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).
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
764
Intravenous infusion of Rina-S
Carboplatin intravenous infusion
Bevacizumab intravenous infusion
Pembrolizumab intravenous infusion
USOR HonorHealth
Phoenix, Arizona, United States
RECRUITINGUSOR Arizona Oncology Associates
Tucson, Arizona, United States
RECRUITINGUniversity of California Los Angeles Medical Center
Los Angeles, California, United States
RECRUITINGUniversity of California, San Diego; Moores Cancer Center
San Diego, California, United States
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, 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
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)
Parts A, B, and D - Best Overall Response (BOR)
Participants who achieve CR or PR. Best response as assessed by the investigator per RECIST v1.1 criteria for all tumor types other than pleural mesothelioma which will use modified RECIST (mRECIST) v1.1.
Time frame: Up to approximately 1 year.
Parts A, B, and D - ORR
Participants who achieve PR or CR per RECIST v1.1 criteria.
Time frame: Up to approximately 1 year.
Parts A, B, and D - Disease Control Rate (DCR)
Participants who achieve stable disease, PR or CR per RECIST v1.1 criteria.
Time frame: Up to approximately 1 year.
Parts A, B, C, D, F, G, H, I, and J - Progression-Free Survival (PFS)
Time from start of treatment to first documented disease progression or death
Time frame: Through end of treatment, up to approximately 1 year.
Parts C, F, G, H, I and J - Overall survival (OS)
Time from the start of study treatment to the date of death from any cause
Time frame: Up to approximately 2 years.
Parts A, B, C, D, F, H, I and J - Duration of Objective Response (DOR)
Time from the first documentation of an objective tumor response (CR or PR) to the first documented tumor progression or death
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, and D - Peak Plasma Concentration (Cmax) for Rina-S
Measurement of maximum plasma concentration after the administration of Rina-S.
Time frame: Through end of treatment, up to approximately 1 year.
Parts A, B, and D - Area Under the Plasma Concentration Versus Time Curve (AUC) for Rina-S
Measurement of AUC after the administration of Rina-S.
Time frame: Through end of treatment, up to approximately 1 year.
Parts A, B, and D -Time to Reach Cmax (Tmax) for Rina-S
Time frame: Through end of treatment, up to approximately 1 year
Parts A, B, and D - Trough Concentrations (Ctrough) for Rina-S
Time frame: Through end of treatment, up to approximately 1 year
Parts A, B, and D - Apparent Terminal Half-life (t1/2) for Rina-S
Time frame: Through end of treatment, up to approximately 1 year
Parts C, D, 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, 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
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USOR Sansum Clinic
Santa Barbara, California, United States
RECRUITINGProvidence Medical Foundation
Santa Rosa, California, United States
RECRUITINGUSOR Florida Cancer Specialists South
Fort Myers, Florida, United States
RECRUITINGUSOR Florida Cancer Specialists North
St. Petersburg, Florida, United States
RECRUITINGUSOR Florida Cancer Specialists East
West Palm Beach, Florida, United States
RECRUITINGAugusta University Georgia Cancer Center
Augusta, Georgia, United States
RECRUITING...and 57 more locations