A Study to Investigate Response to Ompenaclid Combined With FOLFIRI Plus Bevacizumab in Patients With Advanced or Metastatic Colorectal Cancer

Sponsor

Inspirna, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05983367

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to measure tumor response to treatment with ompenaclid (RGX-202) 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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Colon Cancer	Drug: Ompenaclid (RGX-202-01) + FOLFIRI + Bevacizumab Drug: Placebo + FOLFIRI + Bevacizumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomized 1:1randomized 1:1

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2026

Anticipated Study Completion Date :

Aug 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RGX-202-01 + 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: Ompenaclid (RGX-202-01) + FOLFIRI + Bevacizumab RGX-202-01 + FOLFIRI + Bevacizumab
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 + FOLFIRI + Bevacizumab Placebo + FOLFIRI + Bevacizumab

Arm

Intervention/Treatment

Experimental: RGX-202-01 + 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: Ompenaclid (RGX-202-01) + FOLFIRI + Bevacizumab

RGX-202-01 + FOLFIRI + Bevacizumab

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 + FOLFIRI + Bevacizumab

Placebo + FOLFIRI + Bevacizumab

Outcome Measures

Primary Outcome Measures

Overall Response Rate [36 months]
The primary objective is to demonstrate that ompenaclid (RGX-202) is superior to placebo in achieving CR or PR (determined as ORR).

Secondary Outcome Measures

Overall Survival [36 months]
Duration of Response [36 months]
Disease Control Rate [36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 dMMR/MSI-H CRC must have also received prior treatment with pembrolizumab or an FDA/EU-approved PD-1/PD-L1 inhibitor. Patients may have received prior treatment with bevacizumab or an EMA-approved biosimilar. Patients who developed metastatic CRC within 12 months of completion of adjuvant oxaliplatin and 5-FU based therapy are also eligible as long as they did not receive an additional first line regimen in the advanced/metastatic setting.
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.
Disease that is measurable by standard imaging techniques by 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.

Exclusion Criteria:

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.