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ProfoundBio's Rinatabart Sesutecan Granted FDA Fast Track Designation for Ovarian Cancer


Rinatabart sesutecan (Rina-S; PRO1184) is under evaluation for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

Image credit: Lars Neumann | stock.adobe.com

Image credit: Lars Neumann | stock.adobe.com

The FDA has granted Fast Track designation to ProfoundBio’s rinatabart sesutecan (Rina-S; PRO1184) to treat patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.1 The novel folate receptor alpha (FRα)–targeted antibody-drug conjugate (ADC) is comprised of an FRα-directed antibody linked to sesutecan, which is an investigational, cleavable hydrophilic linker, and the topoisomerase 1 inhibitor payload exatecan.

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

Sesutecan was developed to mask the hydrophobic nature of conjugated exatecan on the ADC, which facilitates a drug-to-antibody ratio of eight, to efficiently deliver the drug to tumors while maintaining the favorable physicochemical and pharmacokinetic (PK) properties of the ADC. Data from the dose-expansion portion (part A) of the multicenter, open-label Phase I/II PRO1184-001 trial (NCT05579366) showed early signs of antitumor activity and tolerability in patients with heavily pretreated ovarian and endometrial cancer unselected for FRα expression.

These safety and efficacy data demonstrated that Rina-S was well-tolerated across dosing ranges from 60 mg/m2 to 120 mg/m2. Further, the 140-mg/m2 dose remains under investigation as a potential maximum-tolerated dose (MTD).2 

Among 21 efficacy-evaluable patients with ovarian and endometrial cancer, one patient had an unconfirmed complete response, seven experienced partial responses, and nine achieved stable disease. The responses were observed across FRα expression and dose levels from 60 mg/m2 to 140 mg/m2. Responses were found to deepen over time for most patients in the trial.

The PRO1184-001 trial included a dose-escalation (part A) and dose-expansion (part B) portion. The study analyzed the safety, tolerability, pharmacokinetics, and antitumor activity of the drug in patients multiple locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non–small cell lung cancer, and mesothelioma.

Enrollment criteria included being 18 years of age and older with histologically or cytologically confirmed metastatic or unresectable solid tumors; previous treatment with all therapies found to provide a clinical benefit; the willingness and ability to provide tumor samples; an ECOG performance status 0 or 1; and measurable disease per RECIST v1.1 criteria.

Exclusion criteria from part A included a history of another malignancy within three years; known active metastases in the central nervous system; and HIV infections or active hepatitis B or C. Patients in part B were required to have evidence of FRα expression in tumor cells.3

The primary endpoints of the study include identification of the MTD and recommended Phase II dose (RP2D) of Rina-S and incidence of dose-limiting toxicities, safety, and tolerability, with key secondary endpoints that include antitumor activity and PK data.

Patients in part A were intravenously administered single agent Rina-S at five ascending doses that ranged from 60 mg/m2 to 180 mg/m2 on day one of a 21-day cycle.2 Patients in part B were administered Rina-S at the RP2D according to a comprehensive analysis of data for safety, tolerability, clinical PK, pharmacodynamics and activity from part A in up to four different cohorts with no more than 20 patients per cohort.3

Investigators will continue to administer Rina-S until patients experience disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the sponsor, pregnancy, or death. The trial has an estimated completion date of September 25, 2025.2,3


  1. ProfoundBio announces rinatabart sesutecan FDA fast track designation for patients with advanced ovarian cancer. News release. ProfoundBio. January5, 2024. Accessed January 8, 2024. https://profoundbio.com/News-Detail?article_id=52
  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). ClinicalTrials.gov. Updated September 11, 2023. Accessed January 8, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05579366
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