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

February 2, 2026 updated by: Inspirna, Inc.

A Randomized Phase 2 Study of Ompenaclid Versus Placebo in Combination With FOLFIRI Plus Bevacizumab in Patients With Previously Treated RAS Mutant Advanced or Metastatic Colorectal Cancer

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

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.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a Phase 2, randomized, double-blind placebo-controlled study of ompenaclid or matching placebo (Study Drug) in combination with standard-of-care FOLFIRI plus bevacizumab as background therapy in patients with previously treated RAS mutant advanced or metastatic CRC. Randomization will be stratified by whether or not the patient received prior treatment with bevacizumab or an EMA-approved biosimilar. Written informed consent must be obtained prior to initiating any screening activities, except where patients have agreed to the use of previously available tests completed within 28 days of the planned first dose of Study Drug, e.g., computed tomography (CT)/magnetic resonance imaging (MRI) scans. Screening for study eligibility must be completed within 28 days prior to first dose of Study Drug. Patients who are determined to be eligible, based on Screening assessments, will be randomized in the study, and receive their first dose of Study Drug on Cycle 1, Day 1. A treatment cycle is 28 days in duration. Patients will be randomized in a 1:1 ratio to receive oral administration of the five 600-mg tablets BID of ompenaclid or matching placebo (Study Drug). The intravenous FOLFIRI dose and schedule for all patients will be 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. The bevacizumab dose of 5 mg/kg will be administered intravenously on Days 1 and 15 of each 28-day cycle. During treatment, patients will attend study center visits and have study evaluations performed as detailed in the Schedule of Events (Table 1-1). All routine study visits are to be conducted on an outpatient basis. Patients may continue to receive Study Drug until the development of PD, or another discontinuation criterion is met, including unacceptable toxicity, voluntary withdrawal from treatment, or closure of the study by the Sponsor; no maximum duration of therapy has been set. After discontinuation of the Study Drug, patients will complete an End of Treatment (EOT) visit within 21 days after their last dose of Study Drug. Safety follow-up is to be conducted by telephone 30 days (+/- 3 days) after their last dose of Study Drug and longer if drug-related AEs have not resolved at that time. Patients and/or their health care providers will also be contacted by telephone approximately every 90 days for information on evidence of PD in settings in which discontinuation of Study Drug was for reasons other than PD, such as an adverse event (AE) or investigator discretion, and/or for assessment of survival status (tumor measurements as specified in the protocol are not required after the EOT visit). This extended follow-up for disease status and survival after discontinuation of the Study Drug may continue until the target number of disease progression events have been observed or for 12 months after the patient's EOT visit, whichever is later. The End of Study for a given patient is defined as the date of the last extended follow-up disease/survival status, or until death, withdrawal of consent, loss to follow-up, or study closure, whichever occurs first.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
76

Phase

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.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Inspirna
  • Phone Number: (646) 856-9261

Study Locations

  • Belgium
      • Anderlecht, Belgium
        • Institut Jules Bordet
      • Antwerp, Belgium, 2650
        • Antwerp University Hospital
      • Brussels, Belgium, 1090
        • UZ Brussel
      • Charleroi, Belgium, 6000
        • Grand Hoptial De Charleroi
      • Leuven, Belgium, 3000
        • UZ Leuven
      • Liège, Belgium, 4000
        • CHU de Liège University hospital in Liège
    • Antwerpen
      • Bonheiden, Antwerpen, Belgium, 2820
        • Imelda Ziekenhuis
    • Brussels Capital
      • Woluwe-Saint-Lambert, Brussels Capital, Belgium, 1200
        • Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
  • France
      • Besançon, France, 25000
        • CHU Hôpital Jean Minjoz
      • Dijon, France, 21000
        • Centre Georges-François Leclerc
      • Marseille, France, 13009
        • Institut Paoli-Calmettes
      • Paris, France, 75074
        • Groupe Hospitalier Paris Saint Joseph - Oncologie
      • Plérin, France, 22190
        • Hôpital Privé Des Côtes d'Armor
      • Saint-Herblain, France, 44805
        • Institut de Cancérologie de l'Ouest
      • Villejuif, France, 94805
        • Institut Gustave Roussy
    • Loire-Atlantique
      • Nantes, Loire-Atlantique, France, 44093
        • CHU Nantes -hopital hotel Dieu
  • Spain
      • Barcelona, Spain, 08003
        • Hospital Del Mar
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall D Hebron
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28222
        • Hospital Puerta de Hierro Majadahonda
      • Majadahonda, Spain, 28220
        • Hospital Puerta de Hierro Majadahonda
      • Seville, Spain, 41014
        • Hospital Universitario Virgen de Valme
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain, 46010
        • Hospital Clínico de Valencia
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
    • Catalonia
      • Barcelona, Catalonia, Spain, 08025
        • Hospital de La Santa Creu i Sant Pau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. At least 18 years old.
  6. ECOG performance score ≤ 1.

