Pembrolizumab for Merkel Cell Carcinoma

(MCC Trial)

Overseen By Lydia Giles, BSN, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Must be taking: HBV antivirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Unresectable disease, Active infection, 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: 10

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of pembrolizumab, a type of immunotherapy, in treating Merkel cell carcinoma, a rare and aggressive skin cancer. The goal is to determine if pembrolizumab can reduce cancer recurrence when administered before and after surgery. Researchers aim to understand any potential side effects. Individuals with resectable stage I-III Merkel cell carcinoma, who have sufficient tumor tissue for biopsy, may qualify for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 systemic anti-cancer therapy, immunosuppressive therapy, or have received a live vaccine recently, you may need to stop or adjust those treatments before joining the trial.

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

Research shows that pembrolizumab is generally well-tolerated by patients with Merkel cell carcinoma. A review of 31 clinical trials found that pembrolizumab is consistently safe across different uses. In patients with advanced Merkel cell carcinoma, pembrolizumab has shown encouraging survival rates and manageable side effects.

While some patients may experience side effects, these are usually manageable and vary in severity. Common side effects include fatigue, itching, and nausea. Serious side effects are less common but can occur. Discuss any concerns with a healthcare provider, who can provide detailed information based on individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for Merkel cell carcinoma?

Pembrolizumab is unique because it empowers the immune system to specifically target and destroy cancer cells in Merkel Cell Carcinoma. Unlike traditional treatments like surgery, radiation, or chemotherapy, pembrolizumab is an immunotherapy that works by blocking the PD-1 pathway, which cancer cells often exploit to hide from the immune system. This approach can lead to longer-lasting responses and potentially fewer side effects, making researchers optimistic about its potential to improve patient outcomes.

What evidence suggests that pembrolizumab might be an effective treatment for Merkel cell carcinoma?

Research has shown that pembrolizumab can help treat Merkel cell carcinoma, a rare and aggressive type of skin cancer. One study found that pembrolizumab helped shrink tumors in more than half of the patients. This drug boosts the immune system to find and attack cancer cells. In this trial, participants will receive pembrolizumab as part of their treatment regimen. Doctors often use pembrolizumab as the first treatment for advanced cases of this cancer. These findings offer hope for people with Merkel cell carcinoma, suggesting pembrolizumab could help manage the disease. ^{3 6 7 8 9}

Who Is on the Research Team?

John Miura, MD

Principal Investigator

Penn Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with resectable stage I-III Merkel Cell Carcinoma (MCC). Participants must have a measurable tumor, provide tissue samples, agree to use contraception if applicable, and not be pregnant or breastfeeding. They should have good performance status and organ function. Those with certain hepatitis conditions may qualify but can't join if they've had recent cancer treatments, live vaccines, active infections including HIV/HBV/HCV, severe allergies to pembrolizumab components or certain medical conditions.

Inclusion Criteria

You have given a sample of your tumor tissue from the past or a new biopsy.

I am not pregnant, not breastfeeding, and follow the contraceptive guidelines.

My tumor is large enough for a biopsy needed before surgery.

Exclusion Criteria

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

You have a strong allergic reaction to pembrolizumab or any of its ingredients.

I have been diagnosed with HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive one dose of pembrolizumab 400mg before surgery

3 weeks

1 visit (in-person)

Surgery

Participants undergo curative intent resection of all remaining disease

1 day

1 visit (in-person)

Adjuvant Treatment

Post-operatively, participants receive pembrolizumab 400mg every 6 weeks for up to 1 year

12 months

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests the effects of pembrolizumab on MCC when given before surgery. It aims to see if this treatment reduces the risk of cancer coming back post-surgery. The drug's side effects will also be monitored in patients who receive it as part of their pre-and post-operative care.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Study participants will undergo a tumor tissue collection biopsy prior to treatment, followed by one dose of pembrolizumab 400mg, then undergo a curative intent resection of all remaining disease 3 weeks after the initial dose of pembrolizumab. Post-operatively, subjects will receive up to 1 year of pembrolizumab 400mg every 6 weeks.

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Merck Sharp & Dohme LLC

Industry 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 (KEYTRUDA) received accelerated FDA approval for treating recurrent locally advanced or metastatic Merkel cell carcinoma (MCC) based on a study of 50 patients, showing an overall response rate of 56% and a complete response rate of 24%.

