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 is testing if combining Pembrolizumab and Metformin is more effective for treating advanced melanoma than using Pembrolizumab alone. It targets patients with advanced melanoma that cannot be surgically removed. Pembrolizumab boosts the immune system to fight cancer, and Metformin might help it work better.

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 the combination of Pembrolizumab and Metformin safe for treating melanoma?

Pembrolizumab has been shown to be generally safe in humans, with common side effects including fatigue, rash, itching, and diarrhea. Less common immune-related side effects include thyroid issues, colitis (inflammation of the colon), hepatitis (liver inflammation), and pneumonitis (lung inflammation). ^{1 2 3 4 5}

What makes the drug Pembrolizumab unique for treating melanoma?

Pembrolizumab is unique because it is the first anti-PD-1 therapy approved for melanoma, working by blocking a protein that prevents the immune system from attacking cancer cells, thus allowing the immune system to target and destroy them. It is administered intravenously and has shown significant improvements in survival rates compared to other treatments. ^{1 2 3 5 6}

What data supports the effectiveness of the drug Pembrolizumab for treating melanoma?

Pembrolizumab has shown high durable response rates in a large study of 411 melanoma patients with minimal side effects, and it has been approved for treating advanced melanoma in the US. It has also demonstrated better outcomes compared to another treatment, ipilimumab, in patients with advanced melanoma. ^{3 5 7 8 9}

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 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 (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 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 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]

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 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) 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, 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]

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]

Citations

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

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

Pembrolizumab: first global approval. [2021]

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

Pembrolizumab Utilization and Outcomes for Advanced Melanoma in US Community Oncology Practices. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program. [2018]

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

Pembrolizumab superior to ipilimumab in melanoma. [2017]

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

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

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

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

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

Pembrolizumab in the management of metastatic melanoma. [2020]

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

Pembrolizumab: A Review in Advanced Melanoma. [2022]