A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations

NCT06412198 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-1002NCI-2024-04127
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

To learn if the drug combination of adagrasib, cetuximab, and cemiplimab can help to control metastatic CRC with KRAS G12C mutations.

Conditions

Metastatic Colorectal Cancer; KRAS G12C Mutations

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (2)

Lead-In

EXPERIMENTAL

Participants enrolled in the Lead-In phase, the dose of adagrasib participants receive will depend on when the participant join this study. The first group of participants will receive the starting dose level of adagrasib. If intolerable side effects are seen, a second group of participants will be enrolled to receive a lower dose. One (1) of these 2 doses will be chosen as the recommended dose of adagrasib.

Drug: Cetuximab; Drug: Cemiplimab; Drug: Adagrasib

Expansion

EXPERIMENTAL

Participants enrolled in the Expansion phase, participants will receive adagrasib at the recommended dose that was found in the Lead-In phase.

Drug: Cetuximab; Drug: Cemiplimab; Drug: Adagrasib

Interventions

Cetuximab DRUG

Given by IV

Also known as: ERBITUX

Expansion; Lead-In

Cemiplimab DRUG

Given by IV

Expansion; Lead-In

Adagrasib DRUG

Given by PO

Expansion; Lead-In

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 advanced/metastatic microsatellite stable colorectal cancer with KRASG12C mutation with 1+ prior line(s) of therapy
• Confirmed KRASG12C mutation status. If a molecular profiling report is not available, a representative paraffin-embedded tumor block or a minimum of 10 unstained slides will be requested for retrospective KRASG12C mutation testing.
• Unresectable or metastatic disease.
• Participants must have received at least one prior line of chemotherapy for metastatic disease with progression on treatment or intolerance to therapy.
• Presence of measurable disease per RECIST 1.1
• Willingness to participate in on-study related procedures, including mandatory biopsies (one baseline and one on-treatment biopsy).
• 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, 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 7 days before first dose.
• Recovery from the treatment-related 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 x 109/L)
• Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
• Hemoglobin ≥ 9 g/dL, in the absence of transfusions for at least 2 weeks

You may not qualify if:

• Prior PD1 or CTLA4 inhibition therapy
• Prior KRASG12C inhibition therapy
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Active brain metastases, unless adequately treated and participant 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)
• Ongoing need for a medication with any of the following characteristics that cannot be switched to alternative treatment within 10 days prior to study entry: known risk of QTc prolongation or Torsades de Pointes; substrate of CYP3A with a narrow therapeutic index; strong inducer or inhibitor of CYP3A and/or P-gp; strong inhibitor of BCRP; strong inhibitor or inducer of CYP2C19; and proton pump inhibitors
• Major surgery within 4 weeks of the first dose of any study drug
• History of intestinal disease or major gastric surgery likely to alter absorption of study treatment (to be determined by the treating physician)
• Pregnancy. Women of child-bearing potential must have a negative serum or urine pregnancy test during screening
• Breast-feeding or planning to breast feed during the study or within 6 months after end of treatment.
• Participants with symptomatic leptomeningeal disease.
• Major surgery within 4 weeks of first dose of any study drug.
• History of intestinal disease or major gastric surgery likely to alter absorption of study treatment, to be determined by the treating physician
• Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B (HBV) or C (HCV) infection as tested in a CLIA certified lab using a positive HIV antibody test. For Hepatitis B and C, an antigen that is drawn and positive. Note that the following are permitted:
• Participants treated for HIV with no detectable viral load on current regimen for at least 1 month prior to randomization;

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; cemiplimab; adagrasib

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)

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

Study Officials

• Christine Parseghian, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine Parseghian, MD

CONTACT

(713) 792-2828; GIClinicalTrials@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: May 9, 2024
• First Posted: May 14, 2024
• Study Start: August 28, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

US (2)