Ana Oaknin, MD, principal investigator, Gynecological Malignancies Group, Vall d’Hebron Institute of Oncology, head of Gynecologic Tumors Unit, senior medical oncologist and attending physician, Medical Oncology Department, Vall d’Hebron University Hospital, discusses the rationale for the phase I/II GARNET trial in endometrial cancer.

Patients with endometrial cancer can have tumors that are microsatellite stable (MSS) or microsatellite instability—high (MSI-H). However, the anti–PD-1 therapy pembrolizumab (Keytruda) is FDA approved for patients with MSI-H solid tumors, not MSS solid tumors. As such, the GARNET trial was designed to evaluate the efficacy of anti–PD-1 agents specifically in all-comers with endometrial cancer, says Oaknin.

Although MSI-H tumors have shown a particular amenability to immunotherapy, data suggest that both MSS and MSI-H respond to anti—PD-1 therapy. For example, in a phase II trial (NCT02501096) that evaluated the combination of pembrolizumab and lenvatinib (Lenvima), investigators reported responses in both patient populations, irrespective of MSI status.

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Dr. Oaknin on the Rationale for the GARNET Trial in Endometrial Cancer

Ana Oaknin, MD, principal investigator, Gynecological Malignancies Group, Vall d’Hebron Institute of Oncology, head of Gynecologic Tumors Unit, senior medical oncologist and attending physician, Medical Oncology Department, Vall d’Hebron University Hospital, discusses the safety profile of dostarlimab (TSR-042) in patients with endometrial cancer.

Dostarlimab is well tolerated among patients, says Oaknin. However, in 70% of patients enrolled in the phase I/II GARNET trial, investigators did observe treatment-related adverse events (AEs). In terms of immune-related AEs, less than 6% of patients developed grade 3 or 4 events. Additionally, no deaths were reported as a result of the drug, she adds.

Regarding the agent’s mechanism of action, dostarlimab is an investigational, humanized antibody that prevents the interaction between PD-1 and PD-L1. Moreover, it stimulates the immune system to fight a patient’s tumor cells and has shown a strong signal of activity in patients with recurrent or advanced microsatellite instability—high and microsatellite stable endometrial cancer.

Dr. Oaknin on the Safety Profile of Dostarlimab in Endometrial Cancer

Ana Oaknin, MD, principal investigator, Vall d’Hebron Institute of Oncology, Gynecological Malignancies Group, head of Gynecologic Tumors Unit, Medical Oncology Department, Vall d’Hebron University Hospital, discusses findings of the GARNET study in endometrial cancer.

The phase I/II GARNET trial is the largest study analyzing an anti—PD-1 monoclonal antibody in patients with advanced endometrial cancer. In the study, dostarlimab (TSR-042) demonstrated a clinically meaningful overall response rate (ORR) in all patients irrespective of microsatellite instability (MSI) status. ORR in the overall population was approximately 30%. In the microsatellite–stable population, ORR was 20.3%. In the MSI–high population, ORR was 48.8%, Oaknin says.

The most promising aspect of this study was the duration of response, she adds. Although median duration of response has not been reached, 89% of patients remained on treatment for more than 6 months and 49% of patients remained on treatment for more than 1 year. This is important, Oaknin concludes, because patients with advanced endometrial cancer remain a significant unmet need.

Dr. Oaknin Discusses Findings of the GARNET Study in Endometrial Cancer

Ana Oaknin, MD, principal investigator, Vall d’Hebron Institute of Oncology, Gynecological Malignancies Group, head of Gynecologic Tumors Unit, Medical Oncology Department, Vall d’Hebron University Hospital, discusses the phase I/II GARNET trial in patients with endometrial cancer.

In the phase I/II trial, investigators examined the anti—PD-1 monoclonal antibody, dostarlimab (TSR-042), in patients with solid tumors. Results from the cohort of patients with recurrent or advanced microsatellite instability-high (MSI-H) and microsatellite stable (MSS) endometrial cancer were presented at the 2019 Annual SGO Meeting, says Oaknin.

To be eligible for enrollment, patients had to have recurrent or advanced endometrial cancer and have already progressed on or after a platinum-based chemotherapy. Approximately half of patients had received ≥2 prior lines of chemotherapy, representing a heavily pretreated patient population with a historically poor prognosis, says Oaknin. Data showed that patients treated with dostarlimab had an objective response rate of almost 30% . Moreover, these responses were durable—irrespective of MSI-H or MSS status.

Ana Oaknin, MD

Articles

Dr. Oaknin on the Rationale for the GARNET Trial in Endometrial Cancer

Dr. Oaknin on the Safety Profile of Dostarlimab in Endometrial Cancer

Dr. Oaknin Discusses Findings of the GARNET Study in Endometrial Cancer

Dr. Oaknin on the GARNET Study in Endometrial Cancer