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

NCT05579366 · Genmab
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Official title
Phase 1/2 Study of Rina-S in Patients With Locally Advanced and/or Metastatic Solid Tumors
About this study
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 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
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 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 and D4: • Endometrial cancer (any subtype excluding sarcoma). 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 design
Enrollment target: 764 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-12-07
Estimated completion: 2027-10
Last updated: 2026-04-07
Interventions
Drug: Rina-SDrug: CarboplatinDrug: BevacizumabDrug: Pembrolizumab
Primary outcomes
  • Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] (Through end of treatment, up to approximately 1 year.)
  • Parts A, and D - Dose Limiting Toxicity (DLT) (At the end of Cycle 1 (each cycle is 21 days))
  • Parts C, F, G, H, I, and J- Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR, Parts C, E, and F) or Investigator (Part G, I, and J) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Through end of treatment, up to approximately 1 year.)
Sponsor
Genmab · industry
Contacts & investigators
ContactGenmab Trial Information · contact · clinicaltrials@genmab.com · +4570202728
InvestigatorStudy Official · study_director, Genmab
All locations (66)
USOR HonorHealthRecruiting
Phoenix, Arizona, United States
USOR Arizona Oncology AssociatesRecruiting
Tucson, Arizona, United States
University of California Los Angeles Medical CenterRecruiting
Los Angeles, California, United States
University of California, San Diego; Moores Cancer CenterRecruiting
San Diego, California, United States
USOR Sansum ClinicRecruiting
Santa Barbara, California, United States
Providence Medical FoundationRecruiting
Santa Rosa, California, United States
USOR Florida Cancer Specialists SouthRecruiting
Fort Myers, Florida, United States
USOR Florida Cancer Specialists NorthRecruiting
St. Petersburg, Florida, United States
USOR Florida Cancer Specialists EastRecruiting
West Palm Beach, Florida, United States
Augusta University Georgia Cancer CenterRecruiting
Augusta, Georgia, United States
University of Kansas Medical Center (KUMC)Recruiting
Westwood, Kansas, United States
USOR Maryland Oncology HematologyRecruiting
Rockville, Maryland, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Dana Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Karmanos Cancer InstituteRecruiting
Detroit, Michigan, United States
START MidwestRecruiting
Grand Rapids, Michigan, United States
USOR Minnesota Oncology HematologyRecruiting
Maplewood, Minnesota, United States
MD Anderson Cancer Center at Cooper- Two Cooper PlazaRecruiting
Camden, New Jersey, United States
Ohio State University Comprehensive Cancer Center (OSUCCC)- The James Cancer Hospital and Solove Research InstituteRecruiting
Columbus, Ohio, United States
University of Oklahoma - Health Sciences CenterRecruiting
Oklahoma City, Oklahoma, United States
USOR Oncology Associates of Oregon, P.C.Recruiting
Eugene, Oregon, United States
Compass Oncology - Rose QuarterRecruiting
Portland, Oregon, United States
USOR Alliance Cancer SpecialistRecruiting
Doylestown, Pennsylvania, United States
Allegheny Health NetworkRecruiting
Pittsburgh, Pennsylvania, United States
Women and Infants Hospital of Rhode IslandRecruiting
Providence, Rhode Island, United States
Sarah Cannon Research Institute at Tennessee OncologyRecruiting
Nashville, Tennessee, United States
Tennessee OncologyRecruiting
Nashville, Tennessee, United States
USOR Texas OncologyRecruiting
Abilene, Texas, United States
Texas Oncology - Central / South TexasRecruiting
Austin, Texas, United States
Mary Crowley Cancer ResearchRecruiting
Dallas, Texas, United States
USOR Texas OncologyRecruiting
Fort Worth, Texas, United States
Texas Oncology - Northeast TXRecruiting
Tyler, Texas, United States
USOR Texas Oncology Gulf CoastRecruiting
Woodland, Texas, United States
START Mountain RegionRecruiting
West Valley City, Utah, United States
USOR Virginia Cancer SpecialistsRecruiting
Fairfax, Virginia, United States
USOR Virginia Oncology AssociatesRecruiting
Norfolk, Virginia, United States
Swedish Cancer InstituteRecruiting
Seattle, Washington, United States
Cancer hospital, Chinese Academy of Medical SciencesRecruiting
Beijing, Beijing Municipality, China
Fujian Cancer HospitalRecruiting
Fujian, China, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityRecruiting
Guangdong, China, China
Second Affiliated Hospital of Zhengzhou UniversityRecruiting
Henan, China, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting
Hubei, China, China
Second Hospital of Shanxi Medical UniversityRecruiting
Shanxi, China, China
Shanxi Cancer HospitalRecruiting
Shanxi, China, China
Liaoning Cancer Hospital & InstituteRecruiting
Shengyang, China, China
Tianjin Cancer HospitalRecruiting
Tianjin, China, China
Chongqing University Cancer HospitalRecruiting
Chongqing, Chongqing Municipality, China
Hunan Cancer Hospital - Phase 1Recruiting
Changsha, Hunan, China
Hunan Cancer Hospital - Thoracic Medicine Dept IIRecruiting
Changsha, Hunan, China
Jiangxi Maternal and Child Health HospitalRecruiting
Nanchang, Jiangxi, China
Jilin Cancer HospitalRecruiting
Changchun, Jilin, China
Obstetrics & Gynecology Hospital of Fudan UniversityRecruiting
Chengdu, Shanghai Municipality, China
Fudan University Shanghai Cancer Center - Gynecologic OncologyRecruiting
Shanghai, Shanghai Municipality, China
Fudan University Shanghai Cancer Center- Phase 1Recruiting
Shanghai, Shanghai Municipality, China
Shanghai East HospitalRecruiting
Shanghai, Shanghai Municipality, China
Sichuan Cancer HospitalRecruiting
Shanghai, Sichuan, China
Zhejiang Cancer HospitalRecruiting
Hangzhou, Zhejiang, China
Fukushima Medical University HospitalRecruiting
Fukushima, Fukushima, Japan
Gunma Prefectural Cancer CenterRecruiting
Ōta, Gunma, Japan
Sapporo Medical University HospitalRecruiting
Sapporo, Hokkaido, Japan
Hyogo Cancer CenterRecruiting
Akashi, Hyōgo, Japan
Saitama Medical University-International Medical CenterRecruiting
Hidaka, Saitama, Japan
Shizuoka Cancer CenterRecruiting
Nagaizumi-chō, Shizuoka, Japan
Cancer Institute Hospital of JFCRRecruiting
Koto, Tokyo, Japan
Keio University HospitalRecruiting
Shinjuku-ku, Tokyo, Japan
Yamagata University HospitalRecruiting
Yamagata, Yamagata, Japan
Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001) · TrialPath