Pembrolizumab + Other Agents for Melanoma

No longer recruiting at 33 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants

Disqualifiers: Immunodeficiency, CNS metastases, Autoimmune, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for melanoma, a type of skin cancer, to determine if they are safer and more effective than current options. Participants will receive pembrolizumab, a cancer-fighting drug, either alone or with other experimental agents like ATRA (all-trans retinoic acid, a form of vitamin A used in cancer treatment). The study targets patients with Stage III melanoma who require surgery to remove the cancer. Individuals diagnosed with Stage IIIB, IIIC, or IIID melanoma that is untreated and surgically removable may be suitable candidates. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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 be on immunosuppressive therapy or have received systemic anticancer therapy within 4 weeks before starting the study.

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

Research has shown that pembrolizumab is generally safe and well-tolerated, whether used alone or with other drugs. Studies on pembrolizumab with favezelimab indicate a manageable safety profile, with no treatment-related deaths. Similarly, trials with pembrolizumab and vibostolimab have consistently demonstrated an expected and manageable safety profile.

For the combination of pembrolizumab and gebasaxturev, research has also indicated a manageable safety profile. The pairing of pembrolizumab and ATRA (all-trans retinoic acid) is well-tolerated and has shown promise in reducing certain cells that suppress the immune system, potentially enhancing cancer treatment effectiveness. Lastly, studies involving MK-4830 and pembrolizumab have reported some skin reactions but generally maintain a safe profile.

In summary, while each combination treatment has unique features, all have been shown to be well-tolerated in research settings. This information can help potential trial participants feel more informed about the treatments' safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they bring new approaches to tackling melanoma. Unlike traditional therapies that often rely solely on surgery or chemotherapy, these treatments combine pembrolizumab, a well-known checkpoint inhibitor, with other innovative agents. For instance, favezelimab, vibostolimab, and MK-4830 are unique because they target different immune pathways to potentially enhance the body's ability to fight cancer. Gebasaxturev (V937) is administered directly into the tumor, which might boost local immune responses. Meanwhile, ATRA offers a different angle by influencing cell differentiation. These combined approaches could offer enhanced effectiveness by engaging the immune system more robustly than current options.

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

Research shows that pembrolizumab, both alone and with other treatments, holds promise for treating melanoma. In this trial, participants may receive pembrolizumab alone, which earlier studies found helped patients with advanced melanoma live longer, with one-third surviving for ten years. Another arm of this trial will test the combination of pembrolizumab and favezelimab, which previous studies have shown leads to better response rates and more tumor shrinkage than pembrolizumab alone. When combined with vibostolimab, pembrolizumab showed a trend toward better results, with 81% of patients experiencing no major health events after 18 months. The combination of pembrolizumab and gebasaxturev resulted in a 72% rate of event-free survival over the same period. Adding all-trans retinoic acid (ATRA) to pembrolizumab also demonstrated good survival rates and high response rates. Lastly, the combination of pembrolizumab and MK-4830 was well-tolerated and matched the positive survival outcomes seen in other studies. Participants in this trial will be assigned to one of these treatment arms to evaluate the effectiveness and safety of these combinations. ^{3 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 III melanoma suitable for pre-surgery (neoadjuvant) therapy. They must not be pregnant, breastfeeding, or planning to conceive; agree to use contraception; have good organ function; and no recent immunosuppressive treatments or active infections. Prior treatment for melanoma is limited to surgery or radiotherapy on the primary tumor.

Inclusion Criteria

I am not pregnant or breastfeeding, and if I can have children, I use effective birth control or practice abstinence.

My organs are functioning well.

My melanoma diagnosis was confirmed through lab tests.

Exclusion Criteria

I have not had a live vaccine in the last 30 days.

I have an immune system disorder or have been on immune-weakening medication recently.

My cancer has spread to my brain or the membranes around my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive investigational treatments prior to tumor resection surgery

Up to 1 year

Adjuvant Treatment

Participants receive pembrolizumab after surgery

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 16 months

Long-term Follow-up

Participants are monitored for recurrence-free survival

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• ATRA
• Pembrolizumab

Trial Overview The study tests Pembrolizumab alone or combined with other agents (Vibostolimab, Gebasaxturev, MK-4830, Favezelimab, ATRA) in different groups of participants. The aim is to find which combination works better than current treatments by comparing safety and effectiveness before surgery.

How Is the Trial Designed?

Group I: Pembrolizumab + all-trans retinoic acid (ATRA) Experimental Treatment 2 Interventions

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Group II: Pembrolizumab + Vibostolimab Experimental Treatment 2 Interventions

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Group III: Pembrolizumab + MK-4830 Experimental Treatment 2 Interventions

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus MK-4830 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Group IV: Pembrolizumab + Gebasaxturev Experimental Treatment 2 Interventions

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus gebasaxturev (V937) intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Group V: Pembrolizumab Experimental Treatment 1 Intervention

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Group VI: Favezelimab + Pembrolizumab Experimental Treatment 1 Intervention

Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive MK-4280A (favezelimab and pembrolizumab administered as a co-formulation) IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

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

Approved in United States as Tretinoin for:

• Acute promyelocytic leukemia (APL)

Approved in European Union as Tretinoin for:

• Acute promyelocytic leukemia (APL)

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

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) 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]

The combination of all-trans retinoic acid (ATRA) and pembrolizumab was well tolerated in a phase Ib/II trial with 24 patients, establishing a recommended phase II dose of 150 mg/m2 ATRA plus 200 mg pembrolizumab every three weeks.

This treatment showed a high overall response rate of 71%, with 50% of patients achieving a complete response and a median progression-free survival of 20.3 months, indicating its potential as an effective frontline therapy for advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma. Tobin, RP., Cogswell, DT., Cates, VM., et al.[2023]

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 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 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, 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]

Citations

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Estimating efficacy of favezelimab plus pembrolizumab ... Favezelimab plus pembrolizumab had a higher response rate and greater reduction in tumor burden vs pembrolizumab alone. Results suggest ...

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A first-in-human study of the anti-LAG-3 antibody ... Favezelimab plus pembrolizumab vs pembrolizumab improved exploratory efficacy outcomes of survival and duration of response in MSS mCRC.

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Merck Provides Update on KeyVibe and KEYFORM ... Favezelimab is being evaluated as an investigational fixed-dose combination with pembrolizumab in the KEYFORM program. Merck is discontinuing ...

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NCT06036836 | Study of Favezelimab Coformulated With ... The purpose of this study is to evaluate pathologic complete response (pCR) rate of coformulated favezelimab/pembrolizumab (MK-4280A) or pembrolizumab as ...

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256 A Randomized, Double-Blind, Phase 2 Study of ... Early phase studies have also shown promising antitumor activity and manageable safety with favezelimab (anti–LAG3 antibody) + pembrolizumab (pembro; anti‒PD-1 ...