A Study to Investigate Ompenaclid Combined With FOLFIRI Plus Bevacizumab in Advanced/Metastatic Colorectal Cancer

NCT05983367 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: RGX-202-002
• Study Type: interventional
• Target: 76
• Locations: 3 countries
• Sites: 28

Brief Summary

The purpose of this study is to measure tumor response to treatment with ompenaclid (RGX-202-01) in patients with previously treated RAS mutant advanced or metastatic CRC. All patients will receive treatment with FOLFIRI and bevacizumab. In addition, patients will be randomized to receive either ompenaclid 3000 mg BID or matching placebo (herein referred to as Study Drug). Each treatment cycle is 28 days in duration.

Conditions

Colorectal Cancer; Metastatic Colon Cancer

Keywords

Metastatic colon cancer; KRAS colon cancer; CRC advance cancer; malignant colorectal tumor; RAS mutant colon cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  ORR is defined as the proportion of patients achieving a best overall response (BOR) of complete response (CR) or partial response (PR) per the investigators using RECIST version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  From randomization until development of radiographic disease progression (up to approximately 12 months).

Secondary Outcomes (8)

• Progression-Free Survival (PFS)

  From randomization until development of radiographic disease progression or death due to any cause, whichever comes first.

• Overall Survival (OS)

  From randomization until death due to any cause.

• Duration of Response (DoR)

  From randomization until development of radiographic disease progression or death due to any cause, whichever comes first (up to approximately 12 months).

• Disease Control Rate (DCR)

  From randomization until development of radiographic disease progression (up to approximately 12 months).

• Frequency of Adverse Events (AEs)

  From the signing of informed consent until 30 days (+/- 3 days) after the last dose of study drug (up to approximately 12 months).

Study Arms (2)

Ompenaclid + FOLFIRI + Bevacizumab

EXPERIMENTAL

Ompenaclid (RGX-202-01) 3000mg PO (tablets) BID; Irinotecan: 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab: 5 mg/kg on Days 1 and 15 of each 28-day cycle.

Drug: Ompenaclid; Drug: Bevacizumab; Drug: FOLFIRI regimen

Placebo + FOLFIRI + Bevacizumab

PLACEBO COMPARATOR

Placebo (tablets) PO + Irinotecan: 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, followed by 5-FU 2400 mg/m2 over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab: 5 mg/kg on Days 1 and 15 of each 28-day cycle.

Drug: Placebo; Drug: Bevacizumab; Drug: FOLFIRI regimen

Interventions

Ompenaclid DRUG

Ompenaclid (RGX-202-01)

Also known as: RGX-202-01

Ompenaclid + FOLFIRI + Bevacizumab

Placebo DRUG

Placebo

Placebo + FOLFIRI + Bevacizumab

Bevacizumab DRUG

Bevacizumab

Ompenaclid + FOLFIRI + Bevacizumab; Placebo + FOLFIRI + Bevacizumab

FOLFIRI regimen DRUG

FOLFIRI regimen (irinotecan 180 mg/m2 over 90 minutes concurrently with folinic acid 400 mg/m2 over 2 hours, and then 5-FU 2400 mg/m2 over 46 hours on Days 1 and 15 of each 28-day cycle)

