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NCT05579366PHASE1, PHASE2Recruiting

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

Genmab

Start Date

12/7/2022

Completion Date

10/1/2027

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Rina-S

DRUG

Carboplatin

DRUG

Bevacizumab

DRUG

Pembrolizumab

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Conditions

High Grade Epithelial Ovarian CancerHigh Grade Serous Ovarian CancerPrimary Peritoneal CarcinomaFallopian Tube CancerEndometrial CancerNon-small Cell Lung CancerEpidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (NSCLC)MesotheliomaBreast AdenocarcinomaTriple Negative Breast CancerHormone Receptor-positive/Her2 Negative Breast CancerPlatinum-resistant Ovarian Cancer (PROC)Platinum Sensitive Ovarian Cancer (PSOC)Primary Refractory Ovarian CancerUterine Cancer

Locations

USOR HonorHealth

Phoenix, Arizona 85016

United States

USOR Arizona Oncology Associates

Tucson, Arizona 85711

United States

University of California Los Angeles Medical Center

Los Angeles, California 90095

United States

University of California, San Diego; Moores Cancer Center

San Diego, California 92093

United States

USOR Sansum Clinic

Santa Barbara, California 93105

United States

Providence Medical Foundation

Santa Rosa, California 95403

United States

USOR Florida Cancer Specialists South

Fort Myers, Florida 33908

United States

USOR Florida Cancer Specialists North

St. Petersburg, Florida 33709

United States

USOR Florida Cancer Specialists East

West Palm Beach, Florida 33401

United States

Augusta University Georgia Cancer Center

Augusta, Georgia 30912

United States

University of Kansas Medical Center (KUMC)

Westwood, Kansas 66205

United States

USOR Maryland Oncology Hematology

Rockville, Maryland 20850

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02215

United States

Karmanos Cancer Institute

Detroit, Michigan 48085

United States

START Midwest

Grand Rapids, Michigan 49503

United States

USOR Minnesota Oncology Hematology

Maplewood, Minnesota 55109

United States

MD Anderson Cancer Center at Cooper- Two Cooper Plaza

Camden, New Jersey 08103

United States

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

Columbus, Ohio 43210

United States

University of Oklahoma - Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

USOR Oncology Associates of Oregon, P.C.

Eugene, Oregon 97401

United States

Compass Oncology - Rose Quarter

Portland, Oregon 97227

United States

USOR Alliance Cancer Specialist

Doylestown, Pennsylvania 18901

United States

Allegheny Health Network

Pittsburgh, Pennsylvania 15224

United States

Women and Infants Hospital of Rhode Island

Providence, Rhode Island 02905

United States

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee 37203

United States

Tennessee Oncology

Nashville, Tennessee 37203

United States

USOR Texas Oncology

Abilene, Texas 79606

United States

Texas Oncology - Central / South Texas

Austin, Texas 78758

United States

Mary Crowley Cancer Research

Dallas, Texas 75521

United States

USOR Texas Oncology

Fort Worth, Texas 76104

United States

Texas Oncology - Northeast TX

Tyler, Texas 75702

United States

USOR Texas Oncology Gulf Coast

Woodland, Texas 77380

United States

START Mountain Region

West Valley City, Utah 84119

United States

USOR Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

USOR Virginia Oncology Associates

Norfolk, Virginia 23502

United States

Swedish Cancer Institute

Seattle, Washington 98104

United States

Cancer hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality

China

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality

China

Hunan Cancer Hospital - Phase 1

Changsha, Hunan

China

Hunan Cancer Hospital - Thoracic Medicine Dept II

Changsha, Hunan

China

Jiangxi Maternal and Child Health Hospital

Nanchang, Jiangxi

China

Jilin Cancer Hospital

Changchun, Jilin

China

Obstetrics & Gynecology Hospital of Fudan University

Chengdu, Shanghai Municipality

China

Fudan University Shanghai Cancer Center - Gynecologic Oncology

Shanghai, Shanghai Municipality

China

Fudan University Shanghai Cancer Center- Phase 1

Shanghai, Shanghai Municipality

China

Shanghai East Hospital

Shanghai, Shanghai Municipality

China

Sichuan Cancer Hospital

Shanghai, Sichuan

China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang

China

Fujian Cancer Hospital

Fujian,

China

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

Guangdong,

China

Second Affiliated Hospital of Zhengzhou University

Henan,

China

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

Hubei,

China

Second Hospital of Shanxi Medical University

Shanxi,

China

Shanxi Cancer Hospital

Shanxi,

China

Liaoning Cancer Hospital & Institute

Shengyang,

China

Tianjin Cancer Hospital

Tianjin,

China

Fukushima Medical University Hospital

Fukushima, Fukushima

Japan

Gunma Prefectural Cancer Center

Ōta, Gunma

Japan

Sapporo Medical University Hospital

Sapporo, Hokkaido

Japan

Hyogo Cancer Center

Akashi, Hyōgo

Japan

Saitama Medical University-International Medical Center

Hidaka, Saitama

Japan

Shizuoka Cancer Center

Nagaizumi-chō, Shizuoka

Japan

Cancer Institute Hospital of JFCR

Koto, Tokyo

Japan

Keio University Hospital

Shinjuku-ku, Tokyo

Japan

Yamagata University Hospital

Yamagata, Yamagata

Japan