Immunotherapy for Skin Cancer

Overseen By Rachel Piecuch, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Diwakar Davar

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Autoimmune disease, Active infection, others

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

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: 19

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, a type of immunotherapy, to determine its effectiveness against high-risk skin cancer before surgery. The focus is on cutaneous squamous cell carcinoma (cSCC), a type of skin cancer not yet treated surgically. The goal is to see if this treatment can improve the chances of remaining cancer-free. Individuals with high-risk cSCC who have not undergone surgery might be suitable candidates. As a Phase 2 trial, the research measures 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, you cannot participate if you are on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the trial starts. It's best to discuss your specific medications with the trial team.

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

Research has shown that pembrolizumab is generally safe across different conditions. A review of 31 clinical trials found that most patients tolerated the treatment well. Some side effects, such as tiredness and skin rash, were noted but were usually manageable. The FDA has already approved pembrolizumab for treating other skin cancers, such as melanoma, indicating its relative safety. However, discussing the possible risks and benefits with a doctor before joining a clinical trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it leverages the body's immune system to fight skin cancer. Unlike traditional chemotherapy, which directly targets and kills cancer cells, pembrolizumab is an immunotherapy. It works by blocking a protein called PD-1, allowing immune cells to better recognize and attack cancer cells. Researchers are excited about pembrolizumab because it offers a targeted approach with the potential for fewer side effects and improved outcomes for patients with skin cancer.

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

Research has shown that pembrolizumab, also known as KEYTRUDA, effectively treats certain types of cancer. Studies on advanced melanoma, a type of skin cancer, have found that pembrolizumab can significantly reduce the risk of the cancer spreading or worsening. In some cases, it helped patients live longer, with more than one-third surviving beyond ten years. This trial will administer pembrolizumab to participants to evaluate its effectiveness specifically for cutaneous squamous cell carcinoma (cSCC). The success in treating melanoma suggests potential benefits for other skin cancers. Overall, pembrolizumab has a history of improving outcomes in high-risk cancer cases. ^{5 6 7 8 9}

Who Is on the Research Team?

Diwaker Davar, MD, M.Sc

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

Adults with high-risk cutaneous squamous cell carcinoma (cSCC) that hasn't been surgically removed may join this trial. They must have measurable disease, be in good health otherwise, and women of childbearing age must agree to contraception. People can't join if they've had recent cancer treatments, immune system issues, certain other cancers within 3 years, or are pregnant.

Inclusion Criteria

My organs are functioning well.

The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

I agree to use contraception and not donate sperm for 120 days after my last treatment dose.

Exclusion Criteria

Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 120 days after the last dose of trial treatment

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

You have mental health or drug problems that might make it difficult for you to follow the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Neoadjuvant Phase

Participants receive pembrolizumab peri-operatively for 6 weeks prior to definitive surgery

6 weeks

2 visits (in-person, every 3 weeks)

Surgical Phase

Participants undergo restaging scans and surgical evaluation followed by definitive surgical resection

1 week

1 visit (in-person)

Adjuvant Phase

Post-operatively, participants receive 15 cycles of pembrolizumab over a 45-week period, with concurrent RT if eligible

45 weeks

15 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The study is testing Pembrolizumab injections as a pre-surgery treatment for cSCC over a year. It aims to see if the drug helps prevent cancer from coming back after surgery in patients who haven't received PD-1 inhibitors before.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Neoadjuvant Phase: 200 mg IV infusion, every 3 weeks (Day 1 of each 3-week cycle, 2 cycles) Adjuvant Phase: Day 1 of each 3-week cycle, 15 cycles

Who Is Running the Clinical Trial?

Diwakar Davar

Lead Sponsor

Trials

12

Recruited

420+

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

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, 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 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 used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

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]

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, 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 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 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 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]

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]

Citations

1.

merck.com

merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ...

At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

2.

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

In advanced melanoma, KEYTRUDA reduced the risk of cancer spreading, growing, or getting worse by 42% compared to ipilimumab. Half of the people who received ...

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(19)31110-X/fulltext

Five-year survival outcomes for patients with advanced ...

KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients ...

5.

keytrudahcp.com

keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab)

The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%). In KEYNOTE⁠-⁠054, when KEYTRUDA was ...

6.

mayoclinic.org

mayoclinic.org/drugs-supplements/pembrolizumab-intravenous-route/description/drg-20122552

Pembrolizumab (intravenous route) - Side effects & uses

Description. Pembrolizumab injection is used to treat melanoma (a type of skin cancer) that has spread or cannot be removed by surgery.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4665064/

Keytruda (Pembrolizumab): First PD-1 Inhibitor Approved for ...

Pembrolizumab, the first FDA-approved PD-1 inhibitor, is a safe and effective immunotherapy for patients with unresectable or metastatic melanoma and disease ...

8.

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.

9.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/keytruda

Keytruda | European Medicines Agency (EMA)

What benefits of Keytruda have been shown in studies? · Melanoma (skin cancer). Keytruda can delay worsening of melanoma and improve survival. · Non-small cell ...