Pembrolizumab for Desmoplastic Melanoma

Not currently recruiting at 326 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Brain metastases, Active infection, Autoimmune disease, 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: 50

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of pembrolizumab, an immunotherapy drug, in treating desmoplastic melanoma, a rare type of skin cancer. The trial includes two groups: one for patients whose cancer can be surgically removed and another for those whose cancer cannot be removed. Pembrolizumab may help the immune system attack cancer cells and stop their growth. Patients with this type of melanoma who have not previously received systemic treatment and meet specific health criteria might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people, offering patients a chance to contribute to important advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot receive other cancer treatments or certain medications like systemic corticosteroids within 14 days before joining the trial.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab is generally well-tolerated by people with desmoplastic melanoma. In one study, 89% of patients with melanoma that couldn't be removed by surgery responded to the treatment, with most experiencing tumor shrinkage. About 37% of these patients had a complete response, where their cancer was no longer detectable.

Regarding safety, another study examined the side effects of pembrolizumab and found the treatment to be generally safe, with most side effects being manageable. While some people may experience side effects, they are usually not severe and can often be treated without stopping the medication.

Overall, pembrolizumab has shown promising results in both effectiveness and safety for treating desmoplastic melanoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Researchers are excited about pembrolizumab for desmoplastic melanoma because it leverages the power of immunotherapy. While traditional treatments often involve surgery, chemotherapy, or radiation, pembrolizumab is a monoclonal antibody that enhances the immune system's ability to recognize and destroy cancer cells. This treatment specifically targets the PD-1/PD-L1 pathway, which tumors use to hide from the immune system, making it a promising option for patients with unresectable or advanced forms of the disease. By potentially offering a less invasive and more targeted approach, pembrolizumab could represent a significant advancement in melanoma treatment.

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

Research shows that pembrolizumab effectively treats desmoplastic melanoma, a rare type of skin cancer. Studies have found that 89% of patients experienced a positive response, with tumors either shrinking or disappearing. Notably, 37% of patients saw their tumors completely vanish. This treatment aids the body's immune system in attacking and destroying cancer cells. In this trial, participants in Cohort A will receive pembrolizumab and may undergo surgery if their cancer is potentially resectable. Participants in Cohort B will receive pembrolizumab for unresectable disease. These strong results suggest that pembrolizumab could be a powerful option for people with desmoplastic melanoma, regardless of whether the cancer can be surgically removed. ^{1 4 5 6 7}

Who Is on the Research Team?

Kari L Kendra

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

Adults with desmoplastic melanoma, a type of skin cancer, that can either be surgically removed or not. Participants must not have had prior treatments for this cancer or certain other therapies and drugs recently. They should not have active infections, autoimmune diseases needing recent treatment, or untreated brain metastases. Women who can bear children must test negative for pregnancy and agree to use contraception.

Inclusion Criteria

My medical center will send my samples for a special review.

COHORT B: Treating institution's identity must have current institutional review board approval for this study entered in the system

I haven't needed treatment for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment (Cohort A)

Participants receive pembrolizumab intravenously every 21 days for up to 3 cycles, followed by surgery if disease is resectable

9 weeks

3 visits (in-person)

Treatment (Cohort B)

Participants with unresectable disease receive pembrolizumab intravenously every 21 days for up to 34 cycles

up to 2 years

34 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 12 weeks for the first year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The trial is testing pembrolizumab's effectiveness on resectable (can be removed by surgery) and unresectable (cannot be removed by surgery) desmoplastic melanoma. Pembrolizumab is an immunotherapy drug designed to help the immune system fight cancer cells. The study includes imaging tests like CT scans and may involve biopsies and collecting tissue samples.

How Is the Trial Designed?

Group I: Cohort B (pembrolizumab) Experimental Treatment 6 Interventions

Patients with unresectable disease receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity. Patients undergo CT scan and may undergo PET and MRI throughout the study. Patients also undergo blood sample collection at screening and tumor biopsy throughout the study.

Group II: Cohort A (pembrolizumab, surgery) Experimental Treatment 7 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab. Patients undergo CT scan and may undergo PET and MRI throughout the study. Patients also undergo blood sample collection at screening and tumor biopsy throughout the 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 (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]

In a study of 183 patients with advanced melanoma treated with pembrolizumab, several baseline factors such as active brain metastases, higher total metabolic tumor volume (TMTV), and lower absolute lymphocyte count (ALC) were linked to worse survival outcomes.

TMTV was identified as a more effective predictor of treatment futility compared to other markers like C-reactive protein (CRP) and lactate dehydrogenase (LDH), suggesting that patients with high TMTV may not benefit from pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab. Awada, G., Jansen, Y., Schwarze, JK., et al.[2021]

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 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, 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]

This study presents the first known case of a patient with metastatic melanoma who was successfully treated with pembrolizumab while undergoing hemodialysis, highlighting its potential efficacy in patients with end-stage renal disease.

Pembrolizumab, an FDA-approved monoclonal antibody for metastatic melanoma and non-small cell lung cancer, shows promise for use in patients with renal complications, although specific dosing guidelines for such patients are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. Chang, R., Shirai, K.[2019]

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]

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]

Citations

1.

targetedonc.com

targetedonc.com/view/pembrolizumab-hits-nearly-90-response-rate-in-desmoplastic-melanoma

Pembrolizumab Hits Nearly 90% Response Rate in ...

Pembrolizumab showed an 89% objective response rate in unresectable desmoplastic melanoma, with a 37% complete response rate. The 3-year ...

2.

moffitt.org

moffitt.org/endeavor/archive/single-drug-immunotherapy-shows-success-in-rare-skin-cancer/

Single-Drug Immunotherapy Shows Success in Rare Skin ...

Pembrolizumab delivers 89% response rate in desmoplastic melanoma, sparing patients from harsher combination treatments.

3.

immunopaedia.org.za

immunopaedia.org.za/breaking-news/pembrolizumab-shows-exceptional-efficacy-in-advanced-desmoplastic-melanoma/

Pembrolizumab Shows Exceptional Efficacy in Advanced ...

Pembrolizumab Shows Exceptional Efficacy in Advanced Desmoplastic Melanoma · 37% complete response (CR) – full tumour disappearance. · 89% overall response rate ( ...

4.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2023/pembrolizumab-alone-desmoplastic-melanoma

Pembrolizumab Alone to Treat Desmoplastic Melanoma

In that study, pembrolizumab or nivolumab alone shrank tumors in 38 of 56 (68%) patients, and 19 patients (32%) had complete responses.

5.

uclahealth.org

uclahealth.org/news/release/immunotherapy-helps-extend-lives-patients-with-rare-form

Immunotherapy helps extend the lives of patients with rare ...

The team found that 37% of patients had a complete response, meaning their tumors completely disappeared. Overall, 89% of patients experienced ...

6.

ascopubs.org

ascopubs.org/doi/10.1200/EDBK-25-472752

Management of Cutaneous Melanoma, With a Special ...

The 3-year melanoma specific survival was 96% (Table 1). There was no statistical difference in the benefit of neoadjuvant pembrolizumab between ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12419231/

Anti-PD-1 therapy in unresectable desmoplastic melanoma

Secondary endpoints included progression-free survival (PFS), overall survival (OS) and evaluation of safety and tolerability of pembrolizumab ...