MRTX849 + Cetuximab for Colorectal Cancer

Not currently recruiting at 1050 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for colorectal cancer in patients with a KRAS G12C mutation. Researchers aim to determine if combining the experimental drug MRTX849 with cetuximab, a targeted therapy, is more effective than standard chemotherapy options like FOLFIRI or mFOLFOX6. It targets individuals whose cancer has progressed after first-line treatment with specific chemotherapy drugs. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to access potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining MRTX849 and cetuximab is promising in terms of safety for patients with challenging cases of colorectal cancer. In earlier studies, most patients tolerated this treatment without major issues.

Adagrasib, another name for MRTX849, demonstrated good results in controlling the disease, whether used alone or with cetuximab. Safety information from these studies suggests that the treatment is manageable for those who have already tried other therapies.

These findings provide some confidence in the treatment's safety. However, as with any new treatment, individual experiences can vary. It's always important to discuss any concerns with a healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Unlike the standard treatments for colorectal cancer, which typically involve chemotherapy regimens like FOLFIRI and mFOLFOX6, the combination of MRTX849 and Cetuximab offers a novel approach by targeting specific genetic mutations. MRTX849 is designed to inhibit the KRAS G12C mutation, a common driver in colorectal cancer, which is not directly targeted by existing chemotherapy options. Researchers are excited about this treatment because it could potentially offer a more precise and effective strategy, especially for patients whose tumors have this specific mutation. This targeted approach may lead to better outcomes with fewer side effects compared to traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

In this trial, participants will receive either the combination of MRTX849 with cetuximab or the standard treatment regimens mFOLFOX6 or FOLFIRI. Previous studies have shown promising results for the combination of MRTX849 with cetuximab in treating colorectal cancer with a specific KRAS G12C mutation. When used together, these drugs improved the overall response rate to 34%, with patients living a median of 15.9 months. These findings suggest that the combination effectively targets cancer cells and offers better outcomes than standard treatments for this mutation type. Additionally, the treatment has proven to be safe and generally well-tolerated by patients, making it a hopeful option for those dealing with this specific type of colorectal cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2212419

Adagrasib with or without Cetuximab in Colorectal Cancer ... In addition, adagrasib monotherapy was associated with a median progression-free survival of 5.6 months and median overall survival of 19.8 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40619745/

Adagrasib in the treatment of colorectal cancer When combined with cetuximab, an anti-EGFR monoclonal antibody, efficacy was further improved with an ORR of 34% and median OS of 15.9 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38587856/

Efficacy and Safety of Adagrasib plus Cetuximab in ... - PubMed Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04793958

NCT04793958 | Phase 3 Study of MRTX849 With ... An open-label, randomized Phase 3 clinical trial comparing the efficacy of MRTX849 administered in combination with cetuximab versus chemotherapy in the second ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.131

Adagrasib (Ada) + cetuximab (Cetux) for KRAS G12C - ... Results: A total of 94 pts received Ada + Cetux. The median number of prior lines of systemic therapy was 3 (range, 1–9); 23 pts (24%) had ...

6. aacrjournals.org aacrjournals.org/cancerdiscovery/article/14/6/982/745540/Efficacy-and-Safety-of-Adagrasib-plus-Cetuximab-in

Efficacy and Safety of Adagrasib plus Cetuximab in Patients ... Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or metastatic KRASG12C- ...