Rinatabart Sesutecan Elicits Responses in PROC Regardless of FRα Expression

Rinatabart sesutecan (Rina-S), an investigational folate receptor alpha (FRα)–directed, topoisomerase I (TOPO1)–inhibitor antibody-drug conjugate (ADC), yielded durable, clinically meaningful responses in patients with platinum-resistant ovarian cancer (PROC), according to results from part C of the phase 1/2 RAINFOL-01 trial (NCT05579366) presented in a late-breaking oral session at the 2026 International Gynecologic Cancer Society (IGCS) Congress in Montreal, Canada, per a news release from the developer, Genmab.¹

What efficacy results were reported from RAINFOL-01 part C?

Among 109 patients, the confirmed objective response rate (ORR) was 45.9% (95% CI, 36.3%-55.7%), including 5 complete responses. The median duration of response (DOR) was 12.1 months (95% CI, 6.5-15.4), with 51% of responders remaining in response at 1 year. The median progression-free survival (PFS) was 9.5 months (95% CI, 7.6-11.3), and median follow-up exceeded 1 year. Treatment also demonstrated antitumor activity regardless of FRα expression, including in patients with low FRα expression and in non-expressors, as well as regardless of prior treatment with mirvetuximab soravtansine-gynx (Elahere).

“The antitumor activity and durability observed with Rina-S in this heavily pretreated population are encouraging and suggest the potential to meaningfully impact outcomes for patients [with] a particularly challenging stage of disease,” stated Elizabeth K. Lee, MD, study investigator and a medical oncologist in the gynecologic oncology program at Dana-Farber Cancer Institute, in the press release.¹

Part C followed earlier results from RAINFOL-01, in which the randomized dose-expansion cohort of part B showed a confirmed ORR of 55.6% (95% CI, 30.8%-78.5%) with a dose of 120 mg/m² vs 22.7% (95% CI, 7.8%-45.4%) with 100 mg/m², as presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.²

What safety findings were reported?

The most common treatment-emergent adverse events (TEAEs) were fatigue (57.8%) and low-grade gastrointestinal events, including nausea (67.9%), vomiting (36.7%), constipation (26.6%), decreased appetite (23.9%), and abdominal pain (18.3%). Among the most frequent hematologic TEAEs were anemia (57.8%), neutropenia (57.8%), decreased platelet counts (34.9%), and thrombocytopenia (34.9%).

Serious adverse events were reported in approximately one-third of participants, and 5.5% discontinued treatment because of TEAEs. No safety signals for ocular toxicity, peripheral neuropathy, interstitial lung disease, or stomatitis were observed.

How was part C of RAINFOL-01 designed?

Part C evaluated Rina-S at 120 mg/m² every 3 weeks as monotherapy in patients with platinum-resistant high-grade serous ovarian, primary peritoneal, or fallopian tube cancer. Eligible patients had received 1 to 3 prior lines of therapy, though those who received mirvetuximab as their last prior therapy could have had up to 4 prior lines. More than half of patients (53%) had received 3 or 4 prior lines, and all patients had received prior bevacizumab and a taxane. A total of 49.5% had received a PARP inhibitor, and 33% had received prior mirvetuximab soravtansine-gynx, a different FRα-directed ADC approved by the FDA for FRα-positive PROC.³

RAINFOL-01 is an open-label, multicenter phase 1/2 study evaluating Rina-S every 3 weeks at various doses in selected solid tumors, including tumors across a range of FRα expression levels.¹

What is next for rinatabart sesutecan?

Rina-S is composed of a human monoclonal antibody directed at FRα, a hydrophilic protease-cleavable linker, and exatecan, a TOPO1 inhibitor payload. The development program includes 4 phase 3 trials: RAINFOL-02 in PROC (NCT06619236), RAINFOL-03 in recurrent or progressive endometrial cancer (NCT07166094), RAINFOL-04 in maintenance therapy for platinum-sensitive ovarian cancer (NCT07225270), and RAINFOL-07 in second-line platinum-sensitive ovarian cancer (NCT07564141). Phase 2 trials are also evaluating Rina-S in non–small cell lung cancer (RAINFOL-05; NCT07288177) and advanced gastrointestinal cancers (RAINFOL-09; NCT07539311).

“The late-breaking results presented today add an important layer of evidence to the growing clinical experience with Rina-S in patients with [PROC],” stated Tahamtan Ahmadi, MD, PhD, executive vice president, chief medical officer, and head of experimental medicines at Genmab, in the press release.¹

References

1. Genmab announces rinatabart sesutecan (Rina-S®) phase 2 RAINFOL™-01 results demonstrated durable and clinically meaningful responses in patients with platinum-resistant ovarian cancer. News release. Genmab A/S. October 3, 2026. Accessed October 5, 2026. https://tinyurl.com/43ta993r
2. Lee EK, Yeku O, Winer I, et al. Rinatabart sesutecan (Rina-S®) for patients with advanced ovarian cancer: results from dose expansion cohort B1 of a phase 1/2 study. Presented at: 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 809034.
3. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. News release. FDA. March 22, 2024. Accessed October 5, 2026. https://tinyurl.com/2apx6e5s