Phase 1/2 Study of Rina-S in Patients With Locally Advanced and/or Metastatic Solid Tumors

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Overview

Rinatabart sesutecan (Rina-S) is an investigational antibody-drug conjugate (ADC) targeting folate receptor-alpha (FRα), currently under evaluation for the treatment of advanced ovarian and endometrial cancers. Recent clinical trials have demonstrated promising antitumor activity in heavily pretreated patients.

Mechanism of Action

Rina-S comprises an anti-FRα monoclonal antibody linked to a topoisomerase I inhibitor. Upon binding to FRα-expressing tumor cells, the ADC is internalized, releasing the cytotoxic payload to induce DNA damage and cell death. (aacrjournals.org)

Efficacy

In the Phase 1/2 RAINFOL-01 study, patients with advanced ovarian cancer received Rina-S at doses of 100 mg/m² or 120 mg/m² every three weeks. The 120 mg/m² cohort exhibited a confirmed objective response rate (ORR) of 55.6% (95% CI: 30.8%-78.5%), including complete responses in 4 patients (2 confirmed) and partial responses in 8 patients (44.4%). The disease control rate (DCR) was 88.9% (95% CI: 65.3%-98.6%), with a median duration of response not reached at a median follow-up of 48 weeks. (inte.medthority.com)

Safety

Rina-S was generally well-tolerated across all doses. Common treatment-emergent adverse events (TEAEs) included anemia, neutropenia, nausea, thrombocytopenia, leukopenia, fatigue, vomiting, alopecia, and diarrhea. Notably, no instances of ocular toxicities, neuropathy, or interstitial lung disease were observed. (globenewswire.com)

Further Reading

• Rinatabart Sesutecan Earns FDA FTD in Platinum-Resistant Ovarian Cancer
• Rina-S Elicits Encouraging Antitumor Activity in Advanced Ovarian Cancer
• Investigational Rinatabart Sesutecan (Rina-S) Shows Promising Anti-Tumor Activity as Single Agent in Heavily Pretreated Patients with Ovarian and Endometrial Cancers in Phase 1/2 Clinical Trial

Last updated: Aug 2025

Inclusion Criteria:

Part A and B:

* Histologically or cytologically confirmed metastatic or unresectable solid malignancy including ovarian cancer (must have epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer), endometrial cancer, non-small cell lung cancer (Part A), EGFR-mutated NSCLC (Part B), breast cancer (hormone receptor positive, HER2-negative and triple-negative) (Part A), mesothelioma.

* Previously received therapies known to confer clinical benefit.

* Measurable disease per RECIST v1.1 for all tumor types other than pleural mesothelioma which will use mRECIST v1.1 at baseline.

Part C:

Participants must have histologically or cytologically confirmed metastatic or unresectable epithelial ovarian cancer as specified below.

* High grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (excluding endometrioid, clear cell carcinomas, mucinous, low grade, and those with a sarcomatous or neuroendocrine element)

* Participants must have received 1 to 3 prior lines of therapy. Participants who had 1 to 4 prior lines of therapy are allowed if mirvetuximab soravtansine (MIRV) was the last line of therapy. Participants must have progressed radiographically on or after their most recent line of therapy.

* Participants must have platinum-resistant ovarian cancer.

* Participants must have received prior bevacizumab.

* Participants with known or suspected deleterious germline or somatic BRCA mutations (as determined by Food and Drug Administration \[FDA\]-approved test in a Clinical Laboratory Improvement Amendments \[CLIA\]-certified laboratory) and who achieved a complete or partial response to platinum-based chemotherapy must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor as maintenance treatment.

* Participants must have known FRα status based on an FDA approved test. Those who are FRα positive must have previously received MIRV, unless the participant has a documented medical exception.

* Participants who are FRα negative, in accordance with the FDA approved test (Ventana folate receptor \[FOLR1\] RxDx Assay), and were treated with MIRV, are excluded.

* Measurable disease per the RECIST v1.1 at baseline.

Part D:

Cohort D1 (Rina-S+carboplatin):

* Participants must have platinum-sensitive ovarian cancer.

* Participants must have received 1 to 3 prior lines of therapy.

Cohort D2 (Rina-S+bevacizumab):

* Participants must have primary platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer.

* Participants with primary platinum-refractory ovarian cancer must have received ≤2 prior lines of therapy. Primary platinum-refractory ovarian cancer is defined as a lack of response or by progression within 91 days after completing front-line platinum containing therapy.

* Participants must have received 1 to 3 prior lines of therapy for platinum-resistant ovarian cancer (PROC), and up to 4 prior lines of therapy for platinum-sensitive ovarian cancer (PSOC). Prior treatments may have included bevacizumab, PARP inhibitor, and MIRV.

* Participants with PSOC must have disease progression on or after maintenance treatment, or at least 6 months (\>183 days) or more from the last dose of platinum-based therapy.

Cohort D3 (Rina-S+pembrolizumab):

* Endometrial cancer (any subtype excluding sarcoma).

* Participants must have received prior platinum-based chemotherapy for recurrent or advanced disease.

Part F:

* Participants must have histologically or cytologically confirmed endometrial cancer as specified below.

* Advanced, recurrent, metastatic, or primary unresectable endometrial cancer (any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma)

* Participants must have received 1 to 3 prior lines of therapy in advanced, recurrent, or metastatic setting, and must have progressed radiographically on or after their most recent line of therapy:

* Participants must have received prior platinum-based chemotherapy and a programmed death-ligand 1 (PD-\[L\])1 inhibitor.

* Participants who progress \>12 months after completion of prior adjuvant or neoadjuvant platinum-based chemotherapy must receive 1 additional cytotoxic systemic treatment prior to enrollment in this study.

* Hormonal therapy alone (i.e., without chemotherapy) will not be counted as a separate line of therapy.

* Measurable disease per the RECIST Version 1.1 at baseline.

Exclusion Criteria:

* History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids within the past 2 years, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

* Use of a strong cytochrome P450 3A (CYP3A) inhibitor within 14 days (dose escalation only).

* Prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate.

Note: Other protocol-defined inclusion/exclusion may apply.