Anti PD-1 monoclonal antibody in patients with MSI-high and/or high tumor mutational burden for solid malignancies.

e15539 Background: High microsatellite instability (MSI-H) tumors have been associated with good responses to check-point inhibitors (CPI). With overall response rates (ORR) ranging between 36-46% among colorectal cancer (CRC) and other solid malignancies. Data regarding predictors of response and responses in non-CRC malignancies remains limited. We sought to evaluate the response to PD-1/PDL-1 CPI in patients with MSI-H and/or high TMB solid malignancies. Methods: Retrospective analysis of 16 patients (pts) who received 18 CPI-based therapies between October 2017 and February 2022. MSI-H and TMB status was assessed by CARIS, Guardant360 or INVITAE genetic testing. Primary objective was to determine objective response rate (ORR), defined as complete response (CR) or partial response (PR) by RECIST1.1. Secondary outcomes included progression-free survival(PFS); overall survival (OS), and duration of overall response (DOR). Results: A total of 16 pts were included. The median age of 72 years (range 53-83), 44% were male and 75% Hispanic. 44% of pts had RCR and 50% were previously treated, and 50% were stage IV at diagnosis. The most common mutations were BRCA2 31%, PIK3cA 31%, KRAS 25%, and GNAS 25%. The majority of pts received single-agent CPI therapy (72%). After a median follow-up of 52 months, 11 pts continued to receive therapy, 2 pts completed treatment. 3 pts died from progression of the disease. 1 pts switched from single-agent pembrolizumab to nivolumab-ipilimumab combination followed by nivolumab maintenance due to disease progression. 15 pts were evaluable for response with an ORR of 33%, including 33% among pts with CRC and 27% for non-CRC malignancies. (Table - Response rates) The OS was not reached (NR), with a PFS of 53 months (PFS of 64% at 1 year and 56% at 4 years). The median DOR was not reached (NR). The treatment was well tolerated and pts received a median of cycles was 19 (range 3-51) with no discontinuations due to toxicities. The molecular mutations, clinical characteristics, type of malignancy, MSI-H, or H-TMB status were not significantly associated with response to CPI after logistical regression analysis. Conclusions: CPIs are an effective treatment option for patients with MSI-H and/or High TMB, with an ORR of 33%. However, pts achieved durable responses, with a median DOR not reached. We identify a higher incidence of SD rates among CRC pts (67% vs. 18% non-CRC). We did not identify any predictors associated with response to CPI, likely due to the small number of pts. However, there was a tendency to highest response rates among pts with MSI-H and high TMB.[Table: see text]