Dostarlimab in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability–high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC): The GARNET study.

Authors

Ana Oaknin

Ana Oaknin

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

Organizations

Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, and Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, New York University School of Medicine, New York, NY, McGill University Health Centre, Royal Victoria Hospital, Montréal, QC, Canada, Department of Medical Oncology, Institut Paoli Calmettes, Marseille, France, Georgia Cancer Center, Augusta University, Augusta, GA, S.C. Sperimentazioni Cliniche Istituto Nazionale Tumori di Napoli IRCCS - Fondazione, Naples, Italy, START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, National Cancer Research Institute (NCRI), London, United Kingdom, BC Cancer-Vancouver, Vancouver, BC, Canada, Regional Center of Oncology, Gdansk, Poland, Karyopharm Therapeutics, Newton, MA, GlaxoSmithKline, Pennington, NJ, GlaxoSmithKline, Cambridge, MA, GlaxoSmithKline, London, United Kingdom, Dana Farber Cancer Institute, Boston, MA, British Columbia Cancer Agency, Vancouver, BC, Canada, Washington University School of Medicine in St. Louis, St. Louis, MO

Research Funding

Pharmaceutical/Biotech Company

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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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Clinical Science Symposium

Session Title

Molecular-Based Treatment for Endometrial Cancer

Track

Gynecologic Cancer

Sub Track

Uterine Cancer

Clinical Trial Registration Number

NCT02715284

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 5509)

DOI

10.1200/JCO.2022.40.16_suppl.5509

Abstract #

5509

Abstract Disclosures