MK-4280A for Colorectal Cancer

No longer recruiting at 193 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: PD-1 inhibitors, PD-L1 inhibitors

Disqualifiers: CNS metastases, Cardiovascular disease, Autoimmune disease, 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: 3

Duration: Up to 27 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MK-4280A, a combination of Favezelimab and Pembrolizumab, for individuals with metastatic colorectal cancer, where the cancer has spread and cannot be surgically removed. The trial aims to determine if MK-4280A is safer and more effective at extending life compared to current treatments, regorafenib and TAS-102. Participants will receive either the experimental treatment or one of the standard treatments. Suitable candidates for this trial have colorectal cancer that has spread, have not responded to other treatments, and can take oral medication. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain cancer therapies or vaccines recently, so it's best to discuss your specific medications with the study team.

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

Research shows that the combination of favezelimab and pembrolizumab has a safety profile similar to that observed in past studies for these drugs. The side effects align with expectations for each drug when used alone. In earlier research, patients tolerated the combination well, and the side effects were generally manageable.

For the standard treatments—regorafenib and TAS-102—these drugs already treat colorectal cancer. Their side effects are well-known, allowing doctors to manage them effectively.

Overall, available data suggests that both the new combination treatment and the standard treatments have safety profiles with known, predictable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for colorectal cancer, which includes treatments like Regorafenib and TAS-102, the combination of Favezelimab and Pembrolizumab is unique because it harnesses the power of the immune system. These drugs are administered together intravenously and work by blocking specific proteins that can suppress the immune response against cancer cells. Researchers are excited about this approach because it has the potential to make the immune system more effective at fighting tumors, offering a new avenue for treatment that could potentially improve patient outcomes compared to traditional therapies.

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

Research shows that combining favezelimab with pembrolizumab, which participants in this trial may receive, may help treat advanced colorectal cancer. Favezelimab targets a protein called LAG-3, which can inhibit the immune system from fighting cancer. Pembrolizumab is already known for aiding the immune system in attacking cancer cells. Studies have found that this combination effectively activates the immune system against tumors. Early results suggest that this treatment might extend patients' lives compared to some standard treatments. In this trial, the standard of care arm includes either regorafenib or TAS-102, chosen by the investigator. The goal of the favezelimab and pembrolizumab combination is to enhance the body's natural defenses to fight cancer more effectively. ^{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 metastatic colorectal cancer that's PD-L1 positive and has worsened after standard treatment. They must be able to take oral meds, have a life expectancy of at least 3 months, and an ECOG score of 0-1 (which means they are fully active or restricted in physically strenuous activity but can do light work).

Inclusion Criteria

My organs are functioning well.

I am fully active or restricted in physically strenuous activity but can do light work.

The patient has a measurable disease according to the RECIST 1.1 guidelines as assessed by the local site investigator.

Exclusion Criteria

I have not had cancer treatment or been in a cancer study in the last 4 weeks.

I have a muscle disorder that causes high levels of creatine kinase.

I have a history of Hepatitis B or an active Hepatitis C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either coformulated favezelimab/pembrolizumab (MK-4280A) intravenously every 3 weeks or standard of care treatment with regorafenib or TAS-102 in 28-day cycles

Up to 27 months

Every 3 weeks for MK-4280A group; every 28 days for standard of care group

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 weeks

Long-term follow-up

Participants are monitored for overall survival and other long-term outcomes

Up to 26 months

What Are the Treatments Tested in This Trial?

Interventions

• Favezelimab
• Pembrolizumab
• Regorafenib
• TAS-102

Trial Overview The study tests MK-4280A, a combo of favezelimab/pembrolizumab, against the usual treatments regorafenib and TAS-102. The goal is to see if MK-4280A helps patients live longer compared to the standard care.

How Is the Trial Designed?

Group I: Favezelimab/Pembrolizumab Experimental Treatment 1 Intervention

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) intravenously (IV) on Day 1, then every 3 weeks (Q3W), for up to 35 infusions.

Group II: Standard of Care (Regorafenib or TAS-102) Active Control 2 Interventions

At the Investigator's choice, participants will receive 160 mg regorafenib orally daily on Days 1-12 of each 28-day cycle or 35 mg/m\^2 TAS-102 orally twice daily on Days 1-5 and Days 8-12 of each 28-day cycle.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05064059

NCT05064059 | A Study of Coformulated Favezelimab/ ... The purpose of this study is to assess the safety and efficacy of coformulated favezelimab/pembrolizumab (MK-4280A) in participants with metastatic colorectal ...

2. merck.com merck.com/news/merck-provides-update-on-phase-3-keyform-007-trial-evaluating-investigational-fixed-dose-combination-of-favezelimab-and-pembrolizumab-for-patients-with-previously-treated-pd-l1-positive-microsatellite/

Merck Provides Update on Phase 3 KEYFORM-007 Trial ... The fixed-dose combination of favezelimab and pembrolizumab (MK-4280A) is being evaluated across multiple solid tumor types and in patients ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9832734/

A first-in-human study of the anti-LAG-3 antibody ... Here, we evaluate the antitumor activity of the LAG-3 antibody favezelimab alone or in combination with pembrolizumab in participants with MSS mCRC.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.LBA248

The phase 3, randomized KEYFORM-007 study. The phase 3 KEYFORM-007 study (NCT05064059) evaluated the efficacy and safety of co-formulated fave/pembro vs standard-of-care (SOC) in PD-L1–positive MSS/pMMR ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00861-4/fulltext

P-81 Phase 3 study of MK4280A (coformulated ... In this ongoing phase 3 study (NCT05064059), we will evaluate the efficacy and safety of MK-4280A in patients with PD-L1–positive pMMR mCRC.