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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT05579366Sponsor: GenmabLast updated: 2026-06-03

Summary

This study will test the safety, including side effects, and determine the characteristics of a drug called Rina-S in participants with solid tumors. Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable).

Detailed description

This is a Phase 1/2 study of Rina-S; also known as GEN1184, formerly known as PRO1184, a folate receptor alpha (FRα) targeted antibody-drug conjugate, to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of Rina-S in participants with selected locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non-small cell lung cancer, and mesothelioma. The study consists of multiple parts: Part A: monotherapy cohorts Part B: tumor-specific monotherapy dose-expansion cohorts Part C: platinum-resistant ovarian cancer (PROC) monotherapy cohort Part D: combination therapy cohorts Part E: a monotherapy PROC cohort Parts F and G: a monotherapy endometrial cancer (EC) cohort Part H: a monotherapy PROC cohort Part I: platinum-sensitive ovarian cancer (PSOC) cohort Part J: a monotherapy PROC cohort Part K: a monotherapy high-grade ovarian cancer cohort Participants will continue to receive study treatment until the first instance of disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the Sponsor, pregnancy, or death.

Arms & interventions

  • DrugRina-S

    Intravenous infusion of Rina-S

  • DrugCarboplatin

    Carboplatin intravenous infusion

  • DrugBevacizumab

    Bevacizumab intravenous infusion

  • DrugPembrolizumab

    Pembrolizumab intravenous infusion

Outcome measures

Primary

  • Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]

    Time frame: Through end of treatment, up to approximately 1 year.

  • Parts A, and D - Dose Limiting Toxicity (DLT)

    The proportion of participants experiencing DLT.

    Time frame: At the end of Cycle 1 (each cycle is 21 days)

  • Parts C, E, F, G, H, I, and J- Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR, Parts C and F) or Investigator (Part E, G, I, and J) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Participants who achieve partial response (PR) or complete response (CR) per RECIST v1.1 criteria.

    Time frame: Through end of treatment, up to approximately 1 year.

  • Part K (US Participants Only) - Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Findings by Holter

    Time frame: Cycles 1 to 3 (each cycle is 21 days)

Secondary

  • Parts A, B, and D - Best Overall Response (BOR)

    Time frame: Up to approximately 1 year.

  • Parts A, B, D, and E - ORR

    Time frame: Up to approximately 1 year.

  • Parts A, B, and D - Disease Control Rate (DCR)

    Time frame: Up to approximately 1 year.

  • Parts A, B, C, D, E, F, G, H, I, and J - Progression-Free Survival (PFS)

    Time frame: Through end of treatment, up to approximately 1 year.

  • Parts C, E, F, G, H, I and J - Overall survival (OS)

    Time frame: Up to approximately 2 years.

  • Parts A, B, C, D, E, F, H, I and J - Duration of Objective Response (DOR)

    Time frame: From date of enrollment until the date of first documented disease progression or date of study withdrawal, whichever came first, assessed up to 12 months.

  • Parts A, B, D, and E - Peak Plasma Concentration (Cmax) for Rina-S

    Time frame: Through end of treatment, up to approximately 1 year.

  • Parts A, B, D, and E - Area Under the Plasma Concentration Versus Time Curve (AUC) for Rina-S

    Time frame: Through end of treatment, up to approximately 1 year.

  • Parts A, B, D, and E -Time to Reach Cmax (Tmax) for Rina-S

    Time frame: Through end of treatment, up to approximately 1 year

  • Parts A, B, D, and E - Trough Concentrations (Ctrough) for Rina-S

    Time frame: Through end of treatment, up to approximately 1 year

  • Parts A, B, D, and E- Apparent Terminal Half-life (t1/2) for Rina-S

    Time frame: Through end of treatment, up to approximately 1 year

  • Parts C, D, E, H and J - CA-125 Response Determined Using the Gynecologic Cancer Intergroup (GCIG) Criteria

    Time frame: Through end of treatment, up to approximately 1 year

  • Parts C, E, F, H, I, J, and K - Number of Participants with Type, Incidence, Severity, Seriousness as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and Relatedness of Adverse Events (AEs)

    Time frame: Through end of treatment, up to approximately 1 year

  • Part E - Number of Participants With Antidrug Antibodies (ADA)

