Results from Part C of the Phase 1/2 RAINFOL-01 trial evaluating rinatabart sesutecan (Rina-S; GEN1184) in platinum-resistant ovarian cancer were presented in a late-breaking oral session at the International Gynecologic Cancer Society (IGCS) 2026 Congress, held October 1 – 3, 2026, at the Palais des Congrès de Montréal in Montréal, Canada. Canada. The 109-patient cohort provides the program’s first reported progression-free survival estimate in this setting, with more than half of patients having received three or four prior lines of therapy.
Key Takeaways
- In 109 patients with platinum-resistant ovarian cancer treated in Part C, rinatabart sesutecan 120 mg/m² every three weeks produced a confirmed objective response rate (ORR) of 45.9% (95% CI, 36.3–55.7), including five complete responses.
- The median duration of response was 12.1 months; 51% of responders remained in response at one year; and the median progression-free survival was 9.5 months.
- Antitumor activity was reported across FRα expression levels, including tumors with low or no FRα expression, and in patients previously treated with mirvetuximab soravtansine. The announcement did not provide response rates for these individual subgroups.
- Adverse events led to treatment discontinuation in 5.5% of patients. No safety signals for ocular toxicity, peripheral neuropathy, interstitial lung disease, or stomatitis were identified in the Part C dataset.
- Rinatabart sesutecan is being evaluated in Phase 3 trials across ovarian and endometrial cancer, as well as Phase 2 studies in non-small cell lung cancer and gastrointestinal cancers.
The Clinical Problem
Ovarian cancer is diagnosed in more than 320,000 women worldwide each year. It ranks eighth among cancers in women in incidence and cancer-related deaths. Early symptoms can be nonspecific, and many patients are diagnosed with advanced disease. Initial surgery and platinum-based chemotherapy can produce responses, but relapse is common. Between 70% and 90% of women with advanced-stage disease relapse after first-line treatment, and some progress within six months of their last platinum dose. This group is generally classified as having platinum-resistant disease.
For platinum-resistant ovarian cancer, commonly used systemic treatments include single-agent pegylated liposomal doxorubicin, topotecan, gemcitabine, or paclitaxel. Mirvetuximab soravtansine provides a targeted treatment option for patients whose tumors meet the FRα expression criteria in its FDA-approved indication. The FDA granted accelerated approval in November 2022 and full approval on March 22, 2024, for patients with FRα-positive platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer after one to three prior systemic treatment regimens, with patient selection using an FDA-approved test.
Mechanism of Action
Rinatabart sesutecan consists of a monoclonal antibody directed at folate receptor alpha (FRα), a hydrophilic protease-cleavable linker, and exatecan, a topoisomerase I (TOP1) inhibitor. ProfoundBio developed the linker-drug component, sesutecan. Rinatabart sesutecan is described as having a homogeneous drug-to-antibody ratio (DAR) of 8. Following binding to FRα on the tumor-cell surface, the ADC is internalized and the linker is cleaved enzymatically, releasing the exatecan payload. Preclinical studies reported FRα binding and cytotoxic activity in multiple cell lines and tumor models.
The program entered clinical development as PRO1184. Genmab agreed to acquire ProfoundBio on April 3, 2024, for $1.8 billion in cash and completed the acquisition on May 21, 2024. The transaction included worldwide rights to rinatabart sesutecan, two other clinical candidates, and ProfoundBio’s ADC platforms. The compound now carries the Genmab code GEN1184.
RAINFOL-01 Part C: Who Was Treated
Part C enrolled patients with platinum-resistant high-grade serous ovarian, primary peritoneal, or fallopian tube cancer. Patients received rinatabart sesutecan 120 mg/m² every three weeks as monotherapy and were not selected for FRα expression.
Eligibility allowed 1 to 3 prior lines of therapy, or up to 4 if mirvetuximab soravtansine was the most recent treatment. The enrolled population was heavily pretreated. Median follow-up exceeded one year.
Efficacy Results
The confirmed ORR was 45.9% (95% CI, 36.3–55.7), including five complete responses. Median duration of response was 12.1 months (95% CI, 6.5–15.4), and 51% of responders remained in response at one year.
Median progression-free survival was 9.5 months (95% CI, 7.6–11.3). This was the first progression-free survival estimate reported for rinatabart sesutecan in the program.
The program reported antitumor activity across FRα expression levels, including tumors with low or no FRα expression, and in patients previously treated with mirvetuximab soravtansine. The announcement did not report response rates for the individual FRα-expression or prior-mirvetuximab subgroups.
Part C is a single-arm cohort without a comparator. Its results therefore do not provide a head-to-head comparison with chemotherapy or mirvetuximab soravtansine. Randomized studies will assess comparative efficacy.
