Rinatabart sesutecan (Rina-S) significantly improved progression-free survival (PFS) and overall survival (OS) vs investigator’s-choice chemotherapy in patients with platinum-resistant ovarian cancer, irrespective of folate receptor alpha (FRα) expression, meeting both the primary and key secondary end points of the phase 3 RAINFOL-02 trial (NCT06619236).1
Findings announced by Genmab showed that among all randomly assigned patients in the intention-to-treat population (n = 584), both PFS (HR, 0.29; 95% CI, 0.23-0.37; P < .0001) and OS (HR, 0.43; 95% CI, 0.31-0.59; P < .0001) favored Rina-S. In the primary analysis set, which comprised patients with an FRα expression of at least 75% who had prior treatment with Mirvetuximab soravtansine-gynx (Elahere; n = 492), PFS (HR, 0.33; 95% CI, 0.26-0.42; P < .0001) and OS (HR, 0.44; 95% CI, 0.31-0.63; P < .0001) data also favored Rina-S.
The safety profile of Rina-S was in line with prior experience, and no new safety signals emerged.
Data from RAINFOL-02 will be presented at the future medical meeting and shared with global health authorities.
“Platinum-resistant ovarian cancer remains one of the greatest challenges in gynecologic oncology, with patients often facing a poor prognosis and limited effective treatment options. The phase 3 RAINFOL-02 results set a new benchmark in addressing this urgent unmet need regardless of FRα expression,” Angeles Alvarez Secord, MD, MHSc, a professor of obstetrics and gynecology at Duke Cancer Institute and the Gynecologic Oncology Group lead investigator for RAINFOL-02, stated in a news release. “The 71% reduction in the risk of disease progression and 57% reduction in the risk of death underscore the potential of Rina-S to change clinical practice if approved by offering a therapeutic option for a broad patient population.”
Rina-S is an investigational antibody-drug conjugate (ADC) built on a human monoclonal antibody directed against FRα, which is connected to an exatecan payload—a topoisomerase I inhibitor—through a hydrophilic linker designed to be cleaved by proteases. After the ADC binds FRα on tumor cells and is internalized, the linker is cleaved and exatecan is released, where it blocks topoisomerase I activity, interrupting DNA replication and driving tumor cell death.
In the open-label, multicenter phase 3 RAINFOL-02 study enrolled patients at least 18 years of age with high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer with platinum-resistant disease.2 They needed to have received 1 to 4 previous lines of therapy and to have experienced radiographic progression during or after their most recent regimen. FRα expression level did not factor into enrollment.
All patients had previously received platinum-based chemotherapy. Prior treatment with bevacizumab (Avastin), a PARP inhibitor, or mirvetuximab soravtansine was required in certain circumstances, depending on patient eligibility, regional availability, and exceptions specified in the protocol. Patients were excluded if they had primary platinum-refractory disease or had previously received an ADC carrying a topoisomerase I inhibitor payload.
Patients were randomly assigned 1:1 to receive Rina-S at 120 mg/m2 on day 1 of every 21-day cycle or the investigator’s choice of paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine.2
Investigator-assessed PFS per RECIST 1.1 criteria served as the primary end point. Secondary end points included OS, objective response rate, PFS and ORR by blinded independent central review, duration of response, CA-125 response, time to second progression or death, quality of life, and treatment-emergent adverse effects.
