Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)
- 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 Cancer
- Interventions
- Registration Number
- NCT05579366
- Lead Sponsor
- ProfoundBio US Co.
- Brief 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) cohort
Part D: combination therapy cohorts
Part F: a monotherapy endometrial cancer cohort
Part K (United States \[US\] participants only): a monotherapy corrected QT interval (QTc substudy) cohort in high-grade ovarian cancer
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 569
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.
- 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:
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 1 to 3 prior lines of therapy. Participants who had 1 to 4 prior lines of therapy are allowed if mirvetuximab soravtansine (MIRV) was 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.
- 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) 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 (Rina-S+carboplatin):
- Participants must have platinum-sensitive ovarian cancer.
- Participants must have received 1 to 3 prior lines of therapy.
Cohort D2 (Rina-S+bevacizumab):
-
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 (Rina-S+pembrolizumab):
- Endometrial cancer (any subtype excluding sarcoma).
- Participants must have received prior platinum-based chemotherapy for recurrent or advanced disease.
Part F:
- Participants must have histologically or cytologically confirmed endometrial cancer as specified below.
- Advanced, recurrent, metastatic, or primary unresectable endometrial cancer (any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma)
- Participants must have received 1 to 3 prior lines of therapy in advanced, recurrent, or metastatic setting, 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 K (US Participants Only):
- 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 received 1 to 5 prior lines of therapy.
- Participants must have primary platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer.
- 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.
- Prior treatments may have included bevacizumab, PARP inhibitor, and MIRV.
- Measurable disease per the RECIST Version 1.1 at baseline.
- 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.
- Use of a strong cytochrome P450 3A (CYP3A) inhibitor within 14 days (dose escalation only).
- Prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate.
Note: Other protocol-defined inclusion/exclusion may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A, B, C, F and K Rina-S Rina-S monotherapy in Part A and at the recommended dose in Parts B, C, F and K. Part D1 Rina-S Rina-S in combination with carboplatin Part D1 Carboplatin Rina-S in combination with carboplatin Part D2 Rina-S Rina-S in combination with bevacizumab Part D2 Bevacizumab Rina-S in combination with bevacizumab Part D3 Rina-S Rina-S in combination with pembrolizumab Part D3 Pembrolizumab Rina-S in combination with pembrolizumab Part A, B, C and F Rina-S Rina-S monotherapy in Part A and at the recommended dose in Parts B, C and F. Part D1 Rina-S Rina-S in combination with carboplatin Part D1 Carboplatin Rina-S in combination with carboplatin Part D2 Rina-S Rina-S in combination with bevacizumab Part D2 Bevacizumab Rina-S in combination with bevacizumab Part D3 Rina-S Rina-S in combination with pembrolizumab Part D3 Pembrolizumab Rina-S in combination with pembrolizumab
- Primary Outcome Measures
Name Time Method 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) The proportion of participants experiencing DLT.
Parts C and F- Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Through end of treatment, up to approximately 1 year. Participants who achieve partial response (PR) or complete response (CR) per RECIST v1.1 criteria.
Part K (US Participants Only) - Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Findings by Holter Cycles 1 to 3 (each cycle is 21 days)
- Secondary Outcome Measures
Name Time Method Parts A, B, and D - Best Overall Response (BOR) Up to approximately 1 year. 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.
Parts A, B, and D - ORR Up to approximately 1 year. Participants who achieve PR or CR per RECIST v1.1 criteria.
Parts A, B, and D - Disease Control Rate (DCR) Up to approximately 1 year. Participants who achieve stable disease, PR or CR per RECIST v1.1 criteria.
Parts A, B, C, D and F - Progression-Free Survival (PFS) Through end of treatment, up to approximately 1 year. Time from start of treatment to first documented disease progression or death
Parts C and F - Overall survival (OS) Up to approximately 2 years. Time from the start of study treatment to the date of death from any cause
Parts A, B, C, D and F - Duration of Objective Response (DOR) 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. Time from the first documentation of an objective tumor response (CR or PR) to the first documented tumor progression or death
Parts A, B, and D - Peak Plasma Concentration (Cmax) for Rina-S Through end of treatment, up to approximately 1 year. Measurement of maximum plasma concentration after the administration of Rina-S.
Parts A, B, and D - Area Under the Plasma Concentration Versus Time Curve (AUC) for Rina-S Through end of treatment, up to approximately 1 year. Measurement of AUC after the administration of Rina-S.
Parts A, B, and D -Time to Reach Cmax (Tmax) for Rina-S Through end of treatment, up to approximately 1 year Parts A, B, and D - Trough Concentrations (Ctrough) for Rina-S Through end of treatment, up to approximately 1 year Parts A, B, and D - Apparent Terminal Half-life (t1/2) for Rina-S Through end of treatment, up to approximately 1 year Parts C and D - CA-125 Response Determined Using the Gynecologic Cancer Intergroup (GCIG) Criteria Through end of treatment, up to approximately 1 year Parts C, F and K (US Participants Only) - 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) Through end of treatment, up to approximately 1 year
Trial Locations
- Locations (73)
University of California Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
USOR HonorHealth
🇺🇸Phoenix, Arizona, United States
USOR Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
University of California, San Diego; Moores Cancer Center
🇺🇸San Diego, California, United States
USOR Sansum Clinic
🇺🇸Santa Barbara, California, United States
Providence Medical Foundation
🇺🇸Santa Rosa, California, United States
USOR Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
USOR Florida Cancer Specialists North
🇺🇸Saint Petersburg, Florida, United States
USOR Florida Cancer Specialists East
🇺🇸West Palm Beach, Florida, United States
University of Kansas Medical Center (KUMC)
🇺🇸Westwood, Kansas, United States
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