The treatment demonstrated promising durability, with 96% of responding patients maintaining their response for over 6 months, and 54% for over 12 months, although common side effects included fatigue, pain, and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma. Bradford, D., Demko, S., Jin, S., et al.[2021]

In a phase II trial involving 116 patients with metastatic Merkel cell carcinoma (mMCC), first-line treatment with avelumab resulted in a 39.7% objective response rate and a 30.2% durable response rate, indicating its efficacy in this aggressive skin cancer.

The treatment was generally well-tolerated, with 81% of patients experiencing treatment-related adverse events, but only 18.1% had severe (grade 3/4) events, and there were no treatment-related deaths, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. D'Angelo, SP., Lebbé, C., Mortier, L., 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 88 patients with metastatic Merkel cell carcinoma (mMCC) treated with avelumab, the objective response rate was 33%, with a median duration of response lasting 40.5 months, indicating significant long-term efficacy.

The long-term safety profile of avelumab was favorable, with no new adverse events reported and no treatment-related deaths, supporting its use as a standard treatment for mMCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. D'Angelo, SP., Bhatia, S., Brohl, AS., 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 (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]

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) 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]

In a multicenter phase II trial involving 50 patients with advanced Merkel cell carcinoma (MCC), pembrolizumab treatment resulted in a 58% overall response rate, with 30% achieving complete responses and a median progression-free survival of 16.8 months.

The study found that factors such as better baseline performance status, greater tumor reduction, and completion of 2 years of treatment were linked to improved survival outcomes, with a 3-year overall survival rate of 59.4% for all patients and 89.5% for responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. Nghiem, P., Bhatia, S., Lipson, EJ., et al.[2023]

In the JAVELIN Merkel 200 part B trial, first-line treatment with avelumab showed a high confirmed objective response rate of 62.1% in patients with distant metastatic Merkel cell carcinoma (mMCC), indicating its efficacy as an initial therapy.

Avelumab was generally well tolerated, with no treatment-related deaths or severe adverse events reported, suggesting a favorable safety profile for patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial. D'Angelo, SP., Russell, J., Lebbé, C., et al.[2020]

Avelumab, an anti-PD-L1 treatment, showed a median overall survival (OS) of 12.6 months in patients with metastatic Merkel cell carcinoma (mMCC) who had previously undergone chemotherapy, with a 5-year OS rate of 26%.

Patients with PD-L1 positive tumors had a better median OS of 12.9 months compared to 7.3 months for those with PD-L1 negative tumors, indicating that PD-L1 status may influence treatment outcomes with avelumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in patients with previously treated metastatic Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after >5 years of follow-up. D'Angelo, SP., Bhatia, S., Brohl, AS., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6424137/

Durable Tumor Regression and Overall Survival in Patients ... Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with an associated 5-year overall survival (OS) rate of 14% to 27% for advanced or unresectable ...

2. keytrudahcp.com keytrudahcp.com/efficacy/merkel-cell-carcinoma/

KEYNOTE-017 - Advanced Merkel Cell Carcinoma (MCC) - HCP Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3 ...

3. merkelcell.org merkelcell.org/news-and-publications/2024/pembrolizumab-for-the-first-line-treatment-of-recurrent-locally-advanced-or-metastatic-merkel-cell-carcinoma-results-from-the-single-arm-open-label-phase-iii-keynote-913-study/

Pembrolizumab for the First-Line Treatment of Recurrent ... Immunotherapy is a type of drug that boosts the immune system and can help fight against Merkel cell carcinoma (MCC).

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1603702

PD-1 Blockade with Pembrolizumab in Advanced Merkel ... In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02267603

NCT02267603 | Pembrolizumab in Treating Patients With ... This phase II trial studies how well pembrolizumab works in treating patients with Merkel cell cancer that cannot be removed by surgery or controlled with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39377880/

Pembrolizumab for the First-Line Treatment of Recurrent ... Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924000066

Safety profile of pembrolizumab monotherapy based on an ... This pooled analysis of 31 clinical trials showed that pembrolizumab has a consistent safety profile across indications.

8. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf or metastatic Merkel cell carcinoma (MCC). 1.16 Renal Cell Carcinoma ... Safety data are available for the first 203 patients who received KEYTRUDA and.

9. jitc.bmj.com jitc.bmj.com/content/9/4/e002478

Three-year survival, correlates and salvage therapies in ... Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma.