10-year follow up of a phase 2 clinical trial of pembrolizumab (pembro) in microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors.

4019 Background: Inhibitors of Programmed Cell Death Protein-1 (PD-1) have demonstrated remarkable activity in dMMR/MSI-H cancers, leading to the first tissue agnostic FDA approval for an oncologic indication. We report herein results of long-term follow up of KEYNOTE-016, the first study to demonstrate pan-tumor activity of the PD-1 inhibitor pembro in dMMR/MSI-H solid tumors. Methods: KEYNOTE-016 was a multi-center open-label phase 2 study evaluating pembro in patients with advanced colorectal cancer (CRC) (Cohort A) or non-CRC solid tumors (Cohort C) that were dMMR and had progressed after ≥1 prior line of therapy (or ≥2 prior lines for CRC). Eligible patients were age ≥ 18, and had measurable disease per RECIST 1.1. Patients with active CNS metastases, who were on immunosuppressive therapy, had autoimmune disease, or were previously treated with immune checkpoint inhibitors were excluded. Patients received pembro IV every 2 weeks until progression, intolerance, withdrawal of consent or up to a maximum of 2 years. Results: Between 9/2013 - 9/2017, 88 patients (Cohort A: 41; Cohort C: 47) enrolled at 7 sites and received ≥1 dose of pembro. Tumor types enrolled on Cohort C included endometrial (N = 15), pancreatic (N = 9), small intestinal (N = 5), gastroesophageal (N = 5), biliary (N = 4), ampullary (N = 4), and other (N = 5). Median follow up time was 49.7 mos for all patients and 99.8 mos for alive patients. Objective response rate (ORR) was 58% with 23 partial (PR) and 28 complete responses (CR). 16 patients experienced a best response of stable disease (SD) for a disease control rate of 76%. Median PFS and OS were 34.9 mos (95% CI: 14.8-NR) and 80.8 mos (95% CI: 33.2-NR) respectively. The 3-, 5-, and 10-year OS rates were 55.1%, 53.7% and 47.4% respectively. Outcomes were similar between Cohorts A and C (see Table). Conclusions: In summary, long term follow up of KEYNOTE-016 confirms high rates of durable remission from pembro in patients with dMMR/MSI-H solid tumors, with several patients remaining alive and in remission at 10+ years follow up. Responses were seen across tumor types. Clinical trial information: NCT01876511 . Results by cohort. Cohort ACRCN=41 Cohort Cnon-CRC N=47 ORR, % 56.1 59.6 PR, N (%) 11 (27) 12 (25) CR, N (%) 12* (29) 16 (34) SD, N (%) 10 (24) 6 (13) PD, N (%) 5 (12) 9 (19) NE, N (%) 3 (7) 4 (9) PFS, median months (95% CI) 38.8 (8.1-NR) 20.5 (14.3-NR) OS, median months (95% CI) 80.8 (33.2-NR) 86.4 (21.8-NR) Follow up time, median months 51.2 35.9 3-year OS rate (%) 60.5 50.3 5-year OS rate (%) 57.5 50.3 10-year OS rate (%) 47.3 47.2 *Includes 3 patients with unconfirmed CR.