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

NCT03597581 | Completed Phase 1 FDA Drug

• 1 other identifier: RGX-202-001
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 17

Brief 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.

Conditions

Gastrointestinal Cancer; Gastrointestinal Neoplasms; Colorectal Cancer; Colorectal Neoplasms; Colorectal Carcinoma; Gastric Cancer; Gastric Neoplasm; KRAS Mutation-Related Tumors; CRC; Colorectal Cancer Metastatic

Keywords

SLC6a8; Creatine transporter; FOLFIRI; Colorectal Cancer; CRC; KRAS; Colorectal Cancer Metastatic; NRAS; RAS; FOLFOX

Outcome Measures

Primary Outcomes (3)

• RGX-202-01 maximum tolerated dose

  Maximum tolerated dose (MTD), or the maximum tested dose at which multiple dose-limiting toxicities (DLTs) are not observed, of RGX-202-01 as a single agent, and separately, in combination with FOLFIRI +/- bevacizumab.

  6 months

• RGX-202-01 overall response rate

  Overall response rate (ORR) associated with RGX-202-01 treatment in combination with FOLFIRI plus bevacizumab.

  24 months

• RGX-202-01 treatment-emergent adverse events

  Number of participants with treatment-emergent adverse events (TEAEs) with severity as determined by CTCAE v5 associated with RGX-202-01 treatment as a single agent, and separately, in combination with FOLFIRI +/- bevacizumab.

  24 months

Secondary Outcomes (2)

• RGX-202-01 maximum plasma concentration

  24 months

• RGX-202-01 area under the curve

  24 months

Study Arms (5)

Single agent Ompenaclid (RGX-202-01) Dose Escalation

EXPERIMENTAL

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.

Drug: ompenaclid

Ompenaclid (RGX-202-01) in combination with FOLFIRI Dose Escalation

EXPERIMENTAL

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.

Drug: ompenaclid; Drug: FOLFIRI

Expansion: 2nd Line Colorectal Cancer (CRC) KRAS (+)

EXPERIMENTAL

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.

Drug: ompenaclid; Drug: FOLFIRI; Drug: Bevacizumab

Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Escalation

EXPERIMENTAL

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.

Drug: ompenaclid; Drug: Bevacizumab; Drug: FOLFOX regimen

Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Expansion

EXPERIMENTAL

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.

Drug: ompenaclid; Drug: Bevacizumab; Drug: FOLFOX regimen

Interventions

ompenaclid DRUG

RGX-202-01 (ompenaclid) is a small molecule inhibitor of the creatine transporter, SLC6a8.

Also known as: RGX-202-01

Expansion: 2nd Line Colorectal Cancer (CRC) KRAS (+); Ompenaclid (RGX-202-01) in combination with FOLFIRI Dose Escalation; Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Escalation; Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Expansion; Single agent Ompenaclid (RGX-202-01) Dose Escalation

FOLFIRI DRUG

FOLFIRI is a chemotherapy regimen consisting of irinotecan, leucovorin, and 5-fluorouracil. Irinotecan is a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating.

Expansion: 2nd Line Colorectal Cancer (CRC) KRAS (+); Ompenaclid (RGX-202-01) in combination with FOLFIRI Dose Escalation

Bevacizumab DRUG

Bevacizumab is a vascular endothelial growth factor inhibitor.

Expansion: 2nd Line Colorectal Cancer (CRC) KRAS (+); Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Escalation; Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Expansion

FOLFOX regimen DRUG

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

Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Escalation; Ompenaclid (RGX-202-01) in combination with FOLFOX Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must have histologic or cytologic evidence of a RAS colorectal cancer of adenocarcinoma or poorly differentiated histology and must have disease that is resistant to or relapsed following available standard systemic therapy or for which there is no standard systemic therapy or reasonable therapy likely to result in clinical benefit or if such therapy has been refused by the patient.
• The patient must have 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).
• Pathologically documented adenocarcinoma or poorly differentiated locally advanced/metastatic colorectal cancer
• Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator
• Adults ≥18 years
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
• Adequate cardiac function, as defined by left ventricular ejection fraction (LVEF) ≥45%
• Adequate organ function
• Prothrombin time ≤1.5 x ULN or international normalized ratio within ≤1.5; and either partial thromboplastin time or activated partial thromboplastin time ≤1.5 x ULN. Patients on warfarin may be included if on a stable dose with a therapeutic INR \<3.5
• For the expansion stage only, patients must have a tumor that is laboratory-confirmed to be RAS mutant.
• Must have received only one prior standard of care oxaliplatin-containing regimen for locally advanced/metastatic colorectal cancer (CRC)
• Must have received prior treatment with pembrolizumab or an FDA approved PD-1/L1 inhibitor as well, if the patient has dMMR/MSI-H colorectal cancer
• May have received prior treatment with bevacizumab, cetuximab, or panitumumab, or an FDA approved biosimilar.

You may not qualify if:

• Unresolved Grade \> 2 toxicities from prior anticancer therapy; excluding Grade 2 chemotherapy-related neuropathy, alopecia; and excluding Grade 2-3 asymptomatic laboratory abnormalities if considered clinically insignificant by the Investigator, or can be managed with available medical therapies
• Has malignancy of small cell, neuroendocrine, or squamous histology
• Unable to meet the requirement of an adequate treatment washout period before enrollment
• Has additional malignancy that may confound the assessment of study endpoints. Participants with 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 are not excluded
• Has clinically significant cardiovascular disease (New York Heart Association Class III or IV congestive heart failure, history of myocardial infarction, uncontrolled angina, unstable angina or stroke within 6 months before enrollment, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication
• Has clinically active brain or leptomeningeal metastases
• Has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breast feeding
• Has an ongoing chronic hepatopathy of any origin
• Has an evidence of muscular dystrophies or ongoing muscle pathology
• Has oxygen-support requirements
• Has corrected QT interval (QTc) prolongation to \>470 ms (females) or \>450 ms (males)
• Has a physical abnormality or medical condition that limits swallowing multiple pills or has a history of non-adherence to oral therapies
• Has a malabsorption condition, such as short bowel syndrome, impaired GI function or GI disease that may significantly alter absorption, or a high likelihood of impending bowel obstruction, such as strictures
• Has clinically significant ascites (i.e. requiring paracentesis within the preceding 28 days or treatment with pain medication)

Sponsors & Collaborators

• Inspirna, Inc.: lead

Study Sites (17)

Arizona Oncology Associates, PC - HAL

Prescott Valley, Arizona, 86314, United States

Location

Arizona Oncology Associates, PC - HOP E

Tucson, Arizona, 85704, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Sharp HealthCare

San Diego, California, 92123, United States

Location

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

UCLA Department of Medicine

Santa Monica, California, 90404, United States

Location

Medical Oncology Hematology Consultants, PA

Newark, Delaware, 19713, United States

Location

Oncology Hematology West P.C. dba Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Dartmouth

Lebanon, New Hampshire, 03756, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97227, United States

Location

Thomas Jefferson

Philadelphia, Pennsylvania, 19107, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, P.A

McAllen, Texas, 78503, United States

Location

Texas Oncology, P.A

Tyler, Texas, 75702, United States

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Colorectal Neoplasms; Stomach Neoplasms

Interventions

IFL protocol; Bevacizumab; Folfox protocol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Robert Wasserman, MD

  CMO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: July 24, 2018
• Study Start: June 5, 2018
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: April 3, 2025

Record last verified: 2025-03

Locations

US (17)