Phase 1/2 Study of Rina-S in Patients With Locally Advanced and/or Metastatic Solid Tumors
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
Study locations (37)
USOR HonorHealth
Phoenix, Arizona, 85016
USOR Arizona Oncology Associates
Tucson, Arizona, 85711
University of California Los Angeles Medical Center
Los Angeles, California, 90095
University of California, San Diego; Moores Cancer Center
San Diego, California, 92093
USOR Sansum Clinic
Santa Barbara, California, 93105
Providence Medical Foundation
Santa Rosa, California, 95403
USOR Florida Cancer Specialists South
Fort Myers, Florida, 33908
USOR Florida Cancer Specialists North
St. Petersburg, Florida, 33709
USOR Florida Cancer Specialists East
West Palm Beach, Florida, 33401
Augusta University Georgia Cancer Center
Augusta, Georgia, 30912
University of Kansas Medical Center (KUMC)
Westwood, Kansas, 66205
USOR Maryland Oncology Hematology
Rockville, Maryland, 20850
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Karmanos Cancer Institute
Detroit, Michigan, 48085
START Midwest
Grand Rapids, Michigan, 49503
USOR Minnesota Oncology Hematology
Maplewood, Minnesota, 55109
MD Anderson Cancer Center at Cooper- Two Cooper Plaza
Camden, New Jersey, 08103
Ohio State University Comprehensive Cancer Center (OSUCCC)- The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
University of Oklahoma - Health Sciences Center
Oklahoma City, Oklahoma, 73104
USOR Oncology Associates of Oregon, P.C.
Eugene, Oregon, 97401
Compass Oncology - Rose Quarter
Portland, Oregon, 97227
USOR Alliance Cancer Specialist
Doylestown, Pennsylvania, 18901
Allegheny Health Network
Pittsburgh, Pennsylvania, 15224
Women and Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
Sarah Cannon Research Institute at Tennessee Oncology
Nashville, Tennessee, 37203
Tennessee Oncology
Nashville, Tennessee, 37203
USOR Texas Oncology
Abilene, Texas, 79606
Texas Oncology - Central / South Texas
Austin, Texas, 78758
Mary Crowley Cancer Research
Dallas, Texas, 75521
USOR Texas Oncology
Fort Worth, Texas, 76104
Texas Oncology - Northeast TX
Tyler, Texas, 75702
USOR Texas Oncology Gulf Coast
Woodland, Texas, 77380
START Mountain Region
West Valley City, Utah, 84119
USOR Virginia Cancer Specialists
Fairfax, Virginia, 22031
USOR Virginia Oncology Associates
Norfolk, Virginia, 23502
Swedish Cancer Institute
Seattle, Washington, 98104