Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT06369259

Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer

Led by M.D. Anderson Cancer Center · Updated on 2026-04-01

33

Participants Needed

1

Research Sites

205 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

To learn if avutometinib in combination with defactinib and cetuximab can help to control unresectable, anti-EGFR-refractory, advanced colorectal cancer.

CONDITIONS

Official Title

Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Signed informed consent before screening
  • Age 18 years or older at consent
  • Confirmed adenocarcinoma of colon or rectum with unresectable or metastatic disease measurable by RECIST 1.1
  • Tumor or circulating DNA shows wild-type KRAS, NRAS, EGFR ectodomain, and BRAF V600E at diagnosis
  • Prior systemic chemotherapy for metastatic colorectal cancer or progression within 6 months of adjuvant chemotherapy
  • Prior anti-EGFR therapy (cetuximab or panitumumab) for at least 16 weeks with complete or partial response before progression
  • ECOG performance status 0 or 1
  • Recovery from acute chemotherapy effects except alopecia or grade 2 peripheral neuropathy; at least 21-day washout from chemotherapy
  • Recovery from radiotherapy side effects; at least 7-day washout from radiotherapy
  • Adequate blood counts: ANC ≥ 1.5 x 10^9/L, Hemoglobin ≥ 9 g/dL, Platelets ≥ 100 x 10^9/L
  • Adequate liver function: ALT and AST ≤ 3 x ULN or ≤ 5 x ULN if liver metastases; bilirubin ≤ 1.5 x ULN and < 1.5 mg/dL
  • Adequate kidney function: Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL/min
  • QTc interval ≤ 480 ms
  • Ability to take oral medications
  • If sexually active female of childbearing potential, negative pregnancy test and effective contraception
  • Willingness and ability to participate and comply with trial requirements
  • Prior or concurrent malignancies allowed if not interfering with safety or efficacy
Not Eligible

You will not qualify if you...

  • History of severe allergic reaction or intolerance to cetuximab or panitumumab
  • Allergies to compounds similar to cetuximab or history of red meat allergy/tick bite
  • Prior treatment with ERK1/2, MEK, or BRAF inhibitors
  • Symptomatic brain metastases
  • Known leptomeningeal disease
  • History or risk of retinal vein occlusion or central serous retinopathy
  • Other malignancies within 3 years except certain treated skin, bladder, prostate, cervical, or indolent cancers
  • Significant cardiovascular diseases including recent acute coronary syndromes, symptomatic heart failure, serious arrhythmias, uncontrolled hypertension
  • Active systemic bacterial or fungal infection requiring IV treatment
  • Active HIV infection requiring therapy
  • Active hepatitis B or C infection as defined
  • Impaired gastrointestinal function affecting drug absorption
  • Any other condition judged unsafe or interfering with study participation
  • Major surgery within 6 weeks or incomplete recovery from surgery side effects
  • Systemic anti-cancer therapy within 4 weeks or within 5 half-lives of prior drug
  • Pregnant or nursing women
  • History of rhabdomyolysis
  • Medical, psychiatric, or cognitive conditions compromising consent or protocol compliance

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

MD Anderson Cancer Center

Houston, Texas, United States, 77807

Actively Recruiting

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Research Team

C

Christine Parseghian, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

2

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