FDA Grants FTD to Rinatabart Sesutecan for FRα-Expressing Ovarian Cancer


Rinatabart sesutecan is an antibody drug conjugate that has now received a fast track designation from the FDA for the treatment of FRα-expressing ovarian cancer.

  • Rinatabart sesutecan (PRO1184; Rina-S) is a folate receptor alpha (FRα)-targeted antibody drug conjugate (ADC).

  • The agent is being evaluated in a phase 2 study, PRO1184-001 (NCT05579366), for patients with selected locally advanced and/or metastatic solid tumors.

  • With this fast track designation (FTD), the FDA will facilitate the development and expedited review of Rina-S.

The FDA has granted a FTD to Rina-S for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.1

"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. "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. We look forward to working closely with the FDA as we progress further clinical development and registrational studies for Rina-S."

Rina-S is a FRα targeted ADC under development for the treatment of patients with ovarian and endometrial cancer. The agent is also being developed as a potential novel treatment for other FRα-expressing cancers. Rina-S consists of a FRα-directed antibody that is combined to sesutecan, a proprietary hydrophilic exatecan-based linker-drug, at a homogeneous drug-to-antibody ratio of 8.

The phase 1/2 PRO1184-001 trial is ongoing and assessing the safety, tolerability, pharmacokinetics (PK), and antitumor activity of Rina-S in patients with selected locally advanced and/or metastatic solid tumors. This includes patients with epithelial ovarian cancer, endometrial cancer, breast cancer, non–small cell lung cancer, and mesothelioma.

The study consists of 2 parts: part A, the dose escalation, and part B, the dose expansion. Once enrolled, patients in part A received Rina-S monotherapy in escalating doses. Patients in part B will be treated with the recommended dose determined in part A. 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

Enrollment in the trial is open to patients aged 18 years and older with histologically or cytologically confirmed metastatic or unresectable solid malignancy who have previously received therapies known to confer clinical benefit. Patients must be willing to provide a tumor sample; have an ECOG performance status 0 or 1; have measurable disease per RECIST v1.1; and have adequate hematologic, hepatic, renal, and cardiac function. For part B, patients must also have evidence of FRα expression in tumor cells.

The primary end points of the study include incidence of treatment-emergent adverse events and dose-limiting toxicities. Secondary end points are best overall response, objective response rate, disease control rate, progression-free survival, overall survival, duration of objective response, and PK.

In November 2023, initial results from the dose-escalation portion of the trial were reported. In part A, Rina-S in heavily pretreated patients with ovarian and endometrial cancer unselected for FRα expression elicited encouraging antitumor activity at well tolerated doses.1

Now, patients are currently being enrolled into part B of the study across multiple sites in the United States and China. The dose level for part B will be initiated based on a comprehensive analysis of safety, tolerability, clinical PK, pharmacodynamic, and activity data from part A in up to 4 cohorts. Each cohort plans to include 20 patients and the study has an estimated completion date of September 2025.

ProfoundBio announces rinatabart sesutecan FDA fast track designation for patients with advanced ovarian cancer. News release. ProfoundBio. January 5, 2024. Accessed January 5, 2024. http://tinyurl.com/mv2m48wd
PRO1184 for advanced solid tumors (PRO1184-001). ClinicalTrials.gov. Updated September 11, 2023. Accessed January 5, 2024. https://clinicaltrials.gov/ /NCT05579366
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