What side effects are associated with this type of intervention?

Common treatments for melanoma, such as immune checkpoint inhibitors like Pembrolizumab, can cause side effects including fatigue, rash, diarrhea, and immune-related adverse events like colitis, hepatitis, and endocrinopathies. These treatments may also lead to skin toxicities such as vitiligo and alopecia. Metformin, while primarily used for diabetes, is being studied for its potential anti-cancer effects and can cause gastrointestinal issues like nausea, vomiting, and diarrhea. Combining these treatments may result in a range of side effects from both drug classes, necessitating careful monitoring and management.

What prior FDA approvals exist?

Pembrolizumab, an immune checkpoint inhibitor targeting the PD-1 receptor, has been FDA-approved for the treatment of advanced melanoma. It has shown efficacy both as a monotherapy and in combination with other agents like ipilimumab, another immune checkpoint inhibitor targeting CTLA-4. The combination of nivolumab (another PD-1 inhibitor) and ipilimumab has also been approved for melanoma, demonstrating higher response rates compared to monotherapy. These approvals highlight the effectiveness of targeting immune checkpoints in melanoma treatment.

What other types of research exist?

Promising novel alternatives for melanoma treatment in 2024 include: 1) Nivolumab plus Ipilimumab, which has shown overall survival benefits and high response rates in advanced melanoma. 2) Combination therapy with BRAF inhibitors (e.g., Vemurafenib) and MEK inhibitors (e.g., Cobimetinib) for patients with BRAF mutations. 3) Talimogene Laherparepvec (T-VEC) combined with immune checkpoint inhibitors like Pembrolizumab, which has shown efficacy in unresectable melanoma. 4) Experimental agents targeting the MET pathway for MET-driven tumors. These alternatives offer different mechanisms of action and have demonstrated promising results in clinical settings.

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Monoclonal Antibodies

Pembrolizumab + Metformin for Melanoma

Phase 1

Recruiting

Led By Yana Najjar, Md

Research Sponsored by Yana Najjar

Eligibility Criteria Checklist

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

Must have

Have a performance status of 0, 1 or 2 on the ECOG Performance Scale

Be 18 years of age or older on day of signing informed consent

Must not have

Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Pembrolizumab may cause immune-related side effects such as fatigue, skin reactions, diarrhea, liver inflammation; while Metformin commonly causes digestive issues like stomach pain and nausea. Side effects vary from person to person.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself and am up and about more than 50% of my waking hours.

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I am 18 years old or older.

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My melanoma cannot be removed by surgery or is in an advanced stage.

Exclusion Criteria

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

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

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I have been diagnosed with HIV.

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I have an active tuberculosis infection.

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I am currently on IV antibiotics for an infection.

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I have not received a live vaccine within the last 30 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Ki-67 proliferation index in T cell

Secondary study objectives

Cell cycle status of peripheral blood T lymphocytes by Flow Cytometry

Lymphocyte

Mitochondrial functional restoration in Tumor Infiltrating Lymphocytes by mitochondrial mass

+2 more

Other study objectives

Degree of mitochondrial functional restoration in TIL of patients treated with metformin and pembrolizumab compared to pembrolizumab alone

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Pembrolizumab and Metformin CombinationExperimental Treatment2 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: PembrolizumabActive Control1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab Injection [Keytruda]

2021

Completed Phase 2

~100

Metformin

2006

Completed Phase 4

~2430

0 / 8Eligibility 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

The most common treatments for melanoma include immune checkpoint inhibitors like pembrolizumab and metabolic modulators like metformin. Pembrolizumab blocks the PD-1 receptor on T-cells, enhancing the immune system's ability to detect and destroy cancer cells. Metformin activates AMPK and inhibits mTOR pathways, which can reduce cancer cell growth and improve immune response. These mechanisms are significant for melanoma patients as they provide targeted therapies that can enhance the body's natural defenses against cancer, potentially leading to better treatment outcomes.

Manipulation of Metabolic Pathways and Its Consequences for Anti-Tumor Immunity: A Clinical Perspective.

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Who is running the clinical trial?

Yana NajjarLead Sponsor

5 Previous Clinical Trials

116 Total Patients Enrolled

Merck Sharp & Dohme LLCIndustry Sponsor

4,031 Previous Clinical Trials

5,189,672 Total Patients Enrolled

Yana Najjar, Md5.01 ReviewsPrincipal Investigator - Universtiy of Pittsburgh

University of Pittsburgh

5Patient Review

I've been a patient of Dr Najjar for a couple of years now and have nothing but good things to say. She's an excellent doctor; skilled and compassionate.