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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining imiquimod and pembrolizumab for individuals with advanced melanoma, a type of skin cancer. Imiquimod is believed to boost the immune system, while pembrolizumab, a monoclonal antibody, may help the body attack cancer cells and prevent their spread. The trial seeks patients with stage IIIB-IV melanoma who have not previously received pembrolizumab or similar therapies and have at least one treatable skin lesion. Participants will follow a set treatment schedule and attend regular check-ups to monitor the cancer's response. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel combination therapy.

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

Research has shown that both imiquimod and pembrolizumab are being tested for their safety in treating skin cancer. Imiquimod is a cream that helps the immune system fight cancer cells, while pembrolizumab boosts the body's natural defenses to attack cancer.

In past studies, patients who received only pembrolizumab showed promising results. Specifically, one study found that 44% of patients experienced tumor shrinkage. However, like many treatments, side effects such as tiredness and skin reactions can occur and vary among individuals.

This trial is in an early stage, so researchers are still assessing the safety and tolerability of these treatments when used together. As the trial is just beginning, detailed safety information for the combination is not yet available. The aim is to understand how these treatments work together and their potential benefits for people with advanced melanoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of imiquimod and pembrolizumab for skin cancer because it brings together two powerful mechanisms. Imiquimod is a topical cream that boosts the local immune response directly on the skin, while pembrolizumab is an immune checkpoint inhibitor delivered via IV that helps the body's immune system recognize and attack cancer cells throughout the body. This dual approach could potentially enhance the overall effectiveness of treatment by targeting skin cancer both locally and systemically, unlike the standard treatments that typically focus on one method at a time.

What evidence suggests that imiquimod and pembrolizumab might be effective for melanoma?

Research shows that pembrolizumab, a treatment that aids the immune system, effectively fights cancer cells, particularly in advanced melanoma. Studies have found that pembrolizumab can slow tumor growth and sometimes shrink tumors. Imiquimod, a cream, also helps the immune system combat cancer. In this trial, participants will receive both imiquimod and pembrolizumab, as researchers are investigating whether this combination might more effectively attack melanoma. Early results suggest this combination could be promising for treating advanced skin cancer by enhancing the body's immune response. ^{1 3 6 7 8}

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

Willing to return to enrolling institution for follow-up

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

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

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]

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]

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]

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]

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]

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, 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03276832

NCT03276832 | Imiquimod and Pembrolizumab in Treating ... This pilot early phase I trial studies the side effects and how well imiquimod and pembrolizumab work in treating patients with stage IIIB-IV melanoma.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9947410/

Classic and new strategies for the treatment of advanced ... Studies on immunotherapy and target therapies in melanoma and NMSCs are rapidly increasing. BRAF and MEK inhibitors improve clinical outcomes.

3. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/skin-cancer

Skin Cancer Clinical Trials This pilot trial studies the side effects and how well imiquimod and pembrolizumab work in treating patients with stage IIIB-IV melanoma. Imiquimod may ...

4. stanfordhealthcare.org stanfordhealthcare.org/trials/t/NCT03063632.html

Testing the Combination of Two Experimental Drugs MK ... This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and Sezary syndrome.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5028964/

Current clinical trials testing the combination of ... Studies have shown that PD-1 and PD-L1 targeted therapies have clinical activity against metastatic bladder cancer, head and neck cancers, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10559482/

Skin cancer: understanding the journey of transformation from ... Nivolumab and ipilimumab in combination showed persistent, improved clinical outcomes than monotherapy in trial participants with advanced melanoma. 7, 5-FU ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8720968/

Immune Checkpoint Inhibition in Non-Melanoma Skin Cancer Of the 9 patients who received pembrolizumab alone, 44% (n=4) achieved partial responses with a median (DOR) of 67.6 weeks. Among the 7 patients ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03063632

Study Details | NCT03063632 | Testing the Combination of ... This phase II trial studies how well pembrolizumab and interferon gamma-1b work in treating patients with stage IB-IVB mycosis fungoides and Sezary syndrome.