Pembrolizumab/Vibostolimab vs. Pembrolizumab for Melanoma

No longer recruiting at 243 trial locations

Overseen By Toll Free Number

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Steroids, Immunosuppressants, Live vaccines, others

Disqualifiers: Ocular melanoma, Immunodeficiency, CNS metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 17

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new drug combination, pembrolizumab/vibostolimab, can help people with high-risk melanoma live longer without the disease returning, compared to using pembrolizumab alone. Melanoma is a type of skin cancer that can spread quickly if not treated. The trial seeks participants who have undergone surgery for their melanoma but have not received other treatments, except surgery, and who have Stage IIB, IIC, III, or IV melanoma. Candidates should have had surgery no more than 12 weeks ago and should not have specific types of melanoma, such as ocular (eye-related) or mucosal melanoma. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking 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. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust it before starting the trial.

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

Research shows that patients generally tolerate the combination of pembrolizumab and vibostolimab well. In earlier studies involving patients with various cancers, such as non-small cell lung cancer, the treatment demonstrated promising results and proved safe for most individuals, with few experiencing serious side effects.

Pembrolizumab alone has already received approval for treating various cancers, including melanoma, indicating its safety for use in people. While all medications can cause side effects, pembrolizumab is well-researched, and serious reactions are uncommon.

Overall, past research has shown that both treatments in this study—pembrolizumab alone and in combination with vibostolimab—are safe and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab/vibostolimab for melanoma because it combines two active ingredients, pembrolizumab and vibostolimab, which may enhance the immune response against cancer cells. Unlike standard treatments that primarily use pembrolizumab alone, this coformulation targets two different pathways, potentially boosting the body's ability to fight the tumor more effectively. This dual-action approach could offer a more powerful treatment option for patients, possibly improving outcomes compared to current therapies.

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

In this trial, participants will receive either pembrolizumab alone or a combination of pembrolizumab and vibostolimab. Research shows that pembrolizumab effectively treats melanoma by helping the immune system find and attack cancer cells, and studies have demonstrated that it can improve survival rates in patients with melanoma.

The combination of pembrolizumab and vibostolimab is newer, and early research suggests it might enhance the immune system more than pembrolizumab alone. However, the KeyVibe-010 trial for this combination was stopped, indicating mixed results in its development for high-risk melanoma. More data is needed to confirm if it is more effective than pembrolizumab alone. ^{1 2 3 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 people with high-risk Stage IIB, IIC, III or IV melanoma that's been surgically removed. They shouldn't have had other systemic treatments for melanoma and no major surgeries or live vaccines within a month before the trial. Those with HIV must be on effective treatment, and hepatitis B or C patients need controlled viral loads.

Inclusion Criteria

My HIV is well controlled with medication.

I have only had surgery for my melanoma, no other treatments.

I am HBsAg positive but have been on HBV therapy for 4 weeks with an undetectable viral load.

Exclusion Criteria

I have been treated for an autoimmune disease in the last 2 years.

I have received an organ or tissue transplant from another person.

Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab/vibostolimab or pembrolizumab via IV infusion every 3 weeks for up to 17 cycles (approximately 1 year)

12 months

17 visits (in-person)

Follow-up

Participants are monitored for recurrence-free survival and adverse events

13 months

Long-term follow-up

Participants are monitored for overall survival, distant metastasis-free survival, and quality of life changes

Up to approximately 98 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Pembrolizumab/Vibostolimab

Trial Overview The study is testing if combining Pembrolizumab/Vibostolimab improves recurrence-free survival compared to just Pembrolizumab in participants who've had high-risk melanoma surgically removed. The goal is to see which treatment better prevents cancer from coming back.

How Is the Trial Designed?

Group I: Pembrolizumab/Vibostolimab Experimental Treatment 1 Intervention

Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 17 cycles (up to \~1 year).

Group II: Pembrolizumab Active Control 1 Intervention

Participants receive 200 mg pembrolizumab via IV infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 17 cycles (up to \~1 year).

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?

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

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

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]

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 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]

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]

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]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

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 long-term safety analysis of pembrolizumab involving 1567 melanoma patients over a median follow-up of 42.4 months, most adverse events were mild to moderate, with serious treatment-related adverse events occurring in 17.7% of patients, and only two deaths attributed to the drug.

The efficacy of pembrolizumab remained consistent regardless of the occurrence of immune-mediated adverse events or the use of systemic corticosteroids, indicating that these factors did not significantly impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma. Robert, C., Hwu, WJ., Hamid, O., 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05665595

NCT05665595 | A Study of Adjuvant Pembrolizumab ... The primary purpose of this study is to compare pembrolizumab/vibostolimab to pembrolizumab with respect to recurrence-free survival (RFS).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11497960/

The KEYVIBE program: vibostolimab and pembrolizumab ... The KEYVIBE program consists of nine trials that will evaluate the safety and efficacy of vibostolimab monotherapy and vibostolimab-based combination therapy ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS9611

KEYVIBE-010: Adjuvant coformulated vibostolimab with ... The randomized, double-blind, phase 3 KEYVIBE-010 study (NCT05665595) is designed to evaluate the efficacy and safety of adjuvant coformulated vibostolimab and ...

4. merck.com merck.com/news/merck-provides-update-on-phase-3-keyvibe-010-trial-evaluating-an-investigational-coformulation-of-vibostolimab-and-pembrolizumab-as-adjuvant-treatment-for-patients-with-resected-high-risk-melanoma/

Merck Provides Update on Phase 3 KeyVibe-010 Trial ... Merck has an extensive clinical development program evaluating the safety and efficacy of the vibostolimab and pembrolizumab coformulation alone ...

5. onclive.com onclive.com/view/merck-discontinues-keyvibe-010-trial-of-vibostolimab-pembrolizumab-in-resected-high-risk-melanoma

Merck Discontinues KeyVibe-010 Trial of Vibostolimab ... The phase 3 KeyVibe-010 trial of adjuvant vibostolimab plus pembrolizumab in patients with resected high-risk melanoma has been discontinued.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02088

A Study of Adjuvant Pembrolizumab/Vibostolimab (MK ... The primary purpose of this study is to compare pembrolizumab/vibostolimab to pembrolizumab with respect to recurrence-free survival (RFS).

7. esmo.org esmo.org/oncology-news/manageable-safety-and-promising-activity-of-neoadjuvant-pembrolizumab-plus-vibostolimab-pembrolizumab-plus-gebasaxturev-and-pembrolizumab-monotherapy-in-stage-iiib-d-melanoma

Manageable Safety and Promising Activity of Neoadjuvant ... In the article published in the Nature Medicine, the study team reported the primary analysis of safety and antitumour activity in the ...