligible if their tumor harbored TMB-H (>10mut/Mb) and/or MSI/dMMR (by PCR and IHC tests), and/or PD1/PD-L1/CTLA4 amplification and/or POLD1 or POLE mutation. T was administered for up to 4 cycles (75mg, IV, Q4W) and D (1500mg, IV, Q4W) until disease progression, unacceptable toxicity or patient/investigator decision. Tumor response was assessed as per RECIST 1.1 and adverse events reported according to NCI-CTCAE v4.03. Results: 70 patients were enrolled (24 male, median age: 65 years [33-88], MSI n=56, TMB-H n=10, PDL1 and PDL2 ampl. n=1, POLE mut. n=1, MSH6 mut. n=1, MSH2 mut. n=1). The median number of prior lines of systemic therapy was 1 (range: 0-4). Main tumor types were colorectal (44%), endometrial (19%), and stomach (7%) carcinomas. As of October 2022, overall response (ORR) rate was 52.8% (21.4% CR, 31.4% PR). With a median follow-up of 37 months, median PFS and OS were 8.4 months [95% CI: 4.4- 22.1] and 37.2 months [95% CI: 10.4-NE], respectively. Median duration response of response was not reached. Overall, 24.3% of patients experienced at least one serious treatment-related (TR) adverse event. Two TR-deaths were reported (haemophagocytic lymphohistiocytosis and nephritis). ORR, median PFS and OS are reported. Conclusions: T+D is a highly efficient combination in biologically selected tumors leading to a high complete response rate. Enrolment is still ongoing, to further evaluate the utility of a maintenance treatment, i.e the optimal treatment duration. Clinical trial information: NCT02029001 . [Table: see text]