Genmab’s Rina-S met both survival endpoints in the Phase 3 RAINFOL-02 trial, reducing progression risk by 71% and death risk by 57% in platinum-resistant ovarian cancer.
Written By: Neha Vishwakarma, PharmD
Reviewed By: Pharmacally Editorial Team
Genmab has reported positive topline results from the global Phase 3 RAINFOL-02 trial evaluating rinatabart sesutecan (Rina-S; GEN1184) in patients with platinum-resistant ovarian cancer (PROC). The investigational antibody-drug conjugate (ADC) met its primary endpoint of progression-free survival (PFS) and key secondary endpoint of overall survival (OS), demonstrating statistically significant improvements over investigator’s choice chemotherapy.
In the intention-to-treat (ITT) population of 584 patients, Rina-S reduced the risk of disease progression or death by 71% (HR 0.29; 95% CI, 0.23–0.37; p<0.0001). The treatment also reduced the risk of death by 57% (HR 0.43; 95% CI, 0.31–0.59; p<0.0001).
RAINFOL-02 Demonstrates Survival Benefits Across Analysis Populations
RAINFOL-02 (NCT06619236) is a randomized, open-label, multicenter Phase 3 trial comparing Rina-S with investigator’s choice of paclitaxel, topotecan, pegylated liposomal doxorubicin (PLD), or gemcitabine.
Patients received Rina-S at 120 mg/m² on Day 1 of each three-week treatment cycle or one of the comparator chemotherapy regimens.
The study evaluated efficacy in two populations. The ITT population included all 584 randomized patients regardless of folate receptor alpha (FRα) expression. The primary analysis set (PAS) included 492 patients, excluding certain patients with high FRα expression who had not previously received mirvetuximab.
In the PAS population, Rina-S reduced the risk of disease progression or death by 67% (HR 0.33; 95% CI, 0.26–0.42; p<0.0001). Overall survival also improved significantly, with a 56% reduction in the risk of death (HR 0.44; 95% CI, 0.31–0.63; p<0.0001).
The consistent results across both analysis populations support the potential clinical relevance of Rina-S beyond a strictly FRα-high population. However, detailed efficacy outcomes by FRα expression subgroup remain necessary to establish the extent of benefit across different biomarker levels.
Rina-S Targets FRα With a Topoisomerase I Inhibitor Payload
Rina-S combines a human monoclonal antibody targeting FRα with a protease-cleavable linker and exatecan, a topoisomerase I inhibitor payload.
FRα is expressed in many ovarian tumors and represents an established therapeutic target. Unlike conventional chemotherapy, the ADC approach uses antibody-mediated targeting to deliver a cytotoxic payload to tumor cells, although systemic toxicity remains possible.
Platinum-resistant ovarian cancer presents a substantial clinical challenge because patients experience disease progression despite platinum-based treatment and frequently have limited effective treatment options.
Genmab reported that Rina-S demonstrated a safety profile consistent with previous clinical experience, with no new safety signals or unexpected safety concerns.
However, detailed rates of treatment-related adverse events, severe toxicities, dose reductions, and discontinuations were not disclosed in the topline announcement.
Genmab Plans Regulatory Discussions Following Phase 3 Success
Genmab intends to engage regulatory authorities worldwide to discuss potential next steps for Rina-S. The company also plans to submit the complete findings for presentation at a future medical meeting.
Chief Executive Officer Jan van de Winkel described RAINFOL-02 as the first Phase 3 readout from the Rina-S program, strengthening the company’s confidence in its development across gynecologic cancers.
The broader clinical program includes Phase 3 trials in recurrent or progressive endometrial cancer (RAINFOL-03), platinum-sensitive ovarian cancer maintenance therapy (RAINFOL-04), second-line platinum-sensitive ovarian cancer (RAINFOL-07), and first-line ovarian cancer maintenance therapy (RAINFOL-10).
Additional Phase 2 studies are evaluating Rina-S in non-small cell lung cancer and advanced gastrointestinal cancers.
The simultaneous improvement in PFS and OS represents an important finding in platinum-resistant ovarian cancer, particularly given the trial’s inclusion of patients across FRα expression levels. Nevertheless, median survival outcomes, subgroup analyses, and comprehensive safety data will be essential to assess the magnitude of clinical benefit and inform regulatory review.
Rina-S remains investigational, and its safety and efficacy have not yet been established.
Reference
Genmab Announces Rinatabart Sesutecan (Rina-S®) Demonstrates Statistically Significant Improvement in Progression-Free Survival and Overall Survival in Patients with Platinum-Resistant Ovarian Cancer, Genmab, 23 October 2026
Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator’s Choice in Participants with Platinum Resistant Ovarian Cancer (RAINFOL-02), ClinicalTrials.gov ID NCT06619236
About the Writer
Neha Vishwakarma (LinkedIn) is a Pharm.D professional with experience in clinical pharmacy, pharmacovigilance, and clinical research. She has hands-on experience in ADR assessment, ICSR processing, medication safety, and clinical data evaluation. Her research background in surgical site infections and antibiotic use supports her focus on evidence-based healthcare writing.