Trial: Rinatabart Sesutecan (Rina-S, PRO1184, …

Trial Details

Sponsor: Genmab (industry)

Phase: 1/2

Start date: Dec. 7, 2022

Planned enrollment: 529

Trial ID: NCT05579366

More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: Rinatabart sesutecan (Rina-S, GEN1184)

TrialFetch AI Analysis

Goal: Evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of Rina-S alone or with other anticancer agents in advanced solid tumors.

Patients: Adults with previously treated, unresectable or metastatic solid tumors, including selected ovarian, endometrial, breast, non-small cell lung, and mesothelioma populations. Eligibility varies by cohort; the platinum-resistant ovarian cancer cohort requires prior bevacizumab and known FRα status, while the endometrial monotherapy cohort requires prior platinum chemotherapy and PD-(L)1 inhibitor therapy.

Design: Nonrandomized, multicohort dose-escalation and expansion study. Participants receive treatment until progression, unacceptable toxicity, or another reason for discontinuation. There is no control arm.

Treatments: Rina-S is studied alone and in separate cohorts with carboplatin, bevacizumab, or pembrolizumab. Rina-S is an investigational antibody–drug conjugate targeting folate receptor alpha (FRα); it delivers exatecan, a topoisomerase I inhibitor, through a cleavable linker. Early single-arm data have shown responses in ovarian and endometrial cancer, but the cohorts are small, some responses are unconfirmed, and comparative benefit has not been established. Carboplatin is platinum chemotherapy, bevacizumab inhibits VEGF, and pembrolizumab inhibits PD-1.

Outcomes: Primary measures are treatment-emergent adverse events in Parts A, B, and D; first-cycle dose-limiting toxicities in Parts A and D; and centrally reviewed objective response rate in Parts C and F. Secondary measures include response and disease control, progression-free survival, duration of response, overall survival in Parts C and F, pharmacokinetics, CA-125 response in relevant ovarian cohorts, and additional adverse-event assessments.

Burden on patient: Estimated moderate to high. Treatment visits, repeated safety assessments, and tumor imaging are expected over potentially many cycles; dose-escalation and pharmacokinetic cohorts may require additional blood draws and closer first-cycle monitoring. No mandatory research biopsy is specified, so the burden may differ substantially between cohorts.

Last updated: Sep 2026

Eligibility

Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.

Show Criteria

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.

Trial Details

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Sites (66)

Cancer hospital, Chinese Academy of Medical Sciences

Fujian Cancer Hospital

Liaoning Cancer Hospital & Institute

Second Affiliated Hospital of Zhengzhou University

Second Hospital of Shanxi Medical University

Shanxi Cancer Hospital

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Tianjin Cancer Hospital

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Chongqing University Cancer Hospital

Hunan Cancer Hospital - Phase 1

Hunan Cancer Hospital - Thoracic Medicine Dept II

Jiangxi Maternal and Child Health Hospital

Jilin Cancer Hospital

Fudan University Shanghai Cancer Center - Gynecologic Oncology

Fudan University Shanghai Cancer Center- Phase 1

Obstetrics & Gynecology Hospital of Fudan University

Shanghai East Hospital

Sichuan Cancer Hospital

Zhejiang Cancer Hospital

Fukushima Medical University Hospital

Gunma Prefectural Cancer Center

Sapporo Medical University Hospital

Hyogo Cancer Center

Saitama Medical University-International Medical Center

Shizuoka Cancer Center

Cancer Institute Hospital of JFCR

Keio University Hospital

Yamagata University Hospital

USOR Arizona Oncology Associates

USOR HonorHealth

Providence Medical Foundation

USOR Sansum Clinic

University of California Los Angeles Medical Center

University of California, San Diego; Moores Cancer Center

USOR Florida Cancer Specialists East

USOR Florida Cancer Specialists North

USOR Florida Cancer Specialists South

Augusta University Georgia Cancer Center

University of Kansas Medical Center (KUMC)

USOR Maryland Oncology Hematology

Dana Farber Cancer Institute

Massachusetts General Hospital

Karmanos Cancer Institute

START Midwest

USOR Minnesota Oncology Hematology

MD Anderson Cancer Center at Cooper- Two Cooper Plaza

Ohio State University Comprehensive Cancer Center (OSUCCC)- The James Cancer Hospital and Solove Research Institute

University of Oklahoma - Health Sciences Center

Compass Oncology - Rose Quarter

USOR Oncology Associates of Oregon, P.C.

Allegheny Health Network

USOR Alliance Cancer Specialist

Women and Infants Hospital of Rhode Island

Sarah Cannon Research Institute at Tennessee Oncology

Tennessee Oncology

Mary Crowley Cancer Research

Texas Oncology - Central / South Texas

Texas Oncology - Northeast TX

USOR Texas Oncology

USOR Texas Oncology

USOR Texas Oncology Gulf Coast

START Mountain Region

USOR Virginia Cancer Specialists

USOR Virginia Oncology Associates