Dr Lee on the Future Development of Rina-S in FRα+ Platinum-Resistant Ovarian Cancer

“With these very encouraging results [from RAINFOL-01] we are hopeful to continue to advance the treatment landscape for patients with platinum-resistant ovarian cancer as a whole.”

Elizabeth Lee, MD, a medical oncologist at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discussed next steps with the novel folate receptor alpha (FRα)–directed antibody-drug conjugate rinatabart sesutecan (Rina-S; PRO1184) for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

Findings from cohort B1 of the phase 1/2 RAINFOL-01 trial (NCT05579366) presented during the 

2025 SGO Annual Meeting on Women’s Cancer

 showed that, at a median follow-up of 46 months, patients who received Rina-S at 100 mg/m

 every 3 weeks (n = 22) achieved a confirmed overall response rate (ORR) of 22.7% (95% CI, 7.8%-45.4%), including 1 patient with a complete response, and a disease control rate of 86.4% (95% CI, 65.1%-97.1%). Notably, the median duration of response was not reached (NR; 95% CI, 16.3-NR).

In terms of safety, common treatment-emergent adverse effects included anemia, nausea, neutropenia, leukopenia, fatigue, thrombocytopenia, vomiting, diarrhea, alopecia, and hypokalemia. No new safety signals were reported, and dose reductions and therapy discontinuations were not common.

Investigators are hopeful that data from RAINFOL-01 will continue to advance the treatment paradigm in platinum-resistant ovarian cancer, Lee said. She noted that the dose-expansion data presented during the 2025 SGO Annual Meeting were in a limited subset of patients. Part C of RAINFOL-01, which will enroll approximately 100 patients with advanced ovarian cancer, will provide additional data, she added. However, based on the encouraging findings from RAINFOL-01, investigators have initiated the phase randomized phase 3 RAINFOL-02 trial (NCT06619236) comparing Rina-S with investigator’s choice of chemotherapy, she concluded.

RAINFOL-02 is an open-label trial that is enrolling patients irrespective of FRα levels with platinum-resistant ovarian cancer. Patients are required to have received 1 to 4 prior lines of therapy. The primary end point is progression-free survival (PFS). Secondary end points include overall survival, ORR, DOR, time to second PFS, quality of life measures, and safety.

Videos

Elizabeth Lee, MD, discusses the future of Rina-S in FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

Dr Lee on the Mechanism of Action of Rina-S in FRα+ Platinum-Resistant Ovarian Cancer

"There’s a real need to try to expand [the use of] FRα-targeted therapies to more of our patients with ovarian cancer [who have differing levels of FRα expression]. Rina-S does carry a different payload than mirvetuximab soravtansine—exatecan, which is a topoisomerase I inhibitor payload."

Elizabeth Lee, MD, a medical oncologist at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discusses the mechanism of action of rinatabart sesutecan (Rina-S; PRO1184) in patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

Rina-S is a novel folate receptor alpha (FRα)–directed antibody-drug conjugate. FRα is a validated therapeutic target in ovarian cancer and is also the target of mirvetuximab soravtansine (Elahere), an FDA-approved agent in this setting, Lee noted. However, given the heterogeneity of FRα expression in patients with ovarian cancer, there remains a clinical need to expand the applicability of FRα-targeted therapies to a broader patient population, Lee explained.

This is particularly relevant in the context of platinum-resistant ovarian cancer, where treatment options remain limited, Lee added. Rina-S uses a different cytotoxic payload than mirvetuximab soravtansine—exatecan, a topoisomerase I inhibitor—which may contribute to its activity across varying levels of FRα expression, Lee commented.

The efficacy and safety of Rina-S monotherapy in patients with advanced ovarian cancer were evaluated in the phase 1/2 RAINFOL-01 trial (NCT05579366), Lee said. 

Updated findings from dose expansion cohort B1

, demonstrated clinical activity with Rina-S in heavily pretreated patients with platinum-resistant ovarian cancer. At a median follow-up of 46.4 months (range, 6.6-65.3) among evaluable patients in the 100 mg/m

 cohort (n = 22) and 48.1 months (range, 10.9-65.9) among evaluable patients in the 120 mg/m

 cohort (n = 18), the confirmed objective response rates were 22.7% (95% CI, 7.8%-45.4%) and 55.6% (95% CI, 30.8%-78.5%), respectively.

Notably, early and durable responses were observed in patients who received the 120-mg/m

 dose regardless of their level of FRα expression. The median duration of response was not reached (NR; 95% CI, 16.3 months-NR) in the 100 mg/m

 cohort and NR (95% CI, 40.14 months-NR) in the 120 mg/m

Elizabeth Lee, MD, discusses the need for FRα-targeted therapies with differing payloads for patients with platinum-resistant ovarian cancer.

 Dr Lee on the Safety Profile of Rinatabart Sesutecan in FRα+ Platinum-Resistant Ovarian Cancer

“There were…a total of 4 CRs, 2 of which are pending confirmation. With the longer duration of follow-up… the median DOR has still not yet been reached. We’re very, very encouraged by the findings so far.”

Elizabeth Lee, MD, a gynecologic oncologist and the gynecologic oncology program's liaison to the Center for Cancer Therapeutics Innovation at Dana-Farber Cancer Institute, discusses results from the dose-expansion cohort B1 of 

 (NCT05579366) evaluating the novel folate receptor alpha (FRα)–targeted antibody-drug conjugate rinatabart sesutecan (Rina-S; PRO1184) for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

 demonstrated clinical activity and tolerability with Rina-S across 2 dose cohorts in patients with advanced gynecologic malignancies, Lee began. At a median follow-up of 46.4 months (range, 6.6–65.3) for the 100 mg/m² cohort (n = 22) and 48.1 months (range, 10.9–65.9) for the 120 mg/m² cohort (n = 20), the confirmed objective response rates (ORRs) were 22.7% (95% CI, 7.8%–45.4%) and 55.6% (95% CI, 30.8%–78.5%), respectively. Across both cohorts, 4 CRs were observed, 2 of which were pending confirmation at the time of analysis, Lee noted. The disease control rates were 86.4% (95% CI, 65.1%–97.1%) and 88.9% (95% CI, 65.3%–98.6%) in the respective cohorts.

Notably, Rina-administered at 120 mg/m² elicited early, deep, and durable responses at the 120 mg/m² dose regardless of FRα expression levels. The median duration of response (DOR) was not reached (NR; 95% CI, 16.3 months–NR) in the 100 mg/m² group and NR (95% CI, 40.14 months–NR) in the 120 mg/m² group.

Treatment was generally well tolerated, with manageable treatment-emergent adverse effects and no new safety signals. Across cohorts, 4 CRs were observed, 2 of which were pending confirmation at the time of analysis. The prolonged follow-up and sustained DOR support continued investigation of Rina-S in this setting, Lee concluded.

Elizabeth Lee, MD, discusses the efficacy of rinatabart sesutecan in patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

Elizabeth Lee, MD

Articles

Dr Lee on the Future Development of Rina-S in FRα+ Platinum-Resistant Ovarian Cancer

Dr Lee on the Mechanism of Action of Rina-S in FRα+ Platinum-Resistant Ovarian Cancer

Dr Lee on the Antitumor Activity of Rinatabart Sesutecan in FRα+ Platinum-Resistant Ovarian Cancer