Abstract 5135: Antitumor activity of dostarlimab by PD-L1 and tumor mutation burden (TMB) in patients (pts) with mismatch repair deficient and proficient (dMMR and MMRp) tumors in the GARNET trial

Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved as monotherapy in pts with dMMR recurrent/advanced endometrial cancer (EC) that has progressed on or following treatment with a platinum-containing regimen or solid tumors that have progressed on or following prior treatment, with no satisfactory alternative treatment options. Here we report on a post-hoc analysis of antitumor activity by PDL1 expression and TMB in pts with dMMR and MMRp solid tumors in the GARNET trial. Methods: GARNET (NCT02715284) is a phase 1, multicenter, open-label, single-arm study of dostarlimab in pts with advanced/recurrent solid tumors. Three expansion cohorts enrolled pts based on MMR status: dMMR (A1) and MMRp (A2) advanced/recurrent EC, and dMMR non-EC solid tumors (F). Pts received dostarlimab 500 mg IV Q3W for 4 cycles, then 1000 mg IV Q6W until progression or discontinuation. TMB and PDL1 were exploratory biomarkers. TMB status was determined by Foundation One test; TMB-high (TMB-H) was defined as ≥10 mutations/Mb. PDL1 expression was determined by combined positive score (CPS) by Ventana assay; PDL1-high (PDL1-H) was defined as CPS ≥1. The study was not powered to assess antitumor activity within subgroups. Results: TMB-H and PDL1-H were common in dMMR solid tumors; PDL1-H was observed in 39.4% of MMRp EC tumors (Table). Objective response rate (ORR) was higher in pts with TMB-H/PDL1-H tumors (55.6% for all cohorts, combined; Table). Safety for each cohort was previously reported.1 Conclusions: PDL1-H and TMB-H were frequently observed in the dMMR EC and non-EC cohorts, regardless of tumor type; PDL1-H was also prevalent in MMRp EC tumors. Although not powered to assess antitumor activity, ORR by BICR per RECIST v1.1 was higher in pts with TMB-H and PDL1-H solid tumors. Across cohorts, dMMR status was predictive of response. 1.Andre T, et al. Ann Oncol 2021;32(suppl 5):S829-S866. 991P. Table A1(dMMR EC)N=103 F(dMMR non-EC)N=106 A1+F(dMMR combined)N=209 A2(MMRp EC)N=142 A1+A2+F (Total)N=351 Biomarker distribution, n (%) TMB High 85 (82.5) 79 (74.5) 164 (78.5) 9 (6.3) 173 (49.3) Low 13 (12.6) 9 (8.5) 22 (10.5) 129 (90.8) 151 (43.0) Unknown 5 (4.9) 18 (17.0) 23 (11.0) 4 (2.8) 27 (7.7) PD-L1 High 56 (54.4) 52 (49.1) 108 (51.7) 56 (39.4) 164 (46.7) Low 23 (22.3) 17 (16.0) 40 (19.1) 45 (31.7) 85 (24.2) Unknown 24 (23.3) 37 (34.9) 61 (29.2) 41 (28.9) 102 (29.1) ORR by BICR per RECIST v1.1, n/N (%, 95% CI)a Overall 46/103(44.7, 34.9–54.8) 41/106(38.7, 29.4–48.6) 87/209(41.6, 34.9–48.6) 19/142(13.4, 8.3–20.1) — TMB-L/PDL1-L (L/L) 1/5(20.0, 0.5–71.6) 1/3 (33.3, 0.8–90.6) 2/8(25.0, 3.2–65.1) 2/43(4.7, 0.6–15.8) 4/51(7.8, 2.2–18.9) TMB-L/PDL1-H (L/H) 2/5(40.0, 5.3–85.3) 1/2(50.0, 1.3–98.7) 3/7(42.9, 9.9–81.6) 7/50(14.0, 5.8–26.7) 10/57(17.5, 8.7–29.9) TMB-H/PDL1-L (H/L) 5/17(29.4, 10.3–56.0) 3/14(21.4, 4.7–50.8) 8/31(25.8, 11.9–44.6) 0/1(0, 0–97.5) 8/32(25.0, 11.5–43.4) TMB-H/PDL1-H (H/H) 29/50(58.0, 43.2–71.8) 22/43(51.2, 35.5–66.7) 51/93(54.8, 44.2–65.2) 4/6(66.7, 22.3–95.7) 55/99(55.6, 45.2–65.5) aOnly those pts with both known TMB status and known CPS were included in ORR calculations Citation Format: Thierry André, Susana Banerjee, Dominique Berton, Susan L. Ellard, Begoña Jimenez, Vanessa Samouëlian, Lucy Gilbert, Valentina Boni, Xinwei Han, Grace Antony, Jennifer Veneris, Ana Oaknin. Antitumor activity of dostarlimab by PD-L1 and tumor mutation burden (TMB) in patients (pts) with mismatch repair deficient and proficient (dMMR and MMRp) tumors in the GARNET trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5135.