Pembrolizumab for Skin Cancer

Not currently recruiting at 658 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunotherapy

Disqualifiers: Metastatic disease, Active immunosuppression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: Approximately 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug pembrolizumab works for patients with Merkel cell skin cancer that has been completely removed by surgery. Pembrolizumab, an immunotherapy, may help the immune system fight cancer cells and prevent them from growing or spreading. Participants will be divided into two groups: one receiving pembrolizumab and possibly radiation therapy, and the other receiving standard observation and possibly radiation therapy. The trial seeks individuals who have had their Merkel cell carcinoma surgically removed within the last 16 weeks and are currently free of distant metastatic disease (cancer that has not spread to distant parts of the body). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients must not be on active immunosuppression, which might imply some restrictions on certain medications. 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, also known as Keytruda, has been safely used for other conditions. The FDA has already approved it for treating advanced melanoma, a type of skin cancer. Past studies have demonstrated that pembrolizumab is generally safe, though it can have side effects like many treatments.

Common side effects include loss of appetite, fatigue, shortness of breath, and nausea, occurring in 20% or more of patients in previous studies. The severity of these side effects can vary.

Overall, many patients tolerate pembrolizumab well, but discussing any concerns with a doctor is advisable. They can provide guidance based on individual health and history. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it leverages the power of immunotherapy, specifically targeting the PD-1 pathway to help the body's immune system recognize and attack cancer cells. Unlike traditional treatments for skin cancer, such as chemotherapy or targeted therapies, pembrolizumab offers a novel mechanism that can potentially lead to durable responses and long-term remission. Researchers are excited about pembrolizumab because it has shown promise in enhancing the body's natural defenses with fewer side effects compared to conventional therapies, providing a new hope 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 several types of skin cancer. In studies on advanced melanoma, pembrolizumab helped more than a third of patients live for ten years, outperforming other treatments. It also reduced the risk of cancer spreading or worsening by 42% compared to ipilimumab. Pembrolizumab aids the immune system in attacking cancer cells, preventing their growth. In this trial, participants in Arm A will receive pembrolizumab with radiation therapy. This treatment has also shown promising results in other rare skin cancers, with most patients experiencing positive outcomes. ^{1 3 5 6 7}

Who Is on the Research Team?

Janice Mehnert

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with stage I-IIIb Merkel cell carcinoma, surgically removed within the past 16 weeks. Must have stable blood counts and organ function, no HIV or hepatitis unless under control. Not for those with distant metastases, history of other cancers in last two years (except certain skin cancers), or recent immunotherapy.

Inclusion Criteria

I have hepatitis B or C, but my viral load is undetectable or I am on suppressive therapy.

Creatinine =< 2.0 x institutional upper limit of normal (ULN) (within 4 weeks prior to randomization).

I have Merkel cell carcinoma and haven't had systemic or radiation therapy before surgery, or I finished adjuvant radiation less than 6 weeks ago.

Exclusion Criteria

I am not on immunosuppressants, haven't had severe viruses, other recent cancers except for non-melanoma skin or low-grade prostate cancer, or immunotherapy in the last 2 years.

I will use or am using effective birth control or abstaining from sex while on Pembrolizumab.

Patient must not be pregnant or breast-feeding due to the unknown effects of the study drug in this setting. All patients of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy. A patient of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV every 21 days for up to 17 cycles or undergo standard of care observation

Approximately 12 months

Every 21 days for pembrolizumab arm; every 3 months for observation arm

Radiation

Participants may undergo standard of care radiation therapy within 14 days of day 1, cycle 1

Concurrent with initial treatment phase

Follow-up

Participants are monitored for recurrence free survival and overall survival

Up to 5 years

Every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The trial is testing if pembrolizumab (an immune system booster) is better than just watching patients after surgery for Merkel cell cancer. Patients are randomly chosen to get either pembrolizumab or standard observation post-surgery.

How Is the Trial Designed?

Group I: Arm A (pembrolizumab, radiation therapy) Experimental Treatment 6 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1. Patients undergo PET-CT, CT, or MRI throughout the trial. Patients may also undergo blood and urine sample collection as clinically indicated at the discretion of the treating investigator.

Group II: Arm B (standard of care observation, radiation therapy) Active Control 6 Interventions

Patients receive standard of care observation every 3 months for 1 year, and then every 6 months for 5 years. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1. Patients undergo PET-CT, CT, or MRI throughout the trial. Patients may also undergo blood and urine sample collection as clinically indicated at the discretion of the treating investigator.

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

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 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]

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) 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) 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, 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 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]

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

Specifically, in the KEYNOTE-001 study on advanced melanoma, pembrolizumab monotherapy resulted in a 3-year overall survival (OS) of 41% in patients previously ...

3.

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 ...

4.

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 ...

5.

aacr.org

aacr.org/about-the-aacr/newsroom/news-releases/single-agent-pembrolizumab-may-benefit-patients-with-rare-type-of-skin-cancer/

Single-agent Pembrolizumab May Benefit Patients with ...

Monotherapy with pembrolizumab (Keytruda) led to clinical responses in 89% of patients with unresectable metastatic desmoplastic melanoma.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12454464/

Real-World Outcomes of Pembrolizumab in Advanced ...

Most available real-world safety data on ICIs in melanoma are derived from US-based studies [47–51], where differences in clinical practice ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ...

The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.