A Study of RGX-202-01 (Ompenaclid) as Combination Therapy in RAS Mutant Advanced Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title: A Phase 1 Study of RGX-202-01 (Ompenaclid) , a Small Molecule Inhibitor of the Creatine Transporter SLC6a8, as a Single Agent and as Combination Therapy in Patients With Advanced Gastrointestinal Malignancies With Select Expansion Cohorts

Status Recruiting

Clinical Trial Summary

This is a Phase 1 study currently evaluating PO administered ompenaclid in combination with FOLFIRI and bevacizumab in patients with advanced (i.e., locally advanced and unresectable, or metastatic) previously treated colorectal adenocarcinoma. The single agent ompenaclid dose escalation stage and the ompenaclid in combination with FOLFIRI and bevacizumab dose escalation stage of the study has been completed; the expansion stage of ompenaclid in combination with FOLFIRI and bevacizumab is ongoing. In April-24 a protocol amendment added a new dose escalation and expansion stage which will evaluate ompenaclid in combination with FOLFOX and bevacizumab in patients with metastatic CRC. It is anticipated that a total of 30 patients will be enrolled in this new dose escalation and expansion stage of the study.

Clinical Trial Description

Expansion Stage: Ompenaclid in Combination with FOLFIRI and Bevacizumab

Eligible patients must have had PD after receiving only one prior regimen considered standard of care for CRC in the advanced/metastatic setting, which must have been an oxaliplatin-containing regimen. However, if the patient has mismatch repair deficient (dMMR)/ microsatellite instability-high (MSI-H) CRC, they must have also received prior treatment with pembrolizumab or a US Food and Drug Administration (FDA) approved PD-1/PD-L1 inhibitor. Patients who developed recurrent 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.

All patients will receive ompenaclid at a dose of 2400 mg or 3000 mg administered PO BID on a continuous daily schedule. The FOLFIRI dose and schedule will be irinotecan 180 mg/m2 IV over 90 minutes concurrently with leucovorin 400 mg/m2 IV over 2 hours, followed by 5-FU 2400 mg/m2 IV infusion over 46 hours, on Days 1 and 15 of each 28-day cycle, and the bevacizumab dose will be 5 mg/kg on Days 1 and 15 of each 28-day cycle.

The goal of the expansion stage will be to provide further characterization of the efficacy, safety and tolerability of combination therapy, and PK and pharmacodynamics of ompenaclid when combined with FOLFIRI and bevacizumab, at two different dose levels of ompenaclid. The dose of ompenaclid in combination with FOLFIRI and bevacizumab in the expansion stage will be 2400 or 3000 mg PO BID. The 3000 mg BID dose represents the last dose of ompenaclid that has been evaluated in combination with FOLFIRI and bevacizumab in the dose escalation stage and which was not considered to be the MTD. Approximately 52 patients will be treated with ompenaclid in combination with FOLFIRI and bevacizumab, all of whom had/will have CRC.

Dose Escalation and Expansion Stages: Ompenaclid in Combination with FOLFOX and Bevacizumab

Based on experience from the completed single agent and combination therapy dose escalation parts of this study where an MTD was not reached and no DLTs were observed, the dose escalation of ompenaclid in combination with FOLFOX and bevacizumab will evaluate 3 escalating doses of ompenaclid (1800 mg [Cohort 1], 2400 mg [Cohort 2], and 3000 mg [Cohort 3] administered BID PO) on Days 1-28 of a 28-day cycle, in combination with FOLFOX and bevacizumab dosing.

Dose escalation will follow a standard 3+3 design. All safety data from all patients enrolled in each cohort will be reviewed by a Safety Review Committee (SRC) to confirm any DLTs that were experienced and to make a determination regarding enrollment in the next cohort. A patient must have received at least 70% of their total planned ompenaclid doses and both the courses of FOLFOX and bevacizumab planned during the 28-day DLT assessment period with follow-up through the end of this period to be eligible for DLT assessment. If a DLT necessitates enrollment of additional patients into a cohort, all of the safety data for that cohort will be reviewed by the SRC after those additional patients have completed the DLT assessment period.

The goal of the expansion stage will be to provide further characterization of safety and tolerability of combination therapy, and PK and pharmacodynamics of ompenaclid when combined with FOLFOX and bevacizumab at two different dose levels of ompenaclid: the MTD/maximum tested dose as determined in the dose escalation stage, and one dose level below the MTD/maximum tested dose.

A total of approximately 30 patients will be treated with ompenaclid in combination with FOLFOX plus bevacizumab to provide characterization of the safety and tolerability of combination therapy, and PK and pharmacodynamics of ompenaclid when combined with FOLFOX plus bevacizumab. This total includes approximately 10 patients treated at each of the two ompenaclid dose levels during the expansion stage. ;

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Cancer Metastatic
• Colorectal Carcinoma
• Colorectal Neoplasms
• CRC
• Digestive System Neoplasms
• Gastric Cancer
• Gastric Neoplasm
• Gastrointestinal Cancer
• Gastrointestinal Neoplasms
• KRAS Mutation-Related Tumors
• Neoplasms
• Stomach Neoplasms

• NCT number: NCT03597581
• Study type: Interventional
• Source: Inspirna, Inc.
• Contact: Steve Kaesshaefer
• Phone: 1-973-715-2917
• Email: steve.kaesshaefer@inspirna.com
• Status: Recruiting
• Phase: Phase 1
• Start date: June 5, 2018
• Completion date: December 31, 2024