Pembrolizumab/Quavonlimab for Advanced Colorectal Cancer

Not currently recruiting at 144 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active CNS metastases, Autoimmune, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of several new combinations of cancer medications for individuals with advanced colorectal cancer that has specific genetic features (MSI-H or dMMR) and has metastasized. The study compares different treatments, all involving pembrolizumab (an immunotherapy drug), to determine which is most effective. Individuals who have either tried other standard treatments for advanced colorectal cancer without success or have not yet received any treatment for this stage might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like systemic steroids or have had recent chemotherapy, radiotherapy, or investigational treatments.

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

Research has shown that pembrolizumab, whether used alone or with other drugs, is generally well-tolerated. In studies, when combined with MK-4830, the side effects were manageable, with most being mild to moderate.

Early studies on the pembrolizumab/quavonlimab combination suggest a similar safety profile, showing promise in treating various cancers with a reasonable safety record.

The combination of favezelimab and pembrolizumab produced expected side effects based on past results from each drug alone, with no new safety concerns.

Trials of pembrolizumab with vibostolimab reported generally manageable side effects within an acceptable range for patients.

Overall, these treatments have been studied enough to suggest they are generally safe, though side effects can occur. Discuss any concerns with the trial team or a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced colorectal cancer because they offer several innovative approaches. Pembrolizumab, a well-established immunotherapy, is being combined with novel agents like Quavonlimab, Favezelimab, Vibostolimab, and MK-4830, each enhancing the immune response in unique ways. Quavonlimab, for instance, is a CTLA-4 inhibitor, which can potentially boost T-cell activation more effectively than traditional therapies. Favezelimab targets the LAG-3 pathway, another immune checkpoint, offering a fresh angle for combating cancer cells. Meanwhile, MK-4830 specifically targets macrophages within tumors, potentially reducing their ability to suppress immune activity. These combinations could provide a more comprehensive attack on cancer cells compared to existing options like chemotherapy or standalone immunotherapies.

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

Research has shown that pembrolizumab, often used with other drugs, has potential in treating certain cancers. In this trial, participants may receive pembrolizumab with MK-4830, which studies indicate is safe and may effectively target specific cancer cell pathways. Another arm of this trial involves pembrolizumab with quavonlimab, which early studies have shown to have promising anti-tumor effects. Although trials of pembrolizumab with favezelimab did not show a survival benefit in a slightly different setting, it is being tested in this trial for its potential effects. Additionally, pembrolizumab with vibostolimab has demonstrated lasting anti-tumor effects in other cancers, suggesting it might also help with colorectal cancer. Each combination in this trial aims to help the immune system fight cancer more effectively. ^{1 4 5 6 7}

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 Stage IV colorectal cancer that's either MSI-H or dMMR. They should have measurable disease, adequate organ function, and a life expectancy of at least 3 months. Women must not be pregnant/breastfeeding and use effective contraception if of childbearing potential. Excluded are those with recent treatments/surgeries, live vaccines, other cancers within 2 years, CNS metastases, severe drug hypersensitivity, active infections like HIV/Hepatitis B/C, certain heart diseases or conditions that could affect study participation.

Inclusion Criteria

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

I have been treated with specific chemotherapy drugs for my condition.

I have left-sided, RAS wild-type cancer and received EGFR therapy.

Exclusion Criteria

I had radiotherapy less than 2 weeks before starting the study treatment.

I am currently being treated for an active infection.

I have had pancreatitis before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various treatments including pembrolizumab, quavonlimab, and other combinations for up to approximately 2 years

Up to 104 weeks

Every 3 to 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 50 months

What Are the Treatments Tested in This Trial?

Interventions

• MK-4830
• Pembrolizumab
• Pembrolizumab/Favezelimab
• Pembrolizumab/Quavonlimab
• Pembrolizumab/Vibostolimab

Trial Overview The trial tests the effectiveness and safety of a combined treatment (pembrolizumab/quavonlimab) against other therapies in patients with advanced colorectal cancer characterized by MSI-H/dMMR. It compares this combination to pembrolizumab alone or with favezelimab/vibostolimab/MK-4830 to see which works best.

How Is the Trial Designed?

Group I: Pembrolizumab/Vibostolimab Experimental Treatment 1 Intervention

Participants receive co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years.

Group II: Pembrolizumab/Quavonlimab Experimental Treatment 1 Intervention

Participants receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years.

Group III: Pembrolizumab/Favezelimab Experimental Treatment 1 Intervention

Participants receive co-formulated pembrolizumab/favezelimab (200 mg/800 mg) every 3 weeks (Q3W) for up to approximately 2 years.

Group IV: Pembrolizumab Plus MK-4830 Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.

Group V: Pembrolizumab Active Control 1 Intervention

Participants receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years.

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

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

In a study of 277 melanoma patients treated with pembrolizumab, the six-weekly (Q6W) infusion schedule showed similar safety profiles to the three-weekly (Q3W) schedule, with comparable rates of severe adverse events (14.9% for Q6W vs. 15.5% for Q3W).

The estimated 12-month recurrence-free survival was slightly higher for the Q6W group (78.9%) compared to the Q3W group (74.2%), suggesting that Q6W is an effective alternative that can help reduce healthcare resource use without compromising patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma. Mehta, I., Dayimu, A., Kumar, S., et al.[2023]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

Citations

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KEYSTEP-008: Phase II Trial of Pembrolizumab-Based ... The results from this study will help define the role of combination therapy in this subset of patients with a poor prognosis. Executive summary. Metastatic ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS3639

Phase 2 study of pembrolizumab-based combination ... This ongoing, open-label, multicenter, multiarm, randomized, phase 2 trial (NCT04895722) will evaluate efficacy and safety of coformulated pembro and anti–CTLA ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12453052/

Targeting ILT4 to Improve Immunotherapy Efficacy in Solid ... In terms of toxicity, both MK-4830 monotherapy and in combination with pembrolizumab showed acceptable safety in the dose range of 3–1600 mg Q3W ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/28/1/57/675028/First-in-Class-Anti-immunoglobulin-like-Transcript

First-in-Class Anti-immunoglobulin–like Transcript 4 Myeloid ... Here, we report efficacy and safety data from the first-in-human phase I trial of MK-4830 as monotherapy and in combination with pembrolizumab in patients with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04895722

Study Details | NCT04895722 | Evaluation of Co- ... The purpose of this study is to assess the efficacy and safety of co-formulated pembrolizumab/quavonlimab versus other treatments in participants with MSI-H or ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37701986/

KEYSTEP-008: phase II trial of pembrolizumab-based ... The open-label, randomized, phase II KEYSTEP-008 trial, which will evaluate the efficacy and safety of pembrolizumab-based combination therapy.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03564691

NCT03564691 | Study of MK-4830 as Monotherapy and in ... Dose escalation will proceed based on emerging safety and tolerability data of MK-4830 as monotherapy (Part A and B) and as combination therapy with ...