Pembrolizumab + Metformin for Melanoma

Overseen By Yana Najjar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yana Najjar

Must not be taking: Hypoglycemics, Steroids, Immunosuppressants, others

Disqualifiers: Diabetes, Immunodeficiency, Active infection, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for advanced melanoma, a type of skin cancer difficult to remove with surgery. It combines Pembrolizumab, an existing cancer drug, with Metformin, commonly used for diabetes, to determine if they work better together. Researchers aim to find out if this combination is safe and more effective than Pembrolizumab alone. People with melanoma that can't be surgically removed or has spread might be good candidates, especially if they've previously received other treatments.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on metformin or certain diabetes medications. 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 pembrolizumab is already approved to treat several types of cancer, including melanoma. Most people tolerate it well, but some have experienced side effects like tiredness, nausea, and skin issues.

Metformin, typically used for diabetes, is now being tested for cancer treatment, such as melanoma. Early results suggest it does not worsen outcomes for some cancer types. However, more research is needed to fully understand its safety for cancer patients.

When used together, pembrolizumab and metformin have shown promise in early studies. As this is an early-stage trial, researchers are still learning about their complete safety. Prospective participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and metformin for melanoma because it introduces a fresh approach by pairing an immune checkpoint inhibitor with a common diabetes medication. Pembrolizumab (Keytruda) is already known for its role in boosting the immune system to attack cancer cells, but when combined with metformin, it could potentially enhance the immune response even further. Metformin, typically used for diabetes, may influence the tumor environment, making it more susceptible to immune attack. This combination could offer a more robust treatment option compared to pembrolizumab alone, which is significant given the aggressive nature of melanoma.

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

Research has shown that using Pembrolizumab with Metformin yields promising results for treating melanoma, a type of skin cancer. In this trial, some participants will receive this combination. Earlier studies found that patients receiving both drugs had a 44% lower chance of cancer recurrence or death. Additional research indicates that this combination helps control the disease more effectively and extends patient survival. Pembrolizumab, which participants in this trial may receive, is already effective against advanced melanoma, and Metformin may enhance its efficacy by boosting the immune system. These findings suggest that using both drugs together could be a strong approach to fighting melanoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Yana Najjar, Md

Principal Investigator

Universtiy of Pittsburgh

Are You a Good Fit for This Trial?

Adults with advanced melanoma (stage III or IV) who can provide consent and have measurable disease are eligible for this trial. They must be willing to undergo a biopsy, may be new to immunotherapy or on stable anti-PD-1 therapy, and should not have active brain metastases or diabetes requiring medication. Participants need proper organ function and cannot be pregnant, breastfeeding, or planning pregnancy.

Inclusion Criteria

I have previously received certain immune or targeted therapies.

My organ functions are within normal ranges as per recent tests.

I have recovered from radiation therapy without significant side effects.

Exclusion Criteria

I have had pneumonitis treated with steroids or have it now.

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

I have been diagnosed with HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab alone or in combination with metformin. Pembrolizumab is administered every three weeks, with possible adjustment to every six weeks, for up to two years. Metformin is administered twice daily for nine weeks.

Up to 2 years

Every 3 weeks, with possible adjustment to every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment through standard of care visits, phone calls, or medical records review.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Metformin
• Pembrolizumab

Trial Overview

The study is testing the effectiveness of Pembrolizumab (Keytruda), an existing cancer drug, in combination with Metformin versus using Pembrolizumab alone. The goal is to see if adding Metformin improves treatment outcomes for those with advanced melanoma.

How Is the Trial Designed?

Group I: Pembrolizumab and Metformin Combination Experimental Treatment 2 Interventions

Pembrolizumab (Keytruda), 200mg, by IV, every three weeks, for up to 2 years will be taken in combination with Metformin, 500mg, twice a day, for nine weeks; after the first three doses, pembrolizumab dosing can be changed to 400mg IV every 6 weeks, at the treating physician's discretion.

Group II: Pembrolizumab Active Control 1 Intervention

Pembrolizumab (Keytruda), 200 mg, by IV, every three weeks, for up to 2 years; after the first three doses, dosing can be changed to 400mg IV every 6 weeks, at the treating physician's discretion.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Yana Najjar

Lead Sponsor

Trials

7

Recruited

200+

Merck Sharp & Dohme LLC

Industry 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

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 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 an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

In a study of 168 patients with advanced melanoma treated with pembrolizumab in community oncology settings, the median overall survival was 19.4 months, indicating its effectiveness in real-world scenarios.

Treatment-related toxicity led to discontinuation in 25% of patients, highlighting the importance of monitoring side effects, although the safety profile of pembrolizumab aligns with clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Utilization and Outcomes for Advanced Melanoma in US Community Oncology Practices. Cowey, CL., Liu, FX., Black-Shinn, J., et al.[2021]

In a randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

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]

In a study of 67 advanced melanoma patients treated with pembrolizumab, the drug demonstrated a 27% overall response rate, with 6.5% achieving complete responses, indicating its efficacy even in heavily pretreated patients.

The median overall survival for cutaneous melanoma patients was 14 months, with an 18-month survival rate of 47.1%, and importantly, there were no serious adverse events reported, highlighting the safety of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program. González-Cao, M., Arance, A., Piulats, JM., et al.[2018]

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