RGX-202-01 Combination Therapy for Colorectal Cancer

No longer recruiting at 54 trial locations

Overseen By Stephanie Hansen

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Rgenix, Inc.

Must not be taking: DPD inhibitors, CYP3A4 inhibitors

Disqualifiers: Cardiovascular disease, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced colorectal cancer that has spread or cannot be surgically removed. It examines the effectiveness of a drug called ompenaclid in conjunction with standard chemotherapy treatments, FOLFIRI (a combination of folinic acid, fluorouracil, and irinotecan) and FOLFOX, along with bevacizumab, which helps stop cancer growth by cutting off its blood supply. Individuals with advanced colorectal cancer that did not respond to other treatments and who have a specific gene mutation called RAS might be suitable candidates. The goal is to determine if this combination can control the cancer more effectively. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must meet the requirement of an adequate treatment washout period before enrollment, which means you may need to stop certain medications for a period before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ompenaclid (RGX-202-01) is generally safe for patients. In studies, ompenaclid alone did not cause severe side effects, allowing patients to take it at various doses without major issues. When combined with FOLFIRI and bevacizumab, ompenaclid also proved safe, with no unexpected serious side effects. The combination of ompenaclid with FOLFOX and bevacizumab is newer, and researchers are still collecting information, closely monitoring it for safety.

Overall, current data suggest that ompenaclid, whether used alone or with other treatments, appears safe for people so far. However, since this trial is in an early stage, researchers continue to learn more about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RGX-202-01 for colorectal cancer because it brings something new to the table. While standard treatments like FOLFIRI and FOLFOX involve chemotherapy drugs that target rapidly dividing cancer cells, RGX-202-01, also known as Ompenaclid, offers a novel approach by potentially disrupting cancer cell metabolism. This new mechanism of action could enhance the effectiveness of existing chemotherapy regimens. Additionally, RGX-202-01 is administered orally, which is more convenient than the intravenous methods typically used in standard treatments. This could make it easier for patients to manage their treatment schedules and maintain their quality of life.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that ompenaclid (RGX-202-01) may help treat advanced colorectal cancer. In this trial, some participants will receive ompenaclid alone, which studies have found effective against tumors without severe side effects. Other participants will receive ompenaclid with FOLFIRI (a type of chemotherapy) and bevacizumab, which has proven both effective and safe for patients whose cancer worsened after initial treatments. Additionally, researchers are investigating ompenaclid with FOLFOX (another chemotherapy) to determine if it offers additional benefits. These findings suggest that ompenaclid could be a valuable addition to current colorectal cancer treatments. ^{1 3 4 5 6}

Who Is on the Research Team?

Robert Wasserman, MD

Principal Investigator

CMO

Are You a Good Fit for This Trial?

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

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

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Ompenaclid is administered in combination with FOLFIRI or FOLFOX and bevacizumab to determine the maximum tolerated dose

28-day cycles

Visits on Days 1 and 15 of each cycle

Expansion Stage

Further characterization of efficacy, safety, and pharmacokinetics of ompenaclid in combination with FOLFIRI or FOLFOX and bevacizumab

Ongoing

Visits on Days 1 and 15 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• FOLFIRI
• RGX-202-01

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union as FOLFIRI for:

• Colorectal cancer
• Metastatic colorectal cancer

Approved in United States as FOLFIRI for:

• Colorectal cancer
• Metastatic colorectal cancer

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+

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02163-X/fulltext

575P Phase Ib/II study of ompenaclid (RGX-202-01), a first- ... This is an ongoing Ph 1b/2 study evaluating ompenaclid + FOLFIRI/BEV in 2L mCRC. Pts must have had progression after a 1L oxaliplatin-containing regimen.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03597581?id=NCT03597581&rank=1

NCT03597581 | A Study of RGX-202-01 (Ompenaclid) as ... This is a Phase 1 study currently evaluating PO administered ompenaclid in combination with FOLFIRI and bevacizumab in patients with advanced (i.e., ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.3579

Phase 1b study of RGX-202-01, a first-in-class oral inhibitor ... The objectives of this ongoing Phase 1b study are to evaluate safety, PK/PD, and efficacy of RGX-202-01 in combination with standard-of-care ( ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02673-X/fulltext

646P Phase Ib/II study of ompenaclid (RGX-202-01), afirst ... In a phase 1a study, ompenaclid monotherapy showed objective anti-tumor activity in RASm mCRC without dose-limiting toxicities (DLTs). Methods. Objectives of ...

5. inspirna.com inspirna.com/inspirna-to-present-phase-1b-rgx-202-01-clinical-trial-data-at-the-2022-esmo-world-congress-on-gastrointestinal-cancer/

Inspirna to Present Phase 1b RGX-202-01 Clinical Trial ... Favorable efficacy and safety support further development of RGX-202-01 in advanced or metastatic second-line colorectal cancer.

6. inspirna.com inspirna.com/inspirna-announces-clinical-data-from-phase-1b-2-study-of-ompenaclid-rgx-202-in-advanced-colorectal-cancer-at-esmo-congress-2023/

Inspirna Announces Clinical Data from Phase 1b/2 Study of ... Inspirna Announces Clinical Data from Phase 1b/2 Study of Ompenaclid (RGX-202) in Advanced Colorectal Cancer at ESMO Congress 2023. Encouraging ...