MRTX849 + Cetuximab for Colorectal Cancer

Recruiting at 991 trial locations

Overseen By Mirati Therapeutics Study Locator Services

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Mirati Therapeutics Inc.

Must not be taking: KRAS inhibitors, Anti-EGFR

Disqualifiers: Active brain metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 30 months

461 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for patients with colorectal cancer. The treatment combines two drugs that work together to block cancer growth and prevent its spread. One of the drugs has shown promise in treating other types of cancer as well.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination MRTX849 and Cetuximab for colorectal cancer?

Cetuximab, when combined with FOLFIRI, has been shown to improve survival and response rates in patients with metastatic colorectal cancer who have KRAS wild-type tumors. Additionally, cetuximab retreatment has provided clinical benefits for patients who previously responded well to it. ^{1 2 3 4 5}

What safety data exists for the treatment MRTX849 + Cetuximab for colorectal cancer?

Cetuximab, used in combination with other drugs for colorectal cancer, has been associated with skin reactions like rashes and nail changes, which are common but usually manageable. Serious side effects are rare, but some patients may experience severe skin reactions, diarrhea, nausea, or fatigue. Monitoring and managing these side effects are important for patient safety. ^{1 4 6 7 8}

What makes the drug MRTX849 + Cetuximab unique for colorectal cancer?

The combination of MRTX849 (Adagrasib) and Cetuximab is unique because it targets specific genetic mutations in colorectal cancer, such as KRAS mutations, which are not addressed by standard treatments. This approach offers a more personalized treatment option for patients with these specific genetic profiles. ^{1 4 6 9 10}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with advanced colorectal cancer who have the KRAS G12C mutation. They must have had one prior treatment with specific chemotherapy and shown disease progression afterwards. People can't join if they've had brain metastases, previous treatments targeting KRAS G12C, or anti-EGFR antibody therapies.

Inclusion Criteria

My colorectal cancer has a specific KRAS G12C mutation.

My advanced colorectal cancer progressed after first-line chemotherapy.

Exclusion Criteria

I have been treated with an anti-EGFR antibody before.

I have been treated with a drug targeting the KRAS G12C mutation.

I have active cancer spread to my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MRTX849 in combination with cetuximab or chemotherapy

30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Cetuximab
• FOLFIRI Regimen
• mFOLFOX6 Regimen
• MRTX849

Trial Overview The study compares MRTX849 combined with cetuximab to standard chemotherapies (mFOLFOX6 or FOLFIRI) in second-line treatment of colorectal cancer with a specific mutation. It's an open-label trial where patients are randomly assigned to either the new drug combo or standard chemo.

Participant Groups

Group I: MRTX849 + Cetuximab Experimental Treatment 2 Interventions

Group II: mFOLFOX6 or FOLFIRI Active Control 2 Interventions

Cetuximab is already approved in United States, European Union for the following indications:

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

Mirati Therapeutics Inc.

Lead Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

Findings from Research

Cetuximab, a monoclonal antibody targeting the EGFR, has been approved for first-line treatment of KRAS mutation-negative metastatic colorectal cancer (mCRC) in combination with FOLFIRI, showing significant improvements in progression-free survival and overall survival.

The combination of cetuximab with FOLFIRI also resulted in higher objective response rates compared to FOLFIRI alone, making it a valuable treatment option for patients with EGFR-expressing, KRAS wild-type mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

In patients with metastatic colorectal cancer (mCRC) who have KRAS wild-type tumors, adding cetuximab to the FOLFIRI treatment regimen significantly improves overall survival (23.5 months vs. 20.0 months) and progression-free survival (9.9 months vs. 8.4 months).

The study confirmed that KRAS mutation status is a crucial predictive biomarker for the effectiveness of cetuximab, with 37% of tumors showing mutations, while BRAF mutations indicate a poorer prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. Van Cutsem, E., Köhne, CH., Láng, I., et al.[2022]

In a study of 8 patients with recurrent/advanced colorectal cancer, 6 patients showed a positive response to cetuximab, a targeted therapy that binds to epidermal growth factor receptors (EGFR), indicating its efficacy even in later lines of treatment.

Patients receiving cetuximab in combination with CPT-11 had significantly better progression-free survival (7.3 months) and time to treatment failure (9.3 months) compared to those on cetuximab monotherapy (3.0 months and 4.5 months, respectively), highlighting the potential benefits of combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. Katsumoto, Y., Aritake, N., Endoh, A.[2018]

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

In a study involving 65 patients with advanced colorectal cancer who had previously been treated with multiple therapies, the combination of cetuximab and irinotecan showed a response rate of 20% and a median overall survival of 10.4 months, confirming the efficacy of this treatment regimen.

The treatment was associated with low rates of severe toxicity, with only 8% experiencing grade 3 skin toxicity, indicating that cetuximab and irinotecan can be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. Pfeiffer, P., Nielsen, D., Yilmaz, M., et al.[2018]

In a review of clinical trials for colorectal cancer, 76.9% of studies on cetuximab reported dermatologic adverse drug reactions (dADRs), with 50% showing a positive correlation between these reactions and patient survival, indicating that dADRs may be relevant for treatment outcomes.

In contrast, only 42.9% of studies on panitumumab reported dADRs, highlighting significant variability in reporting practices, which limits the ability to assess patient risk and compare the safety profiles of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Completeness in the reporting of dermatologic adverse drug reactions associated with monoclonal antibody epidermal growth factor receptor inhibitors in phase II and III colorectal cancer clinical trials. Bauer, KA., Hammerman, S., Rapoport, B., et al.[2018]

Cetuximab, when combined with irinotecan, can provide patients with metastatic colorectal cancer an additional 1.7 to 2.0 years of life, indicating its efficacy as a treatment option.

However, the cost-effectiveness analysis revealed that the treatment is quite expensive, with costs per life year gained ranging from 205,536 to 323,040 Euros, highlighting the financial considerations of using cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. Norum, J.[2019]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. [2021]

2. Greece pubmed.ncbi.nlm.nih.gov

Cetuximab retreatment in patients with metastatic colorectal cancer who exhibited a clinical benefit in response to prior cetuximab: A retrospective study. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Completeness in the reporting of dermatologic adverse drug reactions associated with monoclonal antibody epidermal growth factor receptor inhibitors in phase II and III colorectal cancer clinical trials. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine and oxaliplatin (CAPOX) plus cetuximab in patients with metastatic colorectal cancer who progressed after oxaliplatin-based chemotherapy. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. [2019]