Pembrolizumab for Squamous Cell Carcinoma

Not currently recruiting at 245 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Active infection, Autoimmune disease, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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: 9

Duration: 54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if pembrolizumab, an immunotherapy drug, is more effective than a placebo in preventing the return of squamous cell skin cancer after surgery and radiation. Participants will receive either pembrolizumab or a placebo through an IV to assess which is more effective at preventing cancer recurrence. The trial is suitable for individuals who have undergone surgery for locally advanced squamous cell skin cancer, completed radiation therapy, and are currently cancer-free. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have received certain cancer therapies or live vaccines recently, you may not be eligible to participate.

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

Research has shown that pembrolizumab, also known as Keytruda, is generally well-tolerated in various cancer studies. In one study, pembrolizumab provided lasting benefits over five years, with no new safety issues identified. Another study demonstrated that using pembrolizumab before or after surgery did not introduce any new safety concerns. These findings suggest that pembrolizumab is considered safe based on previous research. However, participants may still experience side effects, which should be discussed with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for squamous cell carcinoma?

Pembrolizumab is unique because it targets the PD-1 pathway, a mechanism that helps the immune system recognize and attack cancer cells more effectively. Unlike traditional chemotherapy, which directly kills rapidly dividing cells, pembrolizumab boosts the body's own immune response, potentially leading to longer-lasting control of squamous cell carcinoma. Researchers are excited about pembrolizumab because it offers a more targeted approach with the potential for fewer side effects and improved outcomes for patients with this type of cancer.

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

Research has shown that pembrolizumab effectively treats squamous cell carcinoma, a type of skin cancer. In a previous study, pembrolizumab provided lasting benefits for patients with advanced or spreading cutaneous squamous cell carcinoma. Patients experienced significant improvements, and no new safety issues emerged over a long period. Additionally, pembrolizumab has proven effective in treating other cancers, such as head and neck squamous cell carcinoma, by slowing the cancer's progression. In this trial, participants will receive either pembrolizumab or a placebo. These findings suggest that pembrolizumab could help prevent cancer recurrence in patients with high-risk advanced cutaneous squamous cell carcinoma. ^{3 4 6 7 8}

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 adults with high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) who've had surgery and radiotherapy. They must be disease-free post-treatment, not pregnant or breastfeeding, and have a life expectancy over 3 months. Excluded are those with active cancer other than LA cSCC, recent live vaccines, certain prior treatments including anti-PD-1/L1/L2 agents within 4 weeks, unresolved radiation toxicities, autoimmune diseases needing treatment in the past 2 years, or organ transplants.

Inclusion Criteria

I had surgery to remove all visible skin cancer, but some tiny cancer cells might remain.

Is not a woman of childbearing potential (WOCBP)

My cancer is a type of skin cancer that started in the skin cells.

Exclusion Criteria

I have received a transplant from another person.

Has a known history of human immunodeficiency virus (HIV) infection

I have a type of skin cancer that is not squamous cell carcinoma and it hasn't been fully treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab or placebo by IV infusion every 42 days for up to 9 cycles

54 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 60 months

Open-label extension (optional)

Participants may receive up to 18 additional cycles of pembrolizumab if they experience biopsy-proven-disease recurrence

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Placebo

Trial Overview The study tests pembrolizumab against a placebo to see if it can prevent cancer from coming back after surgery and radiation in patients with LA cSCC. Participants will randomly receive either pembrolizumab or a placebo without knowing which one they're getting (double-blind). The main goal is to compare how long each group stays cancer-free.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Participants receive 400 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants that complete 9 cycles of pembrolizumab and experience biopsy-proven-disease recurrence may be eligible to receive up to 18 additional cycles of pembrolizumab in an open-label design.

Group II: Placebo Placebo Group 1 Intervention

Participants receive placebo by IV infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants treated with placebo who experience biopsy-proven-disease recurrence may be eligible to receive up to 18 cycles of pembrolizumab in an open-label design.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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 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, 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 phase II trial involving 159 patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma, pembrolizumab showed significant antitumor activity, with an objective response rate of 50.0% in the locally advanced cohort and 35.2% in the recurrent/metastatic cohort.

The treatment demonstrated a manageable safety profile, with only 11.9% of patients experiencing grade 3-5 treatment-related adverse events, indicating that pembrolizumab is a promising and durable treatment option for cSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial. Hughes, BGM., Munoz-Couselo, E., Mortier, L., et al.[2022]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

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 phase III trial involving 1,019 patients with resected high-risk stage III melanoma, pembrolizumab significantly prolonged recurrence-free survival (RFS) compared to placebo, with a 3-year RFS rate of 63.7% versus 44.1%.

The benefits of pembrolizumab were consistent across various patient subgroups, including those with different tumor stages and BRAF mutation statuses, indicating its broad efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial. Eggermont, AMM., Blank, CU., Mandala, M., et al.[2023]

In a study of 39 patients with unresectable cutaneous squamous cell carcinomas (CSCCs), first-line treatment with pembrolizumab showed an objective response rate of 41% at week 15, indicating significant anti-tumor activity, especially in patients with PD-L1 positive tumors (55% response rate).

The treatment was generally well-tolerated, with 71% of patients experiencing adverse events, but only 7% had severe (grade ≥ 3) side effects, suggesting that pembrolizumab has a manageable safety profile while providing durable responses in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas. Maubec, E., Boubaya, M., Petrow, P., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36219809/

Updated Results of the Phase III KEYNOTE-048 Study - PubMed Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9554

Long-term results of the phase 2 KEYNOTE-629 study. With a median follow-up of more than 5 years, pembro continued to show durable responses in pts with LA or R/M cSCC. No new safety signals were observed.

3. keytrudahcp.com keytrudahcp.com/efficacy/hnscc-squamous-cell-carcinoma/

KEYNOTE-689 - Clinical Trial Results | HCP In the neoadjuvant phase of KEYNOTE-689, of the 361 patients who received at least one dose of single agent KEYTRUDA, 11% experienced serious adverse reactions.

4. merck.com merck.com/news/european-commission-approves-keytruda-pembrolizumab-as-part-of-a-treatment-regimen-for-adults-with-resectable-locally-advanced-head-and-neck-squamous-cell-carcinoma-la-hnscc-expressing-pd-l1/

European Commission Approves KEYTRUDA® ... Among the patients with tumors expressing PD-L1 (CPS ≥1), median EFS was doubled to 59.7 months (95% CI, 37.9-not reached) in the KEYTRUDA arm versus 29.6 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694497/

Real-World Evidence on the Effectiveness of Pembrolizumab ... Monotherapy improved the overall response rate compared to combination therapy. No significant difference in progression-free survival and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7460151/

Pembrolizumab Monotherapy for Recurrent or Metastatic ... Patients experienced rapid tumor reduction after 6 weeks of pembrolizumab treatment (Fig 2 and Data Supplement). FIG 2. FIG 2. Open in a new tab. Effects of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03284424

NCT03284424 | Study of Pembrolizumab (MK-3475) in ... The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in adult participants with recurrent or metastatic(R/M) ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... Neoadjuvant pembrolizumab did not affect the likelihood of surgical completion. No new safety signals were identified. (Funded by Merck Sharp ...