    Time frame: Through end of treatment, up to approximately 1 year

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 or cervical cancer (Part B). * 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, E, and H: 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 up to 3 prior lines of therapy. Participants may have had up to to 4 prior lines of therapy are allowed if MIRV is locally approved and was used as 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 or approved biosimilar. * 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; or locally approved equivalent) 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. * Measurable disease per the RECIST v1.1 at baseline. Part D: Cohort D1: * Participants must have platinum-sensitive ovarian cancer. * Participants must have received 1 to 3 prior lines of therapy. Cohort D2: * 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: • Endometrial cancer (any subtype excluding sarcoma). Cohort D4: • Primary advanced or recurrent endometrial cancer (any subtype excluding sarcoma and neuroendocrine tumors). Part F and G: * Participants must have histologically or cytologically confirmed EC. * Recurrent progressive EC (any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma) following prior therapy. * Participants must have received 1 to 3 prior lines of therapy, 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. Part I: * Participants must have histologically or cytologically confirmed high grade serous or endometrioid epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer (excluding clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies or low grade/borderline ovarian tumors). * Participants must have platinum sensitive ovarian cancer. * Measurable disease per the RECIST Version 1.1 at baseline. Part J: * Participants must have high grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including serous, endometrioid, and clear cell carcinomas, and excluding mucinous, low grade, and those with a sarcomatous or neuroendocrine element. * Measurable disease per the RECIST Version 1.1 at baseline. Part K: * Participants must have histologically or cytologically confirmed metastatic or unresectable ovarian cancer (must have high grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including serous, endometrioid, and clear cell carcinomas, and excluding mucinous, low grade, and those with a sarcomatous or neuroendocrine element). * Participants must have primary platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer. * 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. * Prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate. Note: Other protocol-defined inclusion/exclusion may apply.

Study locations (37)

USOR HonorHealth

Phoenix, Arizona, 85016

Recruiting

USOR Arizona Oncology Associates

Tucson, Arizona, 85711

Recruiting

University of California Los Angeles Medical Center

Los Angeles, California, 90095

Recruiting

University of California, San Diego; Moores Cancer Center

San Diego, California, 92093

Recruiting

USOR Sansum Clinic

Santa Barbara, California, 93105

Recruiting

Providence Medical Foundation

Santa Rosa, California, 95403

Recruiting

USOR Florida Cancer Specialists South

Fort Myers, Florida, 33908

Recruiting

USOR Florida Cancer Specialists North

St. Petersburg, Florida, 33709

Recruiting

USOR Florida Cancer Specialists East

West Palm Beach, Florida, 33401

Recruiting

Augusta University Georgia Cancer Center

Augusta, Georgia, 30912

Recruiting

University of Kansas Medical Center (KUMC)

Westwood, Kansas, 66205

Recruiting

USOR Maryland Oncology Hematology

Rockville, Maryland, 20850

Recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

Karmanos Cancer Institute

Detroit, Michigan, 48085

Recruiting

START Midwest

Grand Rapids, Michigan, 49503

Recruiting

USOR Minnesota Oncology Hematology

Maplewood, Minnesota, 55109

Recruiting

MD Anderson Cancer Center at Cooper- Two Cooper Plaza

Camden, New Jersey, 08103

Recruiting

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

Columbus, Ohio, 43210

Recruiting

University of Oklahoma - Health Sciences Center

Oklahoma City, Oklahoma, 73104

Recruiting

USOR Oncology Associates of Oregon, P.C.

Eugene, Oregon, 97401

Recruiting

Compass Oncology - Rose Quarter

Portland, Oregon, 97227

Recruiting

USOR Alliance Cancer Specialist

Doylestown, Pennsylvania, 18901

Recruiting

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224

Recruiting

Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905

Recruiting

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203

Recruiting

Tennessee Oncology

Nashville, Tennessee, 37203

Recruiting

USOR Texas Oncology

Abilene, Texas, 79606

Recruiting

Texas Oncology - Central / South Texas

Austin, Texas, 78758

Recruiting

Mary Crowley Cancer Research

Dallas, Texas, 75521

Recruiting

USOR Texas Oncology

Fort Worth, Texas, 76104

Recruiting

Texas Oncology - Northeast TX

Tyler, Texas, 75702

Recruiting

USOR Texas Oncology Gulf Coast

Woodland, Texas, 77380

Recruiting

START Mountain Region

West Valley City, Utah, 84119

Recruiting

USOR Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting

USOR Virginia Oncology Associates

Norfolk, Virginia, 23502

Recruiting

Swedish Cancer Institute

Seattle, Washington, 98104

Recruiting
Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001) | Cancerify