Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, and Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
Ana Oaknin , Bhavana Pothuri , Lucy Gilbert , Renaud Sabatier , Sharad A. Ghamande , Adriano Gravina , Emiliano Calvo , Susana N. Banerjee , Rowan Miller , Joanna Pikiel , Mansoor Raza Mirza , Tao Duan , Sybil Zildjian , Eleftherios Zografos , Jennifer Taylor Veneris , Anna Tinker , Matthew A. Powell
Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the U.S. as a monotherapy in patients (pts) with dMMR AR EC that has progressed on or after treatment with a platinum-containing regimen or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options; and in the E.U. as a monotherapy in pts with dMMR/MSI-H AR EC that has progressed on or after treatment with a platinum-containing regimen. Here, we report on efficacy and safety in the 2 expansion cohorts of the GARNET trial that enrolled pts with EC. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or cohort A2 (MMRp/MSS EC) based on local assessment. Pts received 500 mg of dostarlimab IV Q3W for 4 cycles, then 1,000 mg Q6W until disease progression, discontinuation, or withdrawal. The primary endpoints are ORR and DOR by blinded independent central review using RECIST v1.1. Results: For this third interim analysis, 153 dMMR/MSI-H and 161 MMRp/MSS pts were enrolled and dosed. Of these, 143 dMMR/MSI-H and 156 MMRp/MSS pts had measurable disease at baseline and ≥ 6 mo of follow-up and were included in the efficacy-evaluable population. ORRs were 45.5% (dMMR/MSI-H) and 15.4% (MMRp/MSS; Table). Median (m) DORs were not reached (NR; dMMR/MSI-H) and 19.4 mo (MMRp/MSS). Probability of PFS at 6, 9, and 12 mo was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 35.8%, 31.3%, and 29.4% in MMRp/MSS EC, respectively. mOS was NR (dMMR/MSI-H) and 16.9 mo (MMRp/MSS). Overall, 27 pts (8.6%) discontinued treatment because of a treatment-related adverse event (TRAE; 13 dMMR/MSI-H, 14 MMRp/MSS). The majority of TRAEs were grade 1 or 2. The most common any-grade TRAEs were fatigue (56; 17.8%), diarrhea (46; 14.6%), and nausea (43; 13.7%). No deaths were attributed to dostarlimab in the EC cohorts. Hypothyroidism (12; 8%) was the most common any-grade immune-related TRAE. Conclusions: Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with better outcomes: a higher response rate and longer PFS and OS. Safety was consistent with other PD-1 antibodies. Clinical trial information: NCT02715284.
dMMR/MSI-H EC N=143 | MMRp/MSS EC N=156 | |
---|---|---|
Median follow-up time, mo | 27.6 | 33.0 |
ORR, n (%, 95% CI) Complete response, n (%) Partial response, n (%) | 65 (45.5, 37.1–54.0) 23 (16.1) 42 (29.4) | 24 (15.4, 10.1–22.0) 4 (2.6) 20 (12.8) |
Disease control rate, n (%, 95% CI) | 86 (60.1, 51.6–68.2) | 53 (34.0, 26.6–42.0) |
Response ongoing, n (%) | 54 (83.1) | 9 (37.5) |
mDOR (range), mo | NR (1.18+ to 47.21+) | 19.4 (2.8–47.18+) |
mPFS (95% CI), mo | 6.0 (4.1–18.0) | 2.7 (2.6–2.8) |
Estimated probability of PFS, % (95% CI) 6 mo 9 mo 12 mo | 49.5 (41.0–57.5) 48.0 (39.4–56.0) 46.4 (37.8–54.5) | 22.9 (16.5–30.0) 15.5 (10.1–22.0) 13.3 (8.3–19.5) |
mOS (95% CI), mo | NR (25.7–NR) | 16.9 (13.0–21.8) |
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