Ompenaclid + FOLFIRI + Bevacizumab; Placebo + FOLFIRI + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced disease, defined as cancer that is either metastatic or locally advanced and unresectable and for which additional radiation therapy or other locoregional therapies are not considered feasible.
• Progression of disease after receiving only 1 prior regimen considered standard of care for CRC in the advanced/metastatic setting, and it must have been an oxaliplatin containing regimen. Patients who have mismatch repair deficiency/ high microsatellite instability (dMMR/MSI-H) CRC must have also received prior treatment with pembrolizumab or a Food and Drug Administration (FDA)/European Union (EU)-approved programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitor. Patients may have received prior treatment with bevacizumab or an European Medicines Agency (EMA) approved biosimilar. Patients who developed metastatic CRC within 12 months of completion of adjuvant oxaliplatin and 5-FU based therapy are also eligible.
• Histologic or cytologic evidence of a malignant colorectal tumor of adenocarcinoma or poorly differentiated histology that is laboratory-confirmed to be RAS mutant. Confirmation of RAS mutant status by liquid biopsy is acceptable only if the tumor sample is not available and the liquid biopsy was performed before initiation of the patient's prior treatment regimen. Patients who convert to RAS mutant status after initially having documented wild-type histology are not eligible.
• Disease that is measurable by standard imaging techniques by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. For patients with prior radiation therapy, measurable lesions must be outside of any prior radiation field(s), unless disease progression has been documented at that disease site subsequent to radiation.
• At least 18 years old.
• ECOG performance score ≤ 1.
• Adequate baseline organ function, as demonstrated by the following:
• Calculated creatinine clearance \> 60 mL/min per institutional standard.
• Serum albumin ≥ 2.5 g/dL.
• Bilirubin ≤ 1.5 x institutional upper limit of normal range (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x institutional ULN; patients with hepatic metastases may have AST and ALT ≤ 5 x institutional ULN.
• Absolute neutrophil count (ANC) ≥1.5x109/L.
• Hemoglobin ≥ 8 g/dL and no red blood cell (RBC) transfusions during the prior 14 days.
• Platelet count ≥ 100 x 109/L and no platelet transfusions during the prior 14 days.
• If not taking warfarin (or similar vitamin K inhibitor) the following values are required: international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 x ULN and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤ 1.5 x ULN. Patients on warfarin (or similar vitamin K inhibitor) may be included if on a stable dose with a therapeutic INR \< 3.5.

You may not qualify if:

• Persistent clinically significant toxicities (Grade ≥ 2) from previous anticancer therapy. Excluded are Grade 2 chemotherapy-related neuropathy and alopecia which are permitted and Grade 2 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the Investigator, or can be managed with available medical therapies.
• CRC with histology (or component of histology) consistent with small cell, neuroendocrine, or squamous carcinoma, or lymphoma.
• Received treatment with chemotherapy, external-beam radiation, or other systemic anticancer therapy within 14 days prior to study therapy administration (42 days for prior nitrosourea or mitomycin-C).
• Received treatment with an investigational systemic anticancer agent within 5 half lives of the investigational systemic therapy or within 28 days, whichever is shorter prior to Study Drug administration.
• Has an additional active malignancy that may confound the assessment of the study endpoints. Patients with a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, and melanoma in situ), organ-confined prostate cancer with no evidence of progressive disease.

Sponsors & Collaborators

• Inspirna, Inc.: lead

Study Sites (28)

Imelda Ziekenhuis

Bonheiden, Antwerpen, 2820, Belgium

Location

Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

Location

Institut Jules Bordet

Anderlecht, Belgium

Location

Antwerp University Hospital

Antwerp, 2650, Belgium

Location

UZ Brussel

Brussels, 1090, Belgium

Location

Grand Hoptial De Charleroi

Charleroi, 6000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU de Liège University hospital in Liège

Liège, 4000, Belgium

Location

CHU Nantes -hopital hotel Dieu

Nantes, Loire-Atlantique, 44093, France

Location

CHU Hôpital Jean Minjoz

Besançon, 25000, France

Location

Centre Georges-François Leclerc

Dijon, 21000, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

Groupe Hospitalier Paris Saint Joseph - Oncologie

Paris, 75074, France

Location

Hopital Prive des Cotes d'Armor

Plérin, 22190, France

Location

Institut de Cancerologie de l'Ouest

Saint-Herblain, 44805, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08025, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Puerta de Hierro Majadahonda

Madrid, 28222, Spain

Location

Hospital Puerta de Hierro Majadahonda

Majadahonda, 28220, Spain

Location

Hospital Universitario Virgen de Valme

Seville, 41014, Spain

Location

Hospital Clinico De Valencia

Valencia, 46010, Spain

Location

Hospital Clinico Universitario De Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Operations Officer
• Organization: Inspirna

info@inspirna.com

6463899103

Study Officials

• Osamu Takahashi, MD

  Inspirna, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized 1:1

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 9, 2023
• Study Start: October 10, 2023
• Primary Completion: January 31, 2025
• Study Completion: March 31, 2025
• Last Updated: February 20, 2026
• Results First Posted: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12); FR (8); BE (8)