A Study of RGX-202-01 (Ompenaclid) as Combination Therapy in 2nd Line RAS Mutant Advanced Colorectal Cancer

October 4, 2023 updated by: Inspirna, Inc.

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

RGX-202-01 (ompenaclid) is a Phase 1, first-in-human, dose escalation and expansion study of RGX-202-01 as a single agent and in combination with FOLFIRI +/- bevacizumab. RGX-202-01 is a small molecule inhibitor of the creatine transporter SLC6a8, a novel metabolic target that drives gastrointestinal cancer progression.

During the dose escalation stage, multiple doses of orally administered RGX-202-01 with or without FOLFIRI +/- bevacizumab (single agent or combination therapy) will be evaluated in patients with advanced gastrointestinal tumors (i.e., locally advanced and unresectable, or metastatic) who have had PD on available standard systemic therapies or for which there are no standard systemic therapies of relevant clinical impact.

In the expansion stage: Patients with colorectal cancer (CRC) RAS Mutant will be treated at the optimal dose.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Prescott Valley, Arizona, United States, 86314
      • Tucson, Arizona, United States, 85704
        • Recruiting
        • Arizona Oncology Associates, PC - HOP E
        • Contact:
        • Principal Investigator:
          • Suresh Mukkamala
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Contact:
        • Principal Investigator:
          • Andrew Hendifar, MD
      • San Diego, California, United States, 92123
        • Completed
        • Sharp HealthCare
      • Santa Barbara, California, United States, 93105
        • Recruiting
        • Sansum Clinic
        • Contact:
        • Principal Investigator:
          • Mukul Gupta, MD
      • Santa Monica, California, United States, 90404
        • Recruiting
        • UCLA Department of Medicine
        • Contact:
          • Rosen, MD
          • Phone Number: 310-633-8400
        • Principal Investigator:
          • Lee Rosen, MD
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Medical Oncology Hematology Consultants, PA
        • Principal Investigator:
          • Jamal Misleh
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Oncology Hematology West P.C. dba Nebraska Cancer Specialists
        • Contact:
        • Principal Investigator:
          • Joel Michalski
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
    • New York
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Andrea Cercek, MD
          • Phone Number: 646-888-4189
        • Principal Investigator:
          • Andrea Cercek, MD
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina Chapel Hill
        • Contact:
        • Principal Investigator:
          • Hanna Sanoff, MD
    • Oregon
      • Portland, Oregon, United States, 97227
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson
        • Contact:
        • Contact:
          • Phone Number: 267-584-9165
        • Principal Investigator:
          • Atrayee BasuMallick
    • South Carolina
      • Greenville, South Carolina, United States, 29605
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Tennessee Oncology
        • Principal Investigator:
          • David Spigel, MD
        • Contact:
    • Texas
      • McAllen, Texas, United States, 78503
      • Tyler, Texas, United States, 75702

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Inclusion Criteria for RGX-202-01 plus FOLFIRI and bevacizumab expansion stages:

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.

Exclusion Criteria:

  • 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)
  • Has a medical condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities

Exclusion Criteria for RGX-202-01 plus FOLFIRI and bevacizumab dose escalation and expansion stages:

  • Has known dihydropyrimidine dehydrogenase (DPD) deficiency or is on treatment with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine, within 4 weeks prior to the start of treatment
  • Has known homozygous or heterozygous for UGT1A1*28, UGT1A1*6, UGT1A9*1 or ABCG2 allele
  • Require treatment with strong CYP3A4 inhibitors or strong UGT1A1 inhibitors
  • Previously treated with FOLFIRI or other irinotecan containing regimens
  • Has proteinuria ≥ 2gm/24 and/or nephrotic syndrome. Patients with a proteinuria 2+ or greater urine dipstick reading should undergo further assessment, e.g., a 24-hour urine collection
  • History of acute or subacute intestinal occlusion - except if such an event occurred only around the time of diagnosis - or chronic inflammatory bowel disease or chronic diarrhea
  • History of severe, non-healing wounds, ulcers or bone fractures
  • History of arterial thromboemboli or severe hemorrhage within 6 months of prior FOLFIRI treatment with an exception of tumor bleeding before tumor resection surgery
  • History of hemorrhagic diathesis or tendency towards thrombosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single agent RGX-202-01 Dose Escalation
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.
Drug: RGX-202-01
RGX-202-01 is a small molecule inhibitor of the creatine transporter, SLC6a8.
Experimental: RGX-202-01 in combination with FOLFIRI Dose Escalation

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.

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: RGX-202-01
RGX-202-01 is a small molecule inhibitor of the creatine transporter, SLC6a8.
Drug: FOLFIRI
FOLFIRI is a chemotherapy regimen consisting of irinotecan, leucovorin, and 5-fluorouracil. Irinotecan is a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating.
Experimental: Expansion: 2nd Line Colorectal Cancer (CRC) KRAS (+)

2nd Line CRC RAS (+)

RGX-201-01 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: RGX-202-01
RGX-202-01 is a small molecule inhibitor of the creatine transporter, SLC6a8.
Drug: FOLFIRI
FOLFIRI is a chemotherapy regimen consisting of irinotecan, leucovorin, and 5-fluorouracil. Irinotecan is a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating.
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
RGX-202-01 maximum tolerated dose
Time Frame: 6 months
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
Time Frame: 24 months
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
Time Frame: 24 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
RGX-202-01 maximum plasma concentration
Time Frame: 24 months
Pharmacokinetics: Maximum plasma concentration (Cmax) of RGX-202-01.
24 months
RGX-202-01 area under the curve
Time Frame: 24 months
Pharmacokinetics: Area under the curve (AUC) of RGX-202-01.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inspirna, Inc.

Investigators

  • Study Chair: Robert Wasserman, MD, CMO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2018

Primary Completion (Estimated)

December 31, 2023

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

July 13, 2018

First Submitted That Met QC Criteria

July 13, 2018

First Posted (Actual)

July 24, 2018

Study Record Updates

Last Update Posted (Actual)

October 5, 2023

Last Update Submitted That Met QC Criteria

October 4, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RGX-202-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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