Safety and Tolerability
The most frequently reported treatment-emergent adverse events included nausea, fatigue, anemia, neutropenia, vomiting, and decreased platelet count. The announcement reported gastrointestinal events as Grade 1–2.
How Part C Fits With Earlier RAINFOL-01 Data
Part C is the latest of several RAINFOL-01 cohorts. Earlier cohorts evaluated dose selection, activity in ovarian and endometrial cancer, and combination treatment. Dose selection in ovarian cancer (Part B). In September 2024, Genmab reported 42 previously treated patients with advanced ovarian cancer randomized to 100 mg/m² (n = 22) or 120 mg/m² (n = 20) every three weeks.
More than 90% in each arm had platinum-resistant disease. The confirmed ORR was 18.2% at 100 mg/m² and 50.0% at 120 mg/m². Longer follow-up at 120 mg/m² (cohort B1).
A 2025 update of the 120 mg/m² arm, with median on-study follow-up of 48 weeks, reported an ORR of 55.6%, four complete responses (two confirmed), and a disease control rate of 88.9% in patients not selected for FRα expression. Median duration of response had not been reached.
Endometrial cancer (cohort B2). In 64 patients with advanced or recurrent endometrial cancer whose disease had progressed after platinum-based chemotherapy and a PD-(L)1 inhibitor, the confirmed ORR was 50% at 100 mg/m² (n = 22, including two complete responses) and 47.1% at 120 mg/m² (n = 42). Median duration of response had not been reached at median follow-up of 7.7 and 9.8 months, respectively. Grade 3 or higher treatment-emergent adverse events occurred in 31.8% and 50.0% of patients.
Combination with bevacizumab (cohort D2). Presented at the Society of Gynecologic Oncology 2026 Annual Meeting, this cohort treated 40 patients with recurrent ovarian cancer with rinatabart sesutecan 120 mg/m² plus bevacizumab every three weeks, with safety as the primary endpoint. The most common adverse events were nausea (80%), fatigue (67.5%), anemia (55%), and neutropenia (45%). Serious adverse events occurred in 15.0%, adverse events led to dose reductions in 27.5%, and 5% discontinued. No fatal adverse events were reported.
Two FRα-Directed ADCs, Two Different Constructs
Rinatabart sesutecan and mirvetuximab soravtansine target the same antigen but differ in their antibody, payload, linker, conjugation approach, and clinical development strategy.
Mirvetuximab soravtansine’s full approval was supported by the Phase 3 MIRASOL trial, which enrolled 453 patients with FRα-positive platinum-resistant ovarian cancer after up to three prior lines. The ORR was 42% with mirvetuximab soravtansine versus 16% with chemotherapy. Median overall survival was 16.5 months versus 12.7 months (hazard ratio 0.67; 95% CI, 0.50–0.88; P = .0046).
One-third of Part C patients had previously received mirvetuximab soravtansine, and the cohort included tumors with low or no FRα expression. The Part C announcement did not provide subgroup response rates. Further clinical evaluation will determine whether activity is maintained after mirvetuximab soravtansine or in tumors outside the FRα expression population defined for mirvetuximab.
The two ADCs are molecularly distinct, and their clinical safety profiles differ. The available RAINFOL-01 data do not establish a mechanism for those differences or for activity reported in tumors with low or absent FRα expression.
Regulatory Status and Development Program
Rinatabart sesutecan remains investigational, and its safety and efficacy have not been established. The B2 endometrial cohort of RAINFOL-01 supported the Breakthrough Therapy Designation. ProfoundBio received Fast Track designation before the Genmab acquisition.
The clinical program includes four Phase 3 trials in gynecologic cancers and Phase 2 studies in non-small cell lung cancer and advanced gastrointestinal cancers. RAINFOL-02 compares rinatabart sesutecan with investigator’s choice chemotherapy in platinum-resistant ovarian cancer. RAINFOL-03 evaluates rinatabart sesutecan in recurrent or progressive endometrial cancer after platinum-based chemotherapy and PD-(L)1 therapy.
RAINFOL-04 evaluates rinatabart sesutecan plus standard of care versus standard of care as maintenance after second-line platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer. RAINFOL-07 evaluates the drug in second-line platinum-sensitive ovarian cancer. RAINFOL-05 and RAINFOL-09 extend the program into non-small cell lung cancer and advanced gastrointestinal cancers, respectively.
The Part C findings add a larger, longer-followed monotherapy dataset at 120 mg/m² every three weeks in a population that included patients previously treated with mirvetuximab soravtansine and patients with low or no FRα expression. Randomized studies will provide comparative data.
Highlight of Prescribing Information
Mirvetuximab soravtansine (Elahere®; AbbVie)[Prescribing Information]
References
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Featured image: © 2026 CH Hopeful Amid Ovarian Cancer. Used with permission
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