Rinatabart Sesutecan Shows Durable Responses in Platinum-Resistant Ovarian Cancer

Rinatabart sesutecan (Rina-S) yielded durable, clinically meaningful responses in heavily pretreated patients with platinum-resistant ovarian cancer, according to results from part C of the phase 1/2 RAINFOL-01 trial (NCT05579366) presented in a late-breaking oral session at the International Gynecologic Cancer Society (IGCS) 2026 Congress, in Montreal, Canada.¹

Among 109 treated patients with platinum-resistant ovarian cancer, Rina-S achieved a confirmed objective response rate (ORR) of 45.9% (95% CI, 36.3%-55.7%), including 5 complete responses, with a median duration of response (mDOR) of 12.1 months (95% CI, 6.5-15.4) and 51% of responders remaining in response at 1 year.

“As patients relapse and progress through successive lines of therapy, achieving durable clinical benefit becomes increasingly challenging, yet remains critically important,” Elizabeth K. Lee, MD, study investigator and a medical oncologist in the gynecologic oncology program at Dana-Farber Cancer Institute, stated in a news release. She added that the antitumor activity and durability seen with Rina-S “are encouraging and suggest the potential to meaningfully impact outcomes for patients facing a particularly challenging stage of disease.”

Trial Design and Patient Population

RAINFOL-01 is an open-label, multicenter phase 1/2 study evaluating the safety and efficacy of the antibody-drug conjugate (ADC) Rina-S at various doses across solid tumors spanning a range of FRα expression levels. Initial dose escalation results showed efficacy in heavily pretreated patients with ovarian and endometrial cancer unselected for FRα (folate receptor alpha) expression. In a dose expansion phase 2b cohort, Rina-S at 100 mg/m² resulted in a 50.0% overall response rate in patients with advanced endometrial cancer, leading to an FDA breakthrough designation.²

In the part C cohort, Rina-S was given as monotherapy 120 mg/m² every 3 weeks as monotherapy in patients with platinum-resistant high-grade serous ovarian, primary peritoneal, or fallopian tube cancer.¹ Patients had received 1 to 3 prior lines of therapy. Those who received mirvetuximab soravtansine (Elahere), another FRα-targeted ADC, as their last prior therapy could have received up to 4 prior lines; more than half of patients (53%) had received 3 or 4 prior lines of therapy. All patients had received prior bevacizumab (Avastin) and taxane therapy, 49.5% had received a prior PARP inhibitor, and 33% had received prior mirvetuximab soravtansine. The median follow-up was over 1 year.

Antitumor activity was observed across levels FRα expression, including in patients with low or no FRα expression, and in patients with or without prior treatment with mirvetuximab soravtansine. In addition to the durable responses, the study also demonstrated a median progression-free survival (mPFS) of 9.5 months (95% CI, 7.6-11.3).

Safety Profile

More than half of patients (57.8%) reported fatigue; other treatment-emergent adverse events (TEAEs) were primarily low-grade and included nausea in 67.9%, vomiting in 36.7%, constipation in 26.6%, decreased appetite in 23.9%, and abdominal pain in 18.3%. Hematologic TEAEs included anemia and neutropenia, each in 57.8% of patients, with decreased platelet count and thrombocytopenia each occurring at a 34.9% rate. Approximately one-third of patients experienced a serious adverse event, but only 5.5% discontinued treatment because of AEs. There were no safety signals for ocular toxicity, peripheral neuropathy, interstitial lung disease, or stomatitis.

Next Steps for Rina-S in Ovarian Cancer and Beyond

The global open-label phase 3 RAINFOL-02 trial (NCT06619236) is investigating Rina-S in an estimated 584 patients with platinum-resistant ovarian cancer compared with 1 of 4 chemotherapy agents (paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine) selected as investigator’s choice of therapy.³ Patients must have received prior platinum chemotherapy and bevacizumab, must have received mirvetuximab soravtansine if they are eligible and it is indicated in their region, and must have received a PARP inhibitor if BRCA-positive unless ineligible. Patients may be enrolled regardless of FRα expression. They cannot have previously received an ADC containing a topoisomerase 1 inhibitor.

Other phase 3 trials investigating Rina-S include RAINFOL-03 (NCT07166094) in recurrent or progressive endometrial cancer, RAINFOL-04 (NCT07225270) as platinum-sensitive ovarian cancer (PSOC) maintenance therapy, and RAINFOL-07 (NCT07564141) in second-line PSOC. Phase 2 studies include trials in non–small cell lung cancer (RAINFOL-05; NCT07288177) and advanced gastrointestinal cancers (RAINFOL-09; NCT07539311).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/5jrxppa5

2. Genmab Announces Investigational Rinatabart Sesutecan (Rina-S®) Demonstrates Encouraging Anti-Tumor Activity in Heavily Pretreated Patients with Advanced Endometrial Cancer in Phase 1/2 RAINFOL™-01 Trial. News release. Genmab. June 2, 2025. Accessed October 5, 2026. https://tinyurl.com/3z9y33p5

3. Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer (RAINFOL-02). ClinicalTrials.gov. Updated September 28, 2026. Accessed October 5, 2026. https://clinicaltrials.gov/study/NCT06619236