Investigational Drug
Rinatabart sesutecan
TrialFetch AI Analysis
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Overview
Rinatabart sesutecan (Rina-S; GEN1184, formerly PRO1184) is an investigational antibody–drug conjugate (ADC) directed at folate receptor alpha (FRα), being developed for FRα-expressing solid tumors, notably ovarian and endometrial cancers. As of October 2025, human data from the ongoing Phase 1/2 RAINFOL-01 trial support antitumor activity in heavily pretreated ovarian and endometrial cancer, and a global Phase 3 trial in platinum‑resistant ovarian cancer is recruiting. In August 2025, FDA granted Breakthrough Therapy Designation for advanced endometrial cancer that has progressed after platinum chemotherapy and PD-(L)1 therapy. (ir.genmab.com)
Mechanism of action
- Target: Folate receptor alpha (FRα). (db.antibodysociety.org)
- Payload/linker: An exatecan (topoisomerase I inhibitor) payload coupled via ProfoundBio’s proprietary hydrophilic, protease‑cleavable “sesutecan” linker; reported to enable a homogeneous high DAR (8) and promote efficient payload delivery with favorable ADC properties and bystander effect. (businesswire.com)
Clinical development
- Phase 1/2 (RAINFOL‑01; NCT05579366): Multicenter study with dose escalation and expansion in FRα‑expressing solid tumors (including dedicated ovarian and endometrial cohorts; additional parts include combinations and a QTc substudy). (clinicaltrials.ucsd.edu)
- Phase 3 (NCT06619236): Randomized, open‑label Rina‑S vs investigator’s choice chemotherapy in platinum‑resistant ovarian cancer; recruiting internationally. (dana-farber.org)
- Regulatory: FDA Breakthrough Therapy Designation (Aug 26, 2025) for recurrent/progressive endometrial cancer after platinum and PD‑(L)1; FDA Fast Track Designation (Jan 2024) for FRα‑expressing high‑grade serous/endometrioid platinum‑resistant ovarian cancer. (ir.genmab.com)
Efficacy
- Endometrial cancer (ASCO 2025, RAINFOL‑01 B2 cohort, monotherapy):
- 64 patients received Rina‑S 100 mg/m² (n=22) or 120 mg/m² (n=42) Q3W after prior platinum and PD‑(L)1.
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Confirmed ORR: 50.0% at 100 mg/m² (including 2 CRs); 47.1% at 120 mg/m²; median DOR not reached at 7.7 and 9.8 months’ median follow‑up, respectively. (globenewswire.com)
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Ovarian cancer (PROC; SGO 2025, RAINFOL‑01 B1 cohort, monotherapy):
- Rina‑S 120 mg/m² Q3W: confirmed ORR 55.6% (95% CI 30.8–78.5); median DOR not reached at ~48 weeks’ follow‑up. Responses were seen regardless of FRα expression. (ir.genmab.com)
- Earlier dose‑optimization data at ESMO 2024 showed higher activity at 120 mg/m² vs 100 mg/m² (ORR 50.0% vs 18.2%) in advanced ovarian cancer, informing selection of 120 mg/m² for Phase 3. (globenewswire.com)
Notes: These are noncomparative early‑phase data presented at scientific meetings; Phase 3 results are not yet available. (dana-farber.org)
Safety
- In RAINFOL‑01, commonly reported treatment‑emergent adverse events included diarrhea, nausea, vomiting, fatigue, decreased appetite, constipation, dyspnea, urinary tract infection, and headache. Grade ≥3 AEs occurred in about 32% (100 mg/m²) to 50% (120 mg/m²) of endometrial cancer patients; hematologic toxicities were described as manageable with low discontinuation rates. No ocular toxicity, peripheral neuropathy, or interstitial lung disease signals were reported in the endometrial cohort at the time of ASCO 2025 reporting. (curetoday.com)
Further reading
- Phase 1/2 trial record (RAINFOL‑01; study design and parts). (clinicaltrials.ucsd.edu)
- Phase 3 trial pages (NCT06619236). (dana-farber.org)
- ASCO 2025 program listings (endometrial cohort first disclosure; abstract 3039) and Phase 3 TPS abstract listing. (mfn.se)
- ESMO 2024 mini‑oral abstract (Phase 1/2 dose escalation/expansion overview). (oncologypro.esmo.org)
- AACR 2025 preclinical abstract (mechanism; combination preclinical data). (aacrjournals.org)
- Mechanistic details on sesutecan linker–exatecan payload (SITC 2023 release). (businesswire.com)
- Genmab media releases summarizing RAINFOL‑01 efficacy data (SGO 2025 and ASCO 2025). (ir.genmab.com)
- FDA Breakthrough Therapy Designation announcement in endometrial cancer (Aug 26, 2025). (ir.genmab.com)
Disclosure: Efficacy and safety results cited above are from early‑phase cohorts reported in conference abstracts and company communications; peer‑reviewed full manuscripts were not identified as of October 7, 2025. (oncologypro.esmo.org)
Last updated: Oct 2025
Active trials using Rinatabart sesutecan
Found 4 active trials using this drug:
TrialFetch AI summary: Adults with locally advanced or metastatic non-squamous NSCLC (adenocarcinoma only), ECOG 0–1, measurable disease, and radiographic progression after their most recent therapy (with or without actionable genomic alterations; stable treated brain metastases allowed). Single-arm treatment is rinatabart sesutecan monotherapy q3 weeks, an FRα-targeting antibody–drug conjugate delivering a topoisomerase I inhibitor payload, continued until progression or unacceptable toxicity.
ClinicalTrials.gov ID: NCT07288177
TrialFetch AI summary: Adults with recurrent or progressive endometrial carcinoma (excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma) after 1–3 prior systemic lines including platinum-based chemotherapy and a PD-(L)1 inhibitor, with radiographic progression on/after most recent therapy. Randomized to rinatabart sesutecan (FRα-targeting antibody–drug conjugate delivering a topoisomerase I inhibitor payload) IV q3 weeks vs investigator’s choice single-agent paclitaxel or doxorubicin.
ClinicalTrials.gov ID: NCT07166094
TrialFetch AI summary: Adults with recurrent platinum-sensitive high-grade serous or endometrioid ovarian/fallopian tube/primary peritoneal cancer who have completed second-line platinum doublet chemotherapy and have CR/NED, PR, or stable disease (and BRCA-mut/HRD+ patients must have previously received 1L PARP maintenance) are randomized within 8 weeks to maintenance rinatabart sesutecan plus standard-of-care (bevacizumab maintenance if chosen or observation) versus standard-of-care alone. Rinatabart sesutecan is an FRα-targeted antibody–drug conjugate that delivers an intracellular topoisomerase I inhibitor payload to FRα-expressing tumor cells.
ClinicalTrials.gov ID: NCT07225270
TrialFetch AI summary: Eligible patients are adults with locally advanced or metastatic solid tumors (including ovarian, endometrial, non-small cell lung, breast cancer, and mesothelioma) who have progressed after standard therapies, with cohorts defined by tumor type, platinum sensitivity, and folate receptor alpha (FRα) status. The trial investigates Rina-S (rinatabart sesutecan), a folate receptor alpha-targeted antibody-drug conjugate delivering a topoisomerase I inhibitor, as monotherapy and in combination with carboplatin, bevacizumab, or pembrolizumab depending on cohort.
ClinicalTrials.gov ID: NCT05579366
