Dostarlimab Provides Long-Term Benefits in dMMR/MSI-H Endometrial Cancer

Dostarlimab-gxly (Jemperli) monotherapy maintained durable antitumor in patients with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) advanced or recurrent endometrial cancer, according to 6-year follow-up data from cohort A1 of the phase 1 GARNET trial (NCT02715284) presented at the 2026 ESMO Gynaecological Cancers Annual Congress.¹

At a median follow-up of 69.0 months, dostarlimab (n = 143) induced an objective response rate (ORR) of 45.5% (95% CI, 37.1%-54.0%), which was unchanged from the prior analysis at a median follow-up of 27.6 months.^1,2 The complete response (CR) rate deepened from 16.1% to 22.4% over the additional 41 months of follow-up; the partial response (PR) rate was 23.1%, and the disease control rate (DCR) held at 60.1% (95% CI, 51.6%-68.2%).

The median duration of response (DOR) was not reached (NR; 95% CI, 1.2-85.6+), with 2-, 4-, and 6-year DOR rates of 85.1%, 81.3%, and 73.1%, respectively. The median overall survival (OS) was also NR (95% CI, 23.8-not evaluable). The OS rate at 2 years was 58.2%; the 4-year rate was 52.9%, and the 6-year rate was 50.1%.

“The 6-year follow-up confirms the high rate of durable remission offered by dostarlimab in the GARNET trial. Neither the median DOR nor the median OS was reached at a median follow-up of 69 months. A continued deepening of response over time, characterized by a meaningful increase in complete responses, was seen,” said presenting author Bhavana Pothuri, MD. “Collectively, these robust data reinforce dostarlimab monotherapy as a highly effective standard-of-care treatment option for patients with dMMR/MSI- advanced recurrent endometrial cancer who have progressed following prior platinum-based therapy.

Pothuri is a gynecologic oncologist at NYU Langone Health and the Laura & Isaac Perlmutter Cancer Center in New York, New York.

Why do the 6-year GARNET data matter in pretreated dMMR/MSI-H endometrial cancer?

GARNET is the largest evaluation of PD-(L)1 monotherapy in platinum-exposed patients with dMMR/MSI-H advanced or recurrent endometrial cancer.^1,2 “Historically, these patients have faced an exceptionally poor prognosis with overall survival of less than 12 months,” Pothuri said.

Earlier data from the trial showed that the agent induced an ORR of 42.3% in evaluable patients (n = 71); this included a CR rate of 12.7% and a PR rate of 29.6%.² The DOR was at least 6 months for 93.3% of responders, and the median DOR was NR at a median follow-up of 14.1 months (2.6-22.4+). These data supported the FDA accelerated approval of dostarlimab for use in patients with recurrent or advanced endometrial cancer that has progressed on or after previous treatment with a platinum-containing chemotherapy and whose cancers are dMMR, as determined by an FDA-approved test.

At the time of the approval, Lucy Gilbert, MD, MSc,³ told OncLive® in an exclusive interview:⁴ “This is something we have been waiting ages for because women with recurrent endometrial cancer, once they’ve failed platinum-based chemotherapy, [we] have next to nothing,” she said, “This is hugely important for women with recurrent endometrial cancer and for gynecologic oncologists and medical oncologists because it gives us something where we had nothing before.”

At a median follow-up of 27.6 months, the ORR was 45.5% in those with dMMR/MSI-H endometrial cancer (n = 65); the median DOR was still NR.^5,6

The 6-year analysis adds extended efficacy and safety data plus a conditional survival analysis to inform long-term prognosis.¹

How was the GARNET trial designed, and who was enrolled?

GARNET is a phase 1, multicenter, open-label, single-arm study of dostarlimab monotherapy in patients with advanced or recurrent solid tumors; cohort A1 enrolled patients with dMMR/MSI-H EC identified by mismatch repair status by immunohistochemistry or PCR/NGS microsatellite instability assessment.

Patients received 500 mg of intravenous dostarlimab every 3 weeks for 4 cycles, then 1000 mg every 6 weeks for up to 2 years until disease progression, discontinuation, or withdrawal. Treatment beyond 2 years was allowed after investigator-sponsor discussion. The primary objective was antitumor activity by ORR and DOR per blinded independent central review using RECIST v1.1.

Among the 143 patients in the efficacy population, the median age was 65 years (range, 39-85); 56.6% had FIGO stage III or IV disease at diagnosis. In terms of histology, 64.3% had grade 1 or 2 endometrioid carcinoma, 14.7% had grade 3 endometrioid histology, and 4.9% had serous tumors. All patients had received prior anticancer therapy; 37.1% had received at least 2 prior lines, and 70.6% had received previous radiation.

What were the additional efficacy outcomes with dostarlimab at 6 years?

“Remarkably, the median DOR has still not been reached,” Pothuri said. “We observed a clear plateau in the Kaplan-Meier curve, yielding a 6-year DOR rate of 73%. This beautifully illustrates the durable nature of this benefit, with a median survival follow-up of 69 months.”

Although the protocol permitted patients who remained progression free to discontinue dostarlimab at 2 years, many continued beyond that point. Among progression-free patients, 76.5% remained on dostarlimab during year 2 to 3, 75.0% during year 3 to 4, 61.9% during year 4 to 5, 58.6% during year 5 to 6, and 61.5% during year 6+.

