Researchers presented new research studies during the 2025 Society of Gynecologic Oncology (SGO) Annual Meeting, held March 14-17. The Dana-Farber led studies exemplified innovative clinical research for the improvement of treatment for gynecologic cancers.
Panagiotis Konstantinopoulos, MD, PhD, the Velma Eisenson Chair for Clinical and Translational Research in Gynecologic Oncology, presented findings from the RESOLVE study of a phase 2 clinical trial showing that treatment with metformin, letrozole, and abemaciclib for recurrent estrogen receptor-positive endometrial cancer is safe and appears to induce deeper and more durable responses than letrozole and abemaciclib alone.
The team initiated the trial based on preclinical research suggesting synergy between the three drugs, which together inhibit the estrogen receptor, CDK4/6, and PI3K pathways. All 25 patients in the trial received the three medicines. At a median of 17 months of follow-up, three patients had a complete response, five a partial response, and sixteen had stable disease. Based on next-generation sequencing of tumors, the team found that all the complete and partial responses were observed in patients with no specific molecular profile (NSMP) endometrial cancers without RB1 or CCNE1 mutations, suggesting this patient group will derive the most benefit from this combination.
"Addition of metformin to hormonal therapy and CDK4/6 inhibition with abemaciclib demonstrated encouraging and durable evidence of activity in NSMP endometrial cancers providing support for simultaneous inhibition of ER, CDK4/6 and PI3K pathways in this setting," said Konstantinopoulos.
Elizabeth K. Lee, MD presented results from a phase 1/2 clinical trial reporting that Rinatabart sesutecan (Rina-S), an investigational, novel antibody-drug conjugate directed at folate receptor alpha (FRα), showed encouraging preliminary antitumor activity as a single agent in a dose expansion cohort of patients with advanced ovarian cancer.
The open-label, multicenter phase 1/2 study tested Rina-S in a cohort of 42 patients with heavily treated advanced ovarian cancer. Patients received one of two doses of Rina-S (100 mg/m2 or 120 mg/m2) every three weeks. After a median of 24 weeks of follow-up, 22.7% of patients taking the lower dose and 55.6% of patients taking the higher dose had confirmed objective responses, with 2 complete responses in the higher dose group. Side effects included low blood counts and gastrointestinal distress. The results support further testing of single-agent Rina-S at 120mg/m2; enrollment of patients with platinum resistant ovarian cancer is ongoing in a phase 2 study (RAINFOL-OV1) and in a randomized phase 3 study (RAINFOL-OV2/GOG-3107, NCT06619236).
"Rina-S, a novel FRa-directed antibody-drug conjugate, demonstrated encouraging activity in patients with ovarian cancer, across FRa expression levels," said Lee. "These findings support the further study of Rina-S in ovarian cancer."