RGX-202-01 Combination Therapy for Colorectal Cancer

Recruiting at54 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Rgenix, Inc.

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Research Team

Robert Wasserman, MD

Principal Investigator

CMO

Eligibility Criteria

Adults over 18 with RAS mutant advanced colorectal cancer that's resistant or relapsed after standard therapy, or when no effective standard therapy exists. Participants must have had only one prior oxaliplatin-based treatment for metastatic CRC and may have used certain other drugs like pembrolizumab. They need to be in good physical condition (ECOG PS 0-1), not pregnant, and without serious heart disease, infections, or psychiatric conditions.

Inclusion Criteria

My heart pumps well, with an ejection fraction of 45% or higher.

My blood clotting tests are within normal limits and if on warfarin, my dose is stable with INR <3.5.

My organs are functioning well.

Exclusion Criteria

Patient has corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (males)

I have a condition that affects how my body absorbs nutrients.

I have a history of bleeding disorders or tend to develop blood clots.

Treatment Details

Interventions

• Bevacizumab (Angiogenesis Inhibitor)
• FOLFIRI (Chemotherapy Agent)
• RGX-202-01 (Small Molecule Inhibitor)

Trial Overview The trial is testing RGX-202-01 (Ompenaclid) alone and combined with FOLFIRI +/- bevacizumab in patients who've progressed on standard therapies. It starts by finding the best dose of RGX-202-01 then moves to treating more patients at this dose to see how well it works specifically for those with RAS mutant colorectal cancer.

Participant Groups

Group I: Single agent Ompenaclid (RGX-202-01) Dose Escalation Experimental Treatment 1 Intervention

Ompenaclid (RGX-202-01) is administered orally twice or three times daily on days 1-28 of each 28-day cycle. The dose regimen is dependent on the cohort in which the patient is enrolled.

Group II: Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Expansion Experimental Treatment 3 Interventions

Ompenaclid (RGX-202-01) is administered orally twice or three times daily on days 1-28 of each 28-day cycle. The dose regimen is dependent on the cohort in which the patient is enrolled. The FOLFOX regimen used for this protocol consists of oxaliplatin given at 85 mg/m2 IV together with leucovorin at 400 mg/m2 IV (substitution with levo-leucovorin 200 mg/m2 IV is allowed) (duration per institutional policy), followed by a 5-FU bolus of 400 mg/m2 (over 2-5 minutes), and then continuous infusional 5-FU given at a dose of 2400 mg/m2 over 46-48 hours (1200 mg/m2/day), given on Days 1 and 15 of each 28-day cycle. A minimum of 8 FOLFOX cycles should be received if tolerated per standard of care guidelines.

Group III: Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Escalation Experimental Treatment 3 Interventions

RGX-201-01 is administered orally twice or three times daily on days 1-28 of each 28-day cycle. The dose regimen is dependent on the cohort in which the patient is enrolled. The FOLFOX regimen used for this protocol consists of oxaliplatin given at 85 mg/m2 IV together with leucovorin at 400 mg/m2 IV (substitution with levo-leucovorin 200 mg/m2 IV is allowed) (duration per institutional policy), followed by a 5-FU bolus of 400 mg/m2 (over 2-5 minutes), and then continuous infusional 5-FU given at a dose of 2400 mg/m2 over 46-48 hours (1200 mg/m2/day), given on Days 1 and 15 of each 28-day cycle. A minimum of 8 FOLFOX cycles should be received if tolerated per standard of care guidelines.

Group IV: Ompenaclid (RGX-202-01) in combination with FOLFIRI Dose Escalation Experimental Treatment 2 Interventions

Ompenaclid (RGX-202-01) is administered orally twice or three times daily on days 1-28 of each 28-day cycle. The dose regimen is dependent on the cohort in which the patient is enrolled. FOLFIRI is administered as follows: irinotecan 180 mg/m2 intravenously over 90 minutes concurrently with folinic acid (leucovorin) 400 mg/m2 intravenously over 2 hours, followed by 5-FU 400 mg/m2 intravenous bolus and then 5-FU 2400 mg/m2 intravenous infusion over 46 hours, on Days 1 and 15 of each 28-day cycle.

Group V: Expansion: 2nd Line Colorectal Cancer (CRC) KRAS (+) Experimental Treatment 3 Interventions

2nd Line CRC RAS (+) Ompenaclid (RGX-202-01) is administered orally twice on days 1-28 of each 28-day cycle. FOLFIRI is administered as follows: irinotecan 180 mg/m2 intravenously over 90 minutes concurrently with folinic acid (leucovorin) 400 mg/m2 intravenously over 2 hours, followed by 5-FU 400 mg/m2 intravenous bolus and then 5-FU 2400 mg/m2 intravenous infusion over 46 hours, on Days 1 and 15 of each 28-day cycle. Bevacizumab is administered as follows: 5 mg/kg on Days 1 and 15 of each 28-day cycle.

FOLFIRI is already approved in Canada, Japan for the following indications:

Approved in Canada as FOLFIRI for:

• Colorectal cancer
• Metastatic colorectal cancer

Approved in Japan as FOLFIRI for:

• Colorectal cancer
• Metastatic colorectal cancer

Who Is Running the Clinical Trial?

Rgenix, Inc.

Lead Sponsor

Trials

3

Recruited

260+

Inspirna, Inc.

Lead Sponsor

Trials

3

Recruited

320+