Imiquimod + Pembrolizumab for Skin Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mayo Clinic

Must not be taking: Anti-PD1, Anti-PDL1

Disqualifiers: HIV, Active TB, Hepatitis B/C, others

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

Compensation: Varies

Number of Visits: 18

Duration: Up to 2 years

7 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies the effects of combining imiquimod and pembrolizumab to treat advanced melanoma. Imiquimod boosts the immune system, and pembrolizumab helps the immune system attack cancer cells. Pembrolizumab is a standard treatment for advanced melanoma, and imiquimod has shown promise in treating melanoma metastases. The goal is to see if this combination works better than current treatments.

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, it mentions that you should not have received certain cancer treatments recently, and you should not have active infections or uncontrolled illnesses. It's best to discuss your current medications with the trial team to be sure.

Is the combination of Imiquimod and Pembrolizumab safe for treating skin cancer?

Pembrolizumab, also known as KEYTRUDA, has been shown to be generally safe in humans, with common side effects including fatigue, rash, itching, and diarrhea. Less common side effects can include inflammation of the lungs (pneumonitis), thyroid issues, and liver inflammation (hepatitis). ^{1 2 3 4 5}

How is the drug combination of Imiquimod and Pembrolizumab unique for treating skin cancer?

This treatment is unique because it combines Imiquimod, a topical cream that boosts the immune response to fight skin cancer, with Pembrolizumab, an injectable drug that helps the immune system attack cancer cells by blocking a pathway that tumors use to hide from immune cells. This combination leverages both local and systemic immune activation, offering a novel approach compared to traditional treatments like surgery or single-drug therapies. ^{1 6 7 8 9}

What data supports the effectiveness of the drug Pembrolizumab for skin cancer?

Pembrolizumab has shown strong antitumor activity in skin cancer, specifically in recurrent/metastatic cutaneous squamous cell carcinoma, with meaningful and lasting effects. It has also been effective in treating melanoma, another type of skin cancer, with high response rates and low toxicity. ^{1 6 10 11 12}

Who Is on the Research Team?

Ruqin Chen, MD, MB

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with stage IIIB-IV melanoma who haven't had pembrolizumab or similar therapies for metastatic disease. They must have a treatable skin lesion, confirmed diagnosis not suitable for surgery, good performance status and lab values, no severe diseases that could interfere with the trial, no active infections or certain heart conditions, and be willing to use contraception.

Inclusion Criteria

Women who can have children must have a negative pregnancy test.

Willing to return to enrolling institution for follow-up

I have not been treated with pembrolizumab or similar drugs for my metastatic disease.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I haven't used any experimental treatments or devices for my cancer in the last 4 weeks.

Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5, with cycles repeating every 21 days for up to 2 years

Up to 2 years

Biopsy at baseline, 6 weeks, and 12 weeks; imaging throughout

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 3 years

Every 12 weeks for 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Imiquimod
• Pembrolizumab

Trial Overview The study tests how well imiquimod (which stimulates the immune system) combined with pembrolizumab (an antibody that may stop tumor growth) treats advanced melanoma. It's a pilot trial to see if this combination works better than current treatments.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, imiquimod) Experimental Treatment 6 Interventions

Patients receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Cycles repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline, 6 weeks, and 12 weeks and CT, PET/CT, or MRI throughout the trial.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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 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 randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

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 (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 (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]

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]

Imiquimod is an effective TLR7 agonist that modifies the immune response and is currently used to treat actinic keratoses and superficial basal cell carcinoma.

The treatment regimen for superficial basal cell carcinoma involves a 6-week application of imiquimod, providing a non-surgical alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical treatment of basal cell carcinoma with the immune response modifier imiquimod. Papakostas, D., Stockfleth, E.[2018]

The study developed nanostructured lipid carriers (NLCs) for imiquimod (IMQ), which significantly improved the drug's deposition in deeper skin layers compared to the commercial cream, enhancing its potential efficacy for treating skin conditions.

The optimized IMQ-NLC formulation was incorporated into a matrix-type patch, which not only improved drug delivery but also aimed to be more patient-friendly and environmentally sustainable, addressing common issues with topical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach. Kim, S., Abdella, S., Abid, F., et al.[2023]

Citations

1. England pubmed.ncbi.nlm.nih.gov

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

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

4. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab superior to ipilimumab in melanoma. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]

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

Topical treatment of basal cell carcinoma with the immune response modifier imiquimod. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Digital follow-up by means of dermatoscopy and reflectance confocal microscopy of actinic keratosis treated with Imiquimod 3.75% cream. [2021]

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

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach. [2023]