Phase 1/2 Study of Rina-S in Patients With Locally Advanced and/or Metastatic Solid Tumors

Study Identifier:
GCT1184-01 (PRO1184-001
CT.gov Identifier:
NCT05579366
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
N/A
Recruiting

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Study Summary

To test the safety, including side effects, and determine the characteristics of a drug called PRO1184 in participants with solid tumor

To evaluate the safety, tolerability, PK, and antitumor activity of PRO1184 in patients with selected locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non-small cell lung cancer, and mesothelioma

PK, immunogenicity, and antitumor activity will also be evaluated. FRα expression is retrospectively tested.

To study the efficacy and safety of Rina-S in combination with carboplatin, bevacizumab, or pembrolizumab for the treatment of platinum-sensitive OC, PROC, and EC, respectively.

primary endpoint was safety and tolerability of Rina-S

To evaluate the safety and efficacy of rinatabart sesutecan (Rina-S) Q3W at various doses in solid tumors that are known to express FRα. The study consists of multiple parts including Part A dose escalation; 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 (EC) cohort; and Part K monotherapy QTc cohort in high-grade ovarian cancer.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Ovarian
  • Primary Peritoneal
  • Fallopian Tube
  • Endometrial
  • Non-Small Cell Lung Cancer
  • Mesothelioma
  • Breast
  • Breast Cancers
  • Uterine
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part A, B, C, F, G, H, I, J and K Rina-S monotherapy in Part A and at the recommended dose in Parts B, C, F, G, H, I, J and K. Drug: Rina-S Intravenous infusion of Rina-S experimental drug: Rina-S in combination with carboplatin Drug: Rina-S Intravenous infusion of Rina-S Drug: Carboplatin Carboplatin intravenous infusion Experimental: Part D2 and I Rina-S in combination with bevacizumab Drug: Rina-S Intravenous infusion of Rina-S Drug: Bevacizumab Bevacizumab intravenous infusion Experimental: Part D3 and D4 Rina-S in combination with pembrolizumab Drug: Rina-S Intravenous infusion of Rina-S Drug: Pembrolizumab Pembrolizumab intravenous infusion Chinese common name: PRO1184 for injection English common name: PRO1184 for injection Dosage Form: Injection Specification: 100mg/bottle Usage and Dosage: Calculate the patient's body surface area (BSA) through the Moesteller formula, and administer the drug accordingly. The labeled concentration of the reconstituted PRO1184 product is 20 mg/mL. After reconstitution, it should be further diluted to a total volume of 100ml for IV administration. The administration time should be at least 30 minutes, and the infusion rate should not exceed 250 mL/h. Medication schedule: single dose ASCO 2023: PRO1184 is given by intravenous infusion on Day 1 of a 21-day cycle and treatment may continue until disease progression, unacceptable toxicity, or other reason for discontinuation. Part A of the study consists of a dose escalation phase and Part B consists of 4 FR-expressing tumor specific expansion cohorts treated at the RP2D. ASCO 2025 pts with heavily pretreated EC (median 3 prior lines [range 1-8]) received Rina-S 100 mg/m2 (n = 22) or 120 mg/m2 (n = 42) for a median treatment duration of 15.9 weeks. The study consists of multiple parts including 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; and Part F a monotherapy endometrial cancer (EC) cohort. Part A dose escalation; 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 (EC) cohort; and Part K monotherapy QTc cohort in high-grade ovarian cancer.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • 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 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.

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Mountain Region
    West Valley City, UT, United States, 84119
    Investigator
    Justin Call
    Status
    Recruiting
    Condition(s) Treated at Site
    Ovarian
    Primary Peritoneal
    Fallopian Tube
    Endometrial
    Non-Small Cell Lung Cancer
    Mesothelioma
    Breast
    Breast Cancers
    Uterine
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Nehal Lakhani
    Status
    Recruiting
    Condition(s) Treated at Site
    Ovarian
    Primary Peritoneal
    Fallopian Tube
    Endometrial
    Non-Small Cell Lung Cancer
    Mesothelioma
    Breast
    Breast Cancers
    Uterine