FDA Grants Fast Track Status to Rinatabart Sesutecan for FRα-Expressing Ovarian Cancer

The FDA has granted fast track designation to rinatabart sesutecan for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.



The FDA has granted fast track designation to the novel folate receptor alpha (FRα)–targeted antibody-drug conjugate (ADC) rinatabart sesutecan (Rina-S; PRO1184) for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.1

Rina-S consists of an FRα-directed antibody linked to sesutecan, a novel, cleavable hydrophilic linker developed by ProfoundBio, and the topoisomerase 1 inhibitor payload, exatecan. Sesutecan was specifically designed to conceal the hydrophobic nature of conjugated exatecan on the ADC. This design facilitates a drug-to-antibody ratio of 8, which should ensure efficient delivery of the exatecan payload to tumors while preserving the favorable physicochemical and pharmacokinetic (PK) properties of the ADC.

The agent demonstrated early signals of antitumor activity and tolerability among patients with heavily pretreated ovarian and endometrial cancer who were unselected for FRα expression, as seen in the dose-expansion portion (part A) of the phase 1/2 PRO1184-001 trial (NCT05579366).1

Preliminary safety and efficacy data were reported during the 2023 SITC Annual Meeting and showed that Rina-S was well tolerated at doses ranging from 60 mg/m2 to 120 mg/m2, with the 140-mg/m2 dose still under evaluation as a potential maximum tolerated dose (MTD).2 Of the 21 efficacy-evaluable patients with ovarian and endometrial cancers, there was 1 unconfirmed complete response and 7 partial responses; 9 patients achieved stable disease. Responses occurred across FRα expression levels and dose levels ranging from 60 mg/m2 to 140 mg/m2, with responses deepening over time for most patients.

“Our receipt of fast track designation from the FDA underscores our belief in the tremendous promise of Rina-S as a potential best-in-class FRα ADC to address the significant need for improved treatment options for advanced ovarian cancer,” Naomi Hunder, Chief Medical Officer of ProfoundBio, stated in a news release.1

The multicenter, open-label trial was designed to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of PRO1184 in multiple locally advanced and/or metastatic solid tumors including epithelial ovarian cancer, endometrial cancer, breast cancer, non–small cell lung cancer, and mesothelioma. The study consisted of dose-escalation (part A) and dose-expansion (part B) phases.

Patients aged 18 years and older with histologically or cytologically confirmed metastatic or unresectable solid tumors were enrolled onto the study.2,3 Other key inclusion criteria include prior exposure to all therapies known to confer clinical benefit, willingness and ability to provide tumor samples, an ECOG performance status 0 or 1, and measurable disease per RECIST v1.1 criteria. Patients were excluded from part A of the study if they had a history of another malignancy within 3 years, known active central nervous system metastases, and human immunodeficiency virus infections or active hepatitis B or C. Notably, patients in part B also need to have evidence of FRα expression in tumor cells.3

In part A, patients were intravenously administered Rina-S as a single agent at 5 ascending doses ranging from 60 mg/m2 to 180 mg/m2 on day 1 of a 21-day cycle.2 In part B, patients will receive Rina-S at the recommended phase 2 dose (RP2D) according to a comprehensive analysis of safety, tolerability, clinical PK, pharmacodynamic and activity data from part A in a maximum of 4 different cohorts with no more than 20 patients per cohort.3

Patients will continue to receive Rina-S until disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the sponsor, pregnancy, or death.2,3

The study’s primary end points include identification of the MTD and RP2D of Rina-S, as well as the incidence of dose-limiting toxicities, safety, and tolerability. Key secondary end points include antitumor activity and PK data.

As of September 27, 2023, 36 patients have been treated with Rina-S across 6 sites in the United States and 1 in China. Enrollment in the dose-expansion phase of the trial is currently ongoing at multiple sites.The study has an estimated completion date of September 25, 2025.

“FRα is a highly prevalent antigen in ovarian cancer and Rina-S has shown encouraging antitumor activity and tolerability in our phase 1 dose-escalation study in ovarian and endometrial cancer patients across the full spectrum of FRα expression,” Hunder added in the news release. “We look forward to working closely with the FDA as we progress further clinical development and registrational studies for Rina-S.”


  1. ProfoundBio announces rinatabart sesutecan FDA fast track designation for patients with advanced ovarian cancer. News release. ProfoundBio. January5, 2024. Accessed January 8, 2024.
  2. Call J, Anderson I, Winer I, et al. A phase 1/2 study of rinatabart sesutecan (PRO1184), a novel folate receptor alpha-directed antibody-drug conjugate, in patients with locally advanced and/or metastatic solid tumors. Journal for ImmunoTherapy of Cancer.2023;11. doi: 10.1136/jitc-2023-SITC2023.0708
  3. PRO1184 for advanced solid tumors (PRO1184-001). Updated September 11, 2023. Accessed January 8, 2024.

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