Pre- and Post-Surgery Pembrolizumab for Melanoma

Not currently recruiting at 947 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunotherapy, Biologic therapy

Disqualifiers: Brain metastases, Active infection, Autoimmune, others

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

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

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

Compensation: Varies

Number of Visits: 21

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of pembrolizumab, an immunotherapy, when used before and after surgery for individuals with high-risk melanoma, a type of skin cancer. The goal is to determine if using pembrolizumab both before and after surgery is more effective than using it only after surgery. Participants with stage III or IV melanoma that hasn't spread to the brain and is visible on scans or exams may be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not receive any other biologic therapy, hormonal therapy, or chemotherapy while on the study. 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 shows that pembrolizumab, a treatment for melanoma, is generally safe. Studies have found that it remains safe for long-term use when given alone for advanced melanoma, with serious side effects uncommon for most patients.

The FDA has approved pembrolizumab for treating advanced melanoma, further confirming its safety. In a large study, most participants tolerated pembrolizumab well, indicating that severe problems are rare.

Overall, pembrolizumab's history in treating melanoma suggests it is generally safe for use. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma?

Unlike the standard care for melanoma, which often involves surgery followed by adjuvant treatment, pembrolizumab offers a unique approach by acting as both a neoadjuvant and adjuvant therapy. Pembrolizumab is a type of immunotherapy that works by unleashing the immune system to attack cancer cells, targeting the PD-1 pathway, which is different from traditional treatments like chemotherapy. Researchers are excited about this treatment because it could potentially shrink tumors before surgery, making them easier to remove, and help prevent the cancer from coming back after surgery. This dual approach aims to improve outcomes for patients with melanoma by using the body's own defenses in a more strategic manner.

What evidence suggests that pembrolizumab might be an effective treatment for melanoma?

Research has shown that pembrolizumab can help treat advanced melanoma. In one study, over one-third of patients with advanced melanoma were still alive 10 years after receiving pembrolizumab, outperforming those treated with ipilimumab. Another study found that pembrolizumab halted cancer progression in 43% of patients, compared to 32% with ipilimumab. Additionally, more patients experienced tumor shrinkage with pembrolizumab. In this trial, participants in Arm I will receive adjuvant pembrolizumab, while those in Arm II will receive both adjuvant and neoadjuvant pembrolizumab. The drug is also known to improve long-term survival and reduce the chance of cancer returning or spreading. Overall, pembrolizumab has shown promising results in aiding the body's immune system to fight melanoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Sapna P Patel

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with high-risk melanoma (stage III-IV) that can be removed by surgery. They must not have had previous neoadjuvant immunotherapy or certain other treatments, no active infections, and no history of severe autoimmune disease or pneumonitis. Participants need functioning major organs, no brain metastases, and women of childbearing age must test negative for pregnancy.

Inclusion Criteria

I can have surgery or radiation to remove any tiny cancer remains before starting additional treatment.

I've had radiation or surgery for cancer, and any side effects are now mild.

I have had a brain scan within the last 42 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pembrolizumab IV every 3 weeks for 3 cycles before surgery

9 weeks

3 visits (in-person)

Surgery

Participants undergo surgical resection

Within 3 weeks after neoadjuvant treatment

Adjuvant Treatment

Participants receive pembrolizumab IV every 3 weeks for 15 cycles after surgery

45 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for 2 years, every 6 months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Therapeutic Conventional Surgery

Trial Overview

The study tests the effectiveness of Pembrolizumab, an immune system-boosting drug given before and after surgery versus only after surgery in treating melanoma. It's a phase II trial to see if this approach better prevents cancer from returning.

How Is the Trial Designed?

Group I: Arm I (adjuvant pembrolizumab) Experimental Treatment 5 Interventions

Within 17 days (preferably within 14 days) days after IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood throughout the study and MRI or CT on study.

Group II: Arm II (adjuvant and neoadjuvant pembrolizumab) Active Control 5 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1 every 3 weeks for 3 cycles, then undergo surgery within 3 weeks. Within 84 days, patients receive pembrolizumab IV over 30 minutes every 3 weeks for 15 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood throughout the study and MRI or CT on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

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 (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 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]

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 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In a post hoc analysis of the KEYNOTE-006 study involving 555 patients with advanced melanoma, both ipilimumab and BRAF ± MEK inhibitors showed antitumor activity as subsequent therapies after pembrolizumab, with overall response rates (ORR) of 17.5% for ipilimumab and 30.5% for BRAF ± MEK inhibitors.

Patients who had not previously received BRAF ± MEK inhibitors showed a significantly higher ORR of 43.2% when treated with these agents after pembrolizumab, indicating that prior treatment status may influence the effectiveness of subsequent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. Long, GV., Arance, A., Mortier, L., et al.[2022]

In a phase 3 trial involving 1019 patients with resected high-risk stage III melanoma, pembrolizumab significantly improved distant metastasis-free survival at 3.5 years, with 65.3% of patients in the pembrolizumab group remaining free of distant metastasis compared to 49.4% in the placebo group (HR 0.60).

The study also showed that pembrolizumab led to longer recurrence-free survival, with 59.8% of patients in the pembrolizumab group remaining free of recurrence compared to 41.4% in the placebo group, reinforcing its efficacy as an adjuvant therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Eggermont, AMM., Blank, CU., Mandalà, M., et al.[2021]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10419154/

Efficacy of Pembrolizumab in Advanced Melanoma

The results were comparable to those of nivolumab, showing a 5-year OS of 41% and 43%, respectively, in the two trials [34].

3.

keytruda.com

keytruda.com/melanoma/advanced/

is an fda-approved treatment for advanced melanoma

The cancer did not progress in 43% of people who received KEYTRUDA compared to 32% of people who received ipilimumab. More people saw tumors shrink.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01704287

NCT01704287 | Study of Pembrolizumab (MK-3475) ...

This study was conducted to compare survival using pembrolizumab (SCH 900475, MK-3475) or standard chemotherapy in participants with advanced melanoma (MEL)

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evidence.nejm.org

evidence.nejm.org/doi/full/10.1056/EVIDoa2200214

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The 5-year analysis of adjuvant therapy with pembrolizumab resulted in a sustained improvement in the long-term recurrence- and distant metastasis-free survival

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12454464/

Real-World Outcomes of Pembrolizumab in Advanced ...

Our findings align with clinical trials, demonstrating similar survival outcomes. Younger patients benefited more from pembrolizumab, while ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT01704287

NCT01704287 | Study of Pembrolizumab (MK-3475) ...

This study was conducted to compare survival using pembrolizumab (SCH 900475, MK-3475) or standard chemotherapy in participants with advanced melanoma (MEL)

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sciencedirect.com

sciencedirect.com/science/article/pii/S0959804920313332

Long-term safety of pembrolizumab monotherapy and ...

Results of this large pooled analysis have demonstrated the long-term safety profile of pembrolizumab monotherapy in advanced melanoma.