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

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to determine the response of Merkel cell carcinoma to pembrolizumab before surgery and to determine whether it further reduces the risk for disease recurrence. Another purpose of this study is to look at the side effects that occur when the experimental drug pembrolizumab is given to people with Merkel cell carcinoma before and after their standard of care surgery to remove the Merkel cell carcinoma.

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.

What data supports the effectiveness of the drug pembrolizumab for treating Merkel cell carcinoma?

Pembrolizumab was granted accelerated approval by the FDA for treating Merkel cell carcinoma based on a trial where 56% of patients showed a positive response, with 24% achieving complete tumor disappearance. Additionally, 96% of those who responded maintained their response for over 6 months, and 54% for over 12 months. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been studied for safety in various conditions, including Merkel cell carcinoma and melanoma. Common side effects include fatigue, muscle pain, decreased appetite, itching, diarrhea, nausea, rash, fever, cough, and constipation. Some patients may experience immune-related side effects like thyroid issues or lung inflammation. ^{4 6 7 8 9}

How does the drug pembrolizumab differ from other treatments for Merkel cell carcinoma?

Pembrolizumab is unique because it is an anti-PD-1 therapy that helps the immune system attack cancer cells by blocking a specific protein (PD-1) on T cells, which is different from other treatments like avelumab that target PD-L1. It was granted accelerated approval for treating advanced Merkel cell carcinoma, providing a new option for this aggressive cancer. ^{1 4 6 10 11}

Research Team

John Miura, MD

Principal Investigator

Penn Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 (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 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]

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, 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) 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]

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]

References

1. England 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. [2021]

2. England 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. [2022]

3. England 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

FDA Accelerated Approval of Pembrolizumab for Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

11. United States 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. [2020]