Dr Mathews on Updated Data From the RAINFOL-01 Trial in Advanced Ovarian Cancer

“Similar to the dose-optimization [cohort of patients with ovarian cancer], there was no interstitial lung disease, no neuropathy, and no ocular toxicity. That wasn’t a surprise, but very reassuring and really a great signal for patients in terms of tolerability.”

Cara A. Mathews, MD, associate professor of obstetrics and gynecology at Brown University Health and Women & Infants Hospital, discussed updated findings from cohort D2 of the phase 1/2 RAINFOL-01 trial (NCT05579366) in advanced ovarian cancer.

In cohort D2 of the study, investigators evaluated the safety and tolerability of rinatabart sesutecan (Rina-S) plus bevacizumab (Avastin) in a heterogeneous population of patients with recurrent ovarian cancer. Approximately two-thirds of enrolled patients had platinum-resistant disease, with the remainder having platinum-sensitive or platinum-refractory disease, Mathews explained. The cohort also allowed multiple histologic subtypes, including high-grade serous, endometrioid, and clear cell carcinomas arising from ovarian, primary peritoneal, and fallopian tube origins. Notably, no minimum FOLR1 expression threshold was required for eligibility although FOLR1 status was assessed retrospectively.

From a tolerability standpoint, the regimen demonstrated a reassuring profile, Mathews said. Consistent with findings from the dose-optimization ovarian cohort, no interstitial lung disease, neuropathy, or ocular toxicity was observed. Approximately half of patients experienced a grade 3 or 4 adverse effect, with cytopenias comprising most of those events––specifically anemia, neutropenia, and thrombocytopenia. These hematologic toxicities were considered clinically manageable with supportive care measures, Mathews added. Grade 1 or 2 nausea was reported in approximately 80% of patients, underscoring the importance of proactive antiemetic strategies when administering antibody-drug conjugates (ADCs) in this setting, Mathews noted.

Investigators also examined whether the addition of bevacizumab to the regimen introduced new safety signals. No additive toxicity was identified; the safety profile of the combination was consistent with what was anticipated from each individual agent. Importantly, bevacizumab did not appear to exacerbate the cytopenia profile associated with Rina-S, with rates remaining comparable with those observed with single-agent Rina-S in prior ovarian cancer cohorts.

Overall, the findings support the tolerability of this regimen across a broadly eligible recurrent ovarian cancer population, providing a foundation for further efficacy evaluation.