MK-1084 + Targeted Therapy for Colorectal Cancer

Recruiting at 67 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Anticancer agents

Disqualifiers: Inflammatory bowel disease, Cardiovascular disease, CNS metastases, 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: 2

Duration: Until discontinuation criteria are met

477 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for colorectal cancer that cannot be surgically removed and involves a specific gene mutation called KRAS G12C. Researchers aim to determine if combining the study drug MK-1084 (an experimental treatment) with cetuximab and the usual chemotherapy helps patients live longer without cancer progression. They also seek to assess the safety and tolerability of this combination. Individuals with advanced colorectal cancer, who have not received prior treatments and possess the KRAS G12C gene mutation, may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients access to 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. However, if you have received prior systemic anticancer therapy within 4 weeks before joining, you may not be eligible. It's best to discuss your specific medications with the trial team.

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

Research has shown that MK-1084, especially when combined with cetuximab, is generally safe and well-tolerated by most people. Some studies found that combining MK-1084 with cetuximab and mFOLFOX6 usually results in few serious side effects.

Cetuximab, a targeted therapy already used for certain cancers, is generally safe. However, all treatments can have side effects. In past studies, common side effects included rash and low magnesium levels, but these are usually manageable.

The combination of MK-1084 and cetuximab is being tested because it targets a specific gene mutation in colorectal cancer. While these treatments seem promising, responses can vary. Those considering joining a trial should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of MK-1084 with cetuximab for colorectal cancer because it introduces a novel approach to treatment. MK-1084 is a new active ingredient that, when paired with cetuximab, targets cancer cells more precisely, potentially enhancing the effectiveness of standard chemotherapy like mFOLFOX6. Unlike the typical regimen, which may include bevacizumab, this combination aims to improve outcomes by leveraging the unique mechanisms of both MK-1084 and cetuximab, offering hope for more effective and targeted therapy.

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

Research has shown that MK-1084, particularly when combined with cetuximab, may effectively treat colorectal cancer with the KRAS G12C mutation. In earlier studies, this combination resulted in a confirmed overall response rate (ORR) of 46%, indicating that nearly half of the patients experienced tumor shrinkage. The disease control rate (DCR), which measures how well the disease is prevented from worsening, was 92%. In this trial, one group of participants will receive MK-1084 and cetuximab alongside standard chemotherapy (mFOLFOX6), potentially managing cancer in more patients. This combination specifically targets the mutation in the cancer cells, potentially increasing its effectiveness for those with this genetic profile. ^{1 2 3 4 5}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced colorectal cancer that can't be removed by surgery and has a specific gene mutation (KRAS G12C). They should not have had previous treatment for this stage of cancer, must have their disease confirmed by lab tests, and if they have HIV or hepatitis B/C, it needs to be under control with medication.

Inclusion Criteria

My HIV is well controlled with medication.

My diagnosis is advanced or spread-out colorectal cancer.

I haven't had systemic anticancer therapy for my advanced colorectal cancer.

Exclusion Criteria

I have a known DPD deficiency.

Has 1 or more conditions that, in the opinion of the investigator, make the participant ineligible for treatment with bevacizumab

I have another cancer that is getting worse or was treated in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-1084, cetuximab, and mFOLFOX6 or mFOLFOX6 with or without bevacizumab until criteria for discontinuation is met

Until discontinuation criteria are met

Every 2 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• MK-1084

Trial Overview The study is testing MK-1084 combined with cetuximab and mFOLFOX6 chemotherapy against the standard treatment which may include mFOLFOX6 alone or with bevacizumab. The goal is to see if adding MK-1084 improves patient outcomes without the cancer growing or spreading.

How Is the Trial Designed?

Group I: MK-1084 + Cetuximab + mFOLFOX6 Experimental Treatment 5 Interventions

Participants will receive MK-1084 orally, cetuximab per label every 2 weeks (Q2W), and mFOLFOX6 chemotherapy: oxaliplatin per label every 2 weeks (Q2W), leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Treatment will continue until criteria for discontinuation is met.

Group II: mFOLFOX6 Active Control 4 Interventions

Participants will receive mFOLFOX6 chemotherapy: oxaliplatin per label Q2W, leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Participants may also receive bevacizumab Q2W at the investigator's discretion. Treatment will continue until criteria for discontinuation is met.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3508

The KRAS G12C inhibitor MK-1084 for ... Results: In arms 1+3, 99 pts, including 53 (54%) with CRC, received MK-1084 alone. In arm 5, 34 pts, including 23 (68%) who had ≥2 prior lines ...

2. merck.com merck.com/news/merck-announces-mk-1084-an-investigational-kras-g12c-inhibitor-shows-antitumor-activity-in-phase-1-trial-of-patients-with-advanced-colorectal-cancer-and-non-small-cell-lung-cancer-whose-tumors-harbo/

Merck Announces MK-1084, an Investigational KRAS ... ... Colorectal Cancer and Non-Small Cell Lung Cancer Whose Tumors Harbor KRAS G12C Mutations ... cancer and these results further demonstrate ...

3. targetedonc.com targetedonc.com/view/mk-1084-regimens-show-promise-in-kras-g12c-mutant-colorectal-cancer

MK-1084 Regimens Show Promise in KRAS G12C–Mutant ... In patients receiving MK-1084 plus cetuximab (Erbitux), the confirmed ORR and DCR were 46% (95% CI, 30%-63%) and 92% (95%, 79%-98%), ...

4. oncodaily.com oncodaily.com/oncolibrary/kandlelit-001-trial

KANDLELIT-001 Trial Demonstrates Promising Activity of ... Efficacy Results​​ MK-1084 + Cetuximab (n=39) improved confirmed ORR to 46% (95% CI: 30–63) and unconfirmed ORR to 56% (95% CI: 40–72), with a ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07209111

NCT07209111 | A Clinical Study of MK-1084 in People ... How many people have the cancer respond (get smaller or go away) to MK-1084 alone or with cetuximab and how these responses compare; About the ...