Analysis of the immune-related endpoints of the mismatch repair–deficient non-endometrial solid cancers cohort from the GARNET study

Background Dostarlimab is a humanized monoclonal antibody that binds the programmed cell death protein 1 (PD-1) receptor and blocks interaction with its ligands PD-L1 and PD-L2. The GARNET (NCT02715284) trial is assessing antitumor activity and safety of dostarlimab in patients with advanced solid tumors. Here, we report efficacy endpoints by irRECIST, based on investigator assessment (IA) for the non-endometrial cancer (NEC) mismatch repair–deficient (dMMR) cohort. Methods GARNET is a multicenter, open-label, single-arm, dose-escalation and cohort expansion study. Cohort F of the GARNET trial enrolled patients with dMMR or POLε-mutated (POLε-m) solid tumors of non-endometrial origin. Patients must have progression per blinded independent central review (BICR) following prior systemic therapy with either advanced or recurrent disease, had 2 scans demonstrating an increase in tumor measurement that met the criteria for progressive disease based of RECIST v1.1, and had dMMR status assessed by immunohistochemistry (IHC). Patients received 500 mg dostarlimab IV Q3W for 4 cycles, then 1000 mg Q6W until disease progression, discontinuation, or withdrawal. The prespecified secondary endpoints of immune-related objective response rate (irORR) and immune-related duration of response (irDOR) by irRECIST are based on IA. Results The secondary efficacy analysis includes 110 patients with dMMR by IHC who had measurable disease at baseline by IA, and sufficient follow-up time (>6 months), including 3 patients with POLε-m solid tumors. The majority of patients, 102 (92.7%), had gastrointestinal tumors; 71 (64.6%) had colorectal cancer. Confirmed irORR was observed in 50 (45.5%) dMMR patients, which included 2 patients with POLε-m. Immune-related complete response (irCR) was seen in 6 (5.5%) patients, and immune-related partial response (irPR) was observed in 44 (40.0%) patients. Immune-related disease control rate was 70% (77 patients; includes irCR, irPR, or immune-related stable disease). At the data cutoff date, 44 (88.0%) responders had an ongoing response. With a median follow-up of 12.4 months, median irDOR for responders had not been reached as of the data cutoff date of March 1, 2020. Safety for this cohort has been reported previously. 1 Conclusions Dostarlimab demonstrated durable antitumor activity by irRECIST per IA across multiple tumor types. Results were consistent with the primary endpoint, RECIST v1.1 by BICR analysis. This cohort is open for further enrollment. 1. Andre T, et al. J Clin Oncol. 2021;39(suppl 3):abstract 9. Clinical trial identification NCT02715284. Editorial acknowledgement Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline, was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA). Legal entity responsible for the study The author. Funding This study (NCT02715284) was sponsored by GlaxoSmithKline, Waltham, MA, USA. Disclosure T. André: Honoraria (self): BMS, MSD Oncology, GSK; Advisory / Consultancy: BMS, MSD Oncology, GSK; Research grant / Funding (institution): BMS, MSD Oncology, GSK Travel / Accommodation / Expenses: BMS, MSD Oncology. G. Curigliano: Advisory / Consultancy: Roche, BMS, Pfizer, Seattle Genetics and Ellipsis. H. Arkenau: Honoraria (Institution): Roche, Guardant Health, Bicycle Therapeutics, Servier, Merck KGaA, BeiGene and Bayer; Advisory / Consultancy: iOncologi; Research grant / Funding (institution): Sarah Cannon Research Institute. J. Trigo: Advisory / Consultancy: AstraZeneca, BMS, MSD, Takeda and Boehringer; Research grant / Funding (institution): AstraZeneca and MSD. S. Ellard: Shareholder / Stockholder / Stock options: GlaxoSmithKline. V. Moreno: Advisory / Consultancy: BMS, Bayer, Pieris and Janssen. S. Kumar: Full / Part-time employment: GlaxoSmithKline. W. Guo: Full / Part-time employment: Employed by GlaxoSmithKline when the study was conducted. E. Im: Full / Part-time employment: GlaxoSmithKline. N. Starling: Honoraria (Institution): Eli Lilly, Merck Serono, MSD Oncology, Pierre Fabre and Servier; Research grant / Funding (institution): AstraZeneca, BMS, Pfizer; Travel / Accommodation / Expenses: AstraZeneca, BMS, Eli Lilly, MSD Oncology, Roche, and Merck. All other authors have declared no conflicts of interest.