What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, including immunotherapy agents like pembrolizumab, can cause side effects such as fatigue, diarrhea, rash, and immune-related adverse events like pneumonitis, colitis, and hepatitis. Regorafenib is associated with hand-foot skin reactions, hypertension, and liver toxicity, while TAS-102 (trifluridine and tipiracil) can cause neutropenia, anemia, and gastrointestinal symptoms. Fruquintinib, another treatment option, has been reported to cause hypertension, proteinuria, and hand-foot syndrome. Serious adverse events and hospitalization are also possible with these treatments.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of colorectal cancer, particularly for cases with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. Pembrolizumab (Keytruda), an anti-PD-1 antibody, is approved for the treatment of MSI-H or dMMR metastatic colorectal cancer. Nivolumab (Opdivo), another anti-PD-1 antibody, is also approved for similar indications, often in combination with ipilimumab (Yervoy), an anti-CTLA-4 antibody. These treatments are similar to the coformulated favezelimab/pembrolizumab being studied, as they involve immune checkpoint blockade to enhance the body's immune response against cancer cells.

What other types of research exist?

Promising novel alternatives to coformulated favezelimab/pembrolizumab for colorectal cancer patients include: 1) Regorafenib, a multi-kinase inhibitor, which has been used as a standard of care. 2) TAS-102 (trifluridine and tipiracil), an oral combination chemotherapy. 3) Cetuximab, an anti-EGFR antibody, often used in combination with chemotherapy. 4) Enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, which has shown promise in other cancers and is being explored in colorectal cancer. 5) Avelumab, a PD-L1 inhibitor, which has shown some efficacy in other solid tumors and may be considered in clinical trials for colorectal cancer.

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Monoclonal Antibodies

MK-4280A for Colorectal Cancer

Phase 3

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within 10 days prior to first dose of study intervention.

Has a histologically confirmed colorectal adenocarcinoma that is metastatic and unresectable

Must not have

Has neuromuscular disorders associated with an elevated creatine kinase (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)

Has known history of Hepatitis B or known active Hepatitis C virus infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 27 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new combination treatment for patients with advanced colorectal cancer. The treatment aims to boost the immune system's ability to fight cancer more effectively than current options.

Who is the study for?

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).

What is being tested?

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.

What are the potential side effects?

Possible side effects include immune system reactions affecting organs, infusion-related symptoms like fever or chills, fatigue, digestive issues such as nausea or diarrhea, skin reactions, hormonal gland problems (like thyroid dysfunction), and potential increase in infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My colorectal cancer has spread and cannot be surgically removed.

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I can swallow pills and don't have major stomach issues affecting medicine absorption.

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I can provide a recent (within 5 years) tumor sample that hasn't been exposed to radiation.

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I can swallow pills and don't have major stomach issues affecting medicine absorption.

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My condition worsened after standard treatment or I couldn't tolerate it.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have received an organ or tissue transplant from another person.

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I have been treated for an autoimmune disease in the last 2 years.

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I have been treated with specific immune-targeting cancer drugs before.

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I have taken regorafenib or TAS-102 before.

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

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I have or had lung inflammation that needed steroids.

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I have cancer that has spread to my brain or spinal cord.

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I do not have an active infection needing treatment.

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I haven't had serious heart problems in the last year.

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My tumor is identified as having high microsatellite instability.

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I have had pancreatitis before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 27 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 27 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 27 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival (OS)

Secondary study objectives

Change from Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score

Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

Change from Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

+10 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Favezelimab/PembrolizumabExperimental Treatment1 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 Control2 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.

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for colorectal cancer include immune checkpoint inhibitors like pembrolizumab (anti-PD-1) and favezelimab (anti-LAG-3), which work by blocking proteins that inhibit immune responses, thereby enhancing the body's ability to attack cancer cells. This is particularly important for colorectal cancer patients as it can lead to improved overall survival and response rates. Other treatments include chemotherapy agents like regorafenib and TAS-102, which target cancer cell division and DNA synthesis, respectively. These mechanisms are vital as they offer multiple avenues to control and potentially reduce tumor growth.