What did the conditional overall survival analysis show?

“In clinical practice, patients who are doing well on treatment often ask us about their long-term prognosis. This is where conditional OS becomes an invaluable tool,” Pothuri said. “Unlike traditional survival estimates, which are calculated from day 1 of a trial, the conditional OS measures the probability of surviving at an additional period of time, given that a patient has already survived to a specific landmark of 1, 2, or 3 years. This provides us with much more relevant real-world data for patient counseling.”

From the 1-year landmark, the 5-year survival probability was 68.9% (95% CI, 58.4%-77.2%); from the 2-year landmark, the 4-year survival probability was 86.0% (95% CI, 75.2%-92.4%); and from the 3-year landmark, the 3-year survival probability was 88.3% (95% CI, 77.5%-94.1%).

“When we look at the conditional estimates for our dMMR/MSI-H endometrial cancer cohort, these data are incredibly encouraging,” Pothuri said. “If a patient is alive at 2 years after initiating dostarlimab at the 2-year landmark, the probability they will remain alive at 6 years is remarkably high, at 86%.”

What was the safety profile of dostarlimab at 6 years?

No new safety signals emerged with 6 years of follow-up in the 153-patient safety population, and treatment-related adverse effect (TRAE) incidence remained low throughout the study.

The most common any-grade TRAEs were diarrhea (17.0%), asthenia (15.7%), pruritus (15.7%), arthralgia (13.7%), and fatigue (13.7%). The most common grade 3 or higher TRAEs were anemia (5.2%), increased alanine aminotransferase level (2.6%), arthralgia (2.0%), diarrhea (2.0%), and increased lipase (2.0%). Most toxicities occurred early in the treatment course, and the incidence of immune-related adverse effects remained low despite extended treatment.

“In conclusion, the 6-year follow-up confirms the high rate of durable remission offered by dostarlimab in the GARNET trial,” Pothuri said.

Disclosures: Pothuri reported institutional research support from Acrivon Therapeutics, Agenus, Alkermes, AstraZeneca, Celgene/Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo, DualityBio, Eisai, I-Mab Biopharma, ImmunoGen/AbbVie, Imunon, Incyte, Karyopharm Therapeutics, LOXO Oncology/Lilly, Mersana Therapeutics, MSD, Onconova Therapeutics/Traws Pharma, Pfizer, Roche/Genentech, Seagen/Pfizer, Sutro Biopharma, Takeda, Tesaro/GSK, Toray Industries, VBL Therapeutics, and Xencor; consulting fees from AstraZeneca, BioNTech, DualityBio, Eisai, ImmunoGen/AbbVie, Imunon, Imvax, Incyte, InxMed, Karyopharm Therapeutics, Mersana Therapeutics, Natera, Onconova Therapeutics/Traws Pharma, OnCusp Therapeutics, R Pharm, Regeneron, Seagen/Pfizer, Sutro Biopharma, and Tesaro/GSK; and participation on a data safety monitoring or advisory board for AstraZeneca, BeiGene, BioNTech, Daiichi Sankyo, I-Mab Biopharma, Imunon, ImmunoGen/AbbVie, Imvax, InxMed, LOXO Oncology/Lilly, Mersana Therapeutics, MSD, Nuvation Bio, Onconova Therapeutics/Traws Pharma, Sutro Biopharma, Tesaro/GSK, and Toray Industries.

References

1. Oaknin A, Sabatier R, Pothuri B, et al. Six-year survival outcomes with dostarlimab monotherapy in patients with dMMR/MSI-H endometrial cancer in the GARNET trial. Presented at: 2026 ESMO Gynaecological Cancers Annual Congress; June 17-19, 2026; Copenhagen, Denmark.
2. FDA approves immunotherapy for endometrial cancer with specific biomarker. News release. FDA. April 22, 2020. Accessed June 20, 2026. https://www.prnewswire.com/news-releases/fda-approves-immunotherapy-for-endometrial-cancer-with-specific-biomarker-301275272.html
3. Hollasch M. Dostarlimab fills unmet need for patients with dMMR advanced endometrial cancer: Q&A with Lucy Gilbert, MD, MSc. OncLive.com. March 20, 2023. Accessed June 20, 2026. https://www.onclive.com/view/dostarlimab-fills-unmet-need-for-patients-with-dmmr-advanced-endometrial-cancer
4. FDA Approval Insights: Dostarlimab in dMMR advanced endometrial cancer: OncLive On Air. OncLive.com. April 13, 2023. Accessed June 20, 2026. https://www.onclive.com/view/fda-approval-insights-dostarlimab-in-dmmr-advanced-endometrial-cancer
5. Oaknin A, Pothuri B, Gilbert L, et al. Safety, efficacy, and biomarker analyses of dostarlimab in patients with endometrial cancer: interim results of the phase I GARNET study. Clin Cancer Res. 2023;29(22):4564-4574. doi:10.1158/1078-0432.CCR-22-3915
6. Oaknin A, Gilbert L, Tinker AV, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET—a phase I, single-arm study. J Immunother Cancer. 2022;10(1):e003777. doi:10.1136/jitc-2021-003777