Genmab has reported encouraging findings from the Phase 2 RAINFOL-01 trial of rinatabart sesutecan (Rina-S®), an experimental folate receptor-alpha (FRα)-targeted, TOPO1 antibody-drug combination (ADC). Data from the B1 cohort of the trial showed encouraging antitumor efficacy in highly pre-treated patients with advanced ovarian cancer (OC) independent of FRα expression levels.
Rina-S 120 mg/m2 Q3W showed a verified objective response rate (ORR) of 55.6% and a disease control rate (DCR) of 88.9% at a median on-study follow-up of 48 weeks. Especially, the median duration of response (mDOR) was not attained, hence stressing Rina-S’s possible relevance for patients with platinum-resistant ovarian cancer (PROC). The 2025 Society of Gynaecologic Oncology Annual Meeting on Women’s Cancer® (SGO) in Seattle featured these results.
“The antitumor activity observed in the dose expansion cohort continues to demonstrate the potential for a much-needed treatment option for patients with PROC, who have historically had poor prognosis. I am hopeful that further exploration of Rina-S will lead to advancements in the treatment landscape.” said Elizabeth Lee, M.D., a medical oncologist in the gynecologic oncology program at Dana-Farber.
Promising Data from Phase 2 RAINFOL-01 Study
The B1 group comprised advanced OC patients with epithelial ovarian cancer, primary peritoneal cancer, and fallopian tube cancer. Patients were randomised 1:1 into two dosage cohorts: 100 mg/m2 and 120 mg/m2 Q3W. Of 18 evaluable patients given Rina-S 120 mg/m2, 4 (2 verified, 2 unverified) had whole responses; 8 (44.4%) had verified partial responses. Most apparent by week six of the trial, responses were seen early.
By contrast, the lower 100 mg/m2 dosage group revealed a verified ORR of 22.7% and a DCR of 86.4% over a median follow-up of 46 weeks. These findings guided the choice of the 120 mg/m2 dose for more investigation in RAINFOL-02 continuous Phase 2 and Phase 3 studies.
Tolerability and Safety Data
Common treatment-emergent adverse events (TEAEs) include anaemia, nausea, neutropenia, exhaustion, and thrombocytopenia helped the trial to also provide consistent safety statistics. Notably, no new safety signals were found, dose reductions were uncommon, and therapy discontinuations were uncommon, emphasising Rina-S’s reasonable safety profile.
“The updated results reinforce the potential of Rina-S and further validate our development approach in advanced ovarian cancer,” said Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer of Genmab. “We are excited to keep moving forward with the ongoing Phase 3 trial, to evaluate the potential of Rina-S as a treatment option for patients facing this challenging disease.”
A Pressing Global Health Challenge: Ovarian Cancer
With more than 320,000 new cases identified each year, ovarian cancer continues to be a major worldwide health concern. Often discovered at an advanced stage owing to modest signs such abdominal bloating and pelvic pain, ovarian cancer ranks ninth among most prevalent malignancy among women. A difficult subtype of the disease known as platinum-resistant ovarian cancer has few therapeutic choices and a high recurrence rate of 70-90% after initial therapy. Ovarian cancer’s five-year survival rate is still low, usually between 30 and 50%, which highlights the pressing need for creative therapies.
Regarding the RAINFOL-01 Trial
A multi-part, open-label Phase 1/2 trial evaluating the safety and effectiveness of Rina-S in solid tumours recognised for FRα expression, RAINFOL-01 (NCT05579366). Dose-escalation groups, tumor-specific dose-expansion groups, and combination therapy groups are all part of the study. Early results from the trial had been previously shown at the 2024 European Society of Medical Oncology Congress (ESMO).
Including bevacizumab, PARP inhibitors, and mirvetuximab soravtansin, B1 cohort patients had a median of three prior lines of treatment. The first findings of the cohort contribute to the mounting data suggesting Rina-S’s possible function in treating PROC.
Looking Forward
The promising results of Rina-S’s continuous studies represent a major advancement in creating successful treatments for advanced ovarian cancer. Genmab stays concentrated on moving the ongoing Phase 3 RAINFOL-02 trial forward, which seeks to validate Rina-S’s possibility as a unique therapy choice for PROC patients.
Although Rina-s’s safety and effectiveness for its investigational uses are still being determined, the revised data provides fresh optimism for better results in a difficult and previously neglected patient group.
