The novel PD-1 inhibitor retifanlimab appears to be safe and effective in patients with pretreated, recurrent microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) endometrial cancer, according to according to data presented by Berton-Rigaud et al at the Society for Immunotherapy of Cancer (SITC) 2021 Annual Meeting (Abstract 956).

Results of the phase I POD1UM-101 study showed centrally confirmed objective responses in 43.4% of patients, including 14.5% with a complete response and 28.9% with a partial response. In addition, more than three-quarters of patients with objective response had a duration of response of at least 6 months.

“Retifanlimab was well tolerated and demonstrated encouraging antitumor activity in patients with pretreated recurrent MSI-H or dMMR endometrial cancer, consistent with that achieved with other PD-1 therapies,” said lead study author Dominique Berton-Rigaud, MD, of the Institut de Cancérologie de l'Ouest, Centre René Gauducheau, in Saint-Herblain, France.

As Dr. Berton-Rigaud reported, patients with recurrent or metastatic endometrial cancer have limited treatment options and poor prognosis, with a 5-year survival rate of only 17%. However, approximately 25% of endometrial cancers are MSI-H or dMMR. Tumors characterized by abnormalities in DNA repair are associated with high numbers of neoantigens, said Dr. Berton-Rigaud, making immunotherapy with PD-1 inhibitors an attractive option.

Retifanlimab is an investigational humanized immunoglobulin G4 monoclonal antibody against human PD-1, with safety and preliminary clinical activity representative of the PD-1 inhibitor class. In the ongoing first-in-human POD1UM-101 study, retifanlimab demonstrated acceptable tolerability and durable clinical activity as monotherapy in multiple advanced tumor types, including pretreated endometrial cancer.

Safety and Activity Studied in POD1UM-01

During the SITC 2021 Annual Meeting, Dr. Berton-Rigaud reported safety and clinical activity from the POD1UM-101 study from the full cohort of patients with MSI-H or dMMR recurrent endometrial cancer. Patients enrolled in the study had experienced disease progression during or following up to five prior systemic treatments, but were naive to prior treatment with immune checkpoint inhibitors.

Patients received retifanlimab at 500 mg every 4 weeks for up to 2 years. The study’s primary study endpoint was safety. Confirmed best overall response and duration of response were evaluated by independent central review using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

As of July 6, 2021, 76 patients with centrally confirmed MSI-H (85.5%) or dMMR (14.5%) endometrial cancer had received at least one dose of retifanlimab.

Dr. Berton-Rigaud reported that retifanlimab was well tolerated, with no new safety signals observed.

“Adverse events of special interest, including immune-related adverse events, are consistent with available clinical experience with PD-1 and PD-L1 inhibitors,” said Dr Berton-Riguad, who noted that 14.5% of patients experienced a grade 3 or higher treatment-emergent adverse event.

With a median follow-up of 8.4 months, confirmed responses per RECIST criteria were observed in 33 of 76 patients (43.4%), including 11 complete responses and 22 partial responses, and the disease control rate was 76.3%.

“Among patients with confirmed partial response, 14 out of 22 patients (64%) had over 70% tumor size reduction, and 29 of 33 responders remain on treatment,” said Dr. Berton-Riguad.

Median duration of response has not been reached, and 75.8% of patients had a duration of response of at least 6 months.

“These findings support further clinical investigation of retifanlimab, either alone or [as a] combination therapy, in patients with endometrial cancer,” Dr. Berton-Riguad concluded.

Disclosure: This study was sponsored by Incyte Corporation.