Phase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer

NCT05722327 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0374NCI-2023-01157
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To find the recommended dose of MRTX849 that can be given in combination with cetuximab and irinotecan to patients with colorectal cancer that have a mutation (genetic change) called KRAS G12C.

Conditions

Colon Cancer; Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

  through study completion; an average of 1 year.

Study Arms (2)

Stage 1 ( MRTX849 and Irinotecan)

EXPERIMENTAL

Participants assigned to Stage 1, participants dose levels of MRTX849 and irinotecan will depend on when the participants joined the study. This study will also test 2 different dosing schedules: concurrent dosing or staggered dosing

Drug: MRTX849; Drug: Irinotecan; Drug: Cetuximab

Stage 2 ( MRTX849 and Irinotecan)

EXPERIMENTAL

Participants assigned to Stage 2 will receive MRTX849 and irinotecan at the dose level that was recommended during Stage 1. This study will also test 2 different dosing schedules: concurrent dosing or staggered dosing

Drug: MRTX849; Drug: Irinotecan; Drug: Cetuximab

Interventions

MRTX849 DRUG

Given by PO (mouth)

Stage 1 ( MRTX849 and Irinotecan); Stage 2 ( MRTX849 and Irinotecan)

Irinotecan DRUG

Given by IV (vein)

Stage 1 ( MRTX849 and Irinotecan); Stage 2 ( MRTX849 and Irinotecan)

Cetuximab DRUG

Given by IV (vein)

Also known as: C225, Erbitux™, MC-C225, MOAB C225

Stage 1 ( MRTX849 and Irinotecan); Stage 2 ( MRTX849 and Irinotecan)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with KRASG12C mutation. KRASG12C on ctDNA may also be used as basis of eligibility, with approval from study or site PIs.
• Unresectable or metastatic disease.
• Previously treated with at least two prior chemotherapy regimens for metastatic disease (where a regimen is defined as a unique combination of 5-FU, oxaliplatin, irinotecan, bevacizumab (or biosimilar), capecitabine). A treatment with adjuvant therapy with progression within 6 months of completing therapy would be considered a prior chemotherapy regimen.
• Presence of tumor lesions to be evaluated per RECIST 1.1patients must have measurable disease.
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of the proposed combination in patients \<18 years of age, and because solid tumor malignancies with KRASG12C mutation is rare among patients \< 18 years of age, children are excluded from this study.
• Able to take oral medications.
• Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or, investigational agent) and radiation therapy discontinued at least 2 weeks before first dose or five half-lives whichever is shorter.
• Recovery from the adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia and prior oxaliplatin-induced neuropathy).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Laboratory values within the screening period:
• Absolute neutrophil count ≥ 1,000/mm3 (≥ 1.0, 109/L)
• Platelet count ≥ 100,000/mm3 (≥ 100, 109/L)
• INR/PTT ≤ 1.5 upper limit of normal (ULN)
• Hemoglobin ≥ 9 g/dL, in the absence of transfusions for at least 2 weeks
• Total bilirubin ≤ 1.5 upper limit of normal (ULN) (if associated with Gilbert's disease or UGT1A1\*28 homozygosity, ≤ 3 ULN)

You may not qualify if:

• Active brain metastases, unless adequately treated and patient is neurologically stable (except for residual symptoms of central nervous system treatment) for at least 2 weeks prior to enrollment without corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
• Prior treatment with KRASG12C inhibitor + EGFR inhibitor combo
• Patients with carcinomatous meningitis.
• History of significant hemoptysis or hemorrhage within 4 weeks of the first dose, unless resolved or stable.
• Major surgery within 4 weeks of first dose.
• History of intestinal disease or major gastric surgery likely to alter absorption of study treatment.
• Any of the following cardiac abnormalities:
• Symptomatic or uncontrolled atrial fibrillation or other arrhythmia
• Unstable angina pectoris or myocardial infarction within the last 6 months.
• Congestive heart failure ≥ NYHA Class 3 within the last 6 months.
• QTc \> 480 milliseconds.
• LVEF, if known, beyond the allowable window for single-agent MRTX849
• Ongoing need for a medication with any of the following characteristics that cannot be switched to alternative treatment prior to study entry (see Appendix 2): known risk of Torsades de Pointes or QT prolongation; substrate of CYP3A with narrow therapeutic index; strong inducer or inhibitor of CYP3A and/or P-gp; strong inhibitor of BCRP; and proton pump inhibitors.
• Known or suspected presence of another malignancy that could be mistaken for the malignancy under study.
• Known human immunodeficiency virus (HIV) seropositivity or active Hepatitis B or C. Patients treated for hepatitis C with no detectable viral load are permitted.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Mirati Therapeutics: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms

Interventions

adagrasib; Irinotecan; Cetuximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David S. Hong, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: February 10, 2023
• Study Start: December 6, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

US (1)