Pembrolizumab/Quavonlimab for Advanced Colorectal Cancer

Recruiting at 112 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

302 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Pembrolizumab/Quavonlimab for treating advanced colorectal cancer?

Pembrolizumab, a part of the treatment, has shown effectiveness in treating various cancers like non-small cell lung cancer and melanoma by helping the immune system attack cancer cells. Additionally, the combination of pembrolizumab with other drugs like quavonlimab and vibostolimab has shown promise in treating solid tumors. ^{1 2 3 4 5}

Is pembrolizumab generally safe for human use?

Pembrolizumab, also known as KEYTRUDA, has been used in various clinical trials for conditions like melanoma and lung cancer. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects can include lung inflammation (pneumonitis), liver inflammation (hepatitis), and thyroid issues. Despite these risks, the benefits in treating life-threatening conditions have been considered to outweigh the potential side effects. ^{1 2 6 7 8}

What makes the drug Pembrolizumab/Quavonlimab unique for advanced colorectal cancer?

Pembrolizumab/Quavonlimab is unique because it combines pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, with quavonlimab, potentially enhancing the immune response against advanced colorectal cancer, especially in cases where the cancer expresses PD-L1, which is associated with a poor prognosis. ^{1 2 9 10 11}

What is the purpose of this trial?

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 dMMR Metastatic Stage IV Colorectal Cancer.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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) 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab Every 6 Weeks Versus Every 3 Weeks in Advanced Non-Small Cell Lung Cancer. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. [2022]