  7. Adequate baseline organ function, as demonstrated by the following:

    1. Calculated creatinine clearance > 60 mL/min per institutional standard.
    2. Serum albumin ≥ 2.5 g/dL.
    3. Bilirubin ≤ 1.5 x institutional upper limit of normal range (ULN).
    4. 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.
    5. Absolute neutrophil count (ANC) ≥1.5x109/L.
    6. Hemoglobin ≥ 8 g/dL and no red blood cell (RBC) transfusions during the prior 14 days.
    7. Platelet count ≥ 100 x 109/L and no platelet transfusions during the prior 14 days.
  8. 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.
  9. Left ventricular ejection fraction (LVEF) x 45% as determined by either echocardiography (ECHO) or multigated acquisition (MUGA) scanning.
  10. Woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 2 weeks prior to treatment.
  11. Men and WOCBP must agree to use acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for at least 6 months from the last dose of bevacizumab or 2 months after the last dose of ompenaclid, whichever is longer.
  12. Provides signed informed consent prior to initiation of any study-specific procedures or treatment.
  13. Able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment

Exclusion Criteria:

  1. 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.
  2. CRC with histology (or component of histology) consistent with small cell, neuroendocrine, or squamous carcinoma, or lymphoma.
  3. 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).
  4. 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.
  5. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ompenaclid + FOLFIRI + Bevacizumab
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: Bevacizumab
Bevacizumab
Drug: FOLFIRI regimen
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)
Drug: Ompenaclid
Ompenaclid (RGX-202-01)
Other Names:
  • RGX-202-01
Placebo Comparator: Placebo + FOLFIRI + Bevacizumab
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
Placebo
Drug: Bevacizumab
Bevacizumab
Drug: FOLFIRI regimen
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: From randomization until development of radiographic disease progression (up to approximately 12 months).
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: From randomization until development of radiographic disease progression or death due to any cause, whichever comes first.
PFS is defined as the time from the date of randomization to the date of objectively determined progressive disease (PD) per the investigators using RECIST version 1.1 or death from any cause, whichever occurs first (up to approximately 12 months).
From randomization until development of radiographic disease progression or death due to any cause, whichever comes first.
Overall Survival (OS)
Time Frame: From randomization until death due to any cause.
OS is defined as the time from the date of randomization to the date of death from any cause. The proportions of participants who have not experienced OS events (death) at 9 months and 12 months are presented.
From randomization until death due to any cause.
Duration of Response (DoR)
Time Frame: From randomization until development of radiographic disease progression or death due to any cause, whichever comes first (up to approximately 12 months).
DoR is defined as the time from the date of objectively determined PR or CR (whichever status is recorded first) to the date of PD per the investigators using RECIST version 1.1 or death from any cause, whichever occurs first. The median DoR was not reached in both groups.
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)
Time Frame: From randomization until development of radiographic disease progression (up to approximately 12 months).
DCR is defined as the proportion of patients achieving a BOR of CR, PR, or stable disease (SD).
From randomization until development of radiographic disease progression (up to approximately 12 months).
Frequency of Adverse Events (AEs)
Time Frame: From the signing of informed consent until 30 days (+/- 3 days) after the last dose of study drug (up to approximately 12 months).
Percentage of patients with treatment-emergent AEs (TEAE).
From the signing of informed consent until 30 days (+/- 3 days) after the last dose of study drug (up to approximately 12 months).
Pharmacokinetics of Ompenaclid
Time Frame: At Cycle 1 day 15 and Cycle 2 day 15 (each cycle is 28 days in length)
Steady state concentration of ompenaclid.
At Cycle 1 day 15 and Cycle 2 day 15 (each cycle is 28 days in length)
Exploratory Biomarkers That May Correlate With Efficacy Outcomes
Time Frame: At baseline
Creatine kinase B (CKB) levels identified in baseline tumor tissue samples analyzed retrospectively.
At baseline
Progression-Free Survival (PFS) Rate at 6 and 9 Months
Time Frame: From randomization until development of radiographic disease progression or death due to any cause, whichever comes first.
PFS is defined as the time from the date of randomization to the date of objectively determined progressive disease (PD) per the investigators using RECIST version 1.1 or death from any cause, whichever occurs first. The proportions of participants who have not experienced PFS events (radiological disease progression or death) at 6 months and 9 months are presented.
From randomization until development of radiographic disease progression or death due to any cause, whichever comes first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Inspirna, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Osamu Takahashi, MD, Inspirna, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 10, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 1, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RGX-202-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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