Pembrolizumab for Basal Cell Carcinoma

Overseen By Brian Gastman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Brian Gastman

Must not be taking: Immunosuppressants, Steroids, Live vaccines, others

Disqualifiers: Pregnancy, Active infection, Autoimmune disease, 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)

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: 18

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab (also known as KEYTRUDA or MK-3475), an experimental drug, to determine if it can treat basal cell carcinoma (a type of skin cancer) before surgery and potentially eliminate the need for surgery. Pembrolizumab boosts the immune system's ability to fight cancer by blocking a protein that slows immune responses. This trial targets individuals with advanced basal cell carcinoma, particularly those with tumors larger than 20mm or requiring post-surgery radiation. Participants must have a confirmed diagnosis of basal cell carcinoma and should not have recently undergone certain cancer treatments or immunosuppressive therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

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 must not be on active immunosuppression or have received certain cancer therapies recently. It's best to discuss your specific medications with the study team.

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

Research has shown that pembrolizumab is generally safe for patients with basal cell carcinoma. Past studies with this drug reported no life-threatening side effects or deaths, indicating a good safety record. Pembrolizumab already has FDA approval for treating other cancers, such as certain lung cancers and lymphoma. This approval suggests safety, although its use for basal cell carcinoma remains experimental. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it targets the immune system to fight basal cell carcinoma (BCC) by blocking the PD-1 pathway, which can allow cancer cells to evade immune detection. Unlike traditional treatments for BCC, such as surgical resection or topical therapies, pembrolizumab offers a systemic approach that could potentially treat advanced or inoperable cases. Researchers are excited about pembrolizumab because it harnesses the body’s own immune defense, providing a promising alternative for patients who may not respond well to existing treatments.

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

Research shows that pembrolizumab, the treatment under study in this trial, might help the immune system combat basal cell carcinoma, a type of skin cancer. It blocks a protein called PD-1, which typically slows the immune system. By blocking PD-1, pembrolizumab activates the immune system against cancer cells. In other cancers, such as certain lung and cervical cancers, pembrolizumab has proven beneficial. Although long-term data for basal cell carcinoma remains limited, early signs suggest that pembrolizumab could help control the disease. Previous studies on similar skin cancers also indicate it might be effective. ^{1 2 6 7 8}

Who Is on the Research Team?

James Isaacs, MD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced basal cell carcinoma of the head and neck, large enough to require surgery and possibly post-operative radiation. Participants must not be pregnant or planning pregnancy, have confirmed diagnosis, adequate organ function without severe immunosuppression, no recent cancer other than certain skin cancers or low-grade tumors, and no history of life-threatening virus infections.

Inclusion Criteria

I am fully active or can carry out light work.

I am not pregnant and follow the required birth control measures.

My skin cancer is confirmed as basal cell carcinoma.

Exclusion Criteria

I have received an organ or tissue transplant from another person.

I have a history of HIV or Hepatitis B/C.

I have an immune system disorder or I'm on long-term steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive at least 4 doses of pembrolizumab every 3 weeks before surgery

12 weeks

4 visits (in-person)

Surgery

Participants undergo standard surgical resection after neoadjuvant treatment

1 week

1 visit (in-person)

Adjuvant Treatment

Participants continue pembrolizumab treatment for approximately 1 year post-surgery

1 year

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests Pembrolizumab as a neoadjuvant (before surgery) therapy in patients with basal cell carcinoma. It aims to see if this treatment can improve outcomes before surgery and potentially eliminate the need for surgery altogether. Pembrolizumab is an experimental drug designed to boost the immune system's response against cancer cells by blocking PD-1 protein receptors.

How Is the Trial Designed?

Group I: Permbrolizumab Experimental Treatment 2 Interventions

Participants will undergo fine cut CT imaging (head and neck) followed by at least 4 doses of pembrolizumab q 3 weeks. After the 4th dose of pembrolizumab as appropriate, patients will undergo standard surgical resection, with all non-marginal tissue as well as the pre-op biopsy to be stored for collateral research. 2 weeks after initial flap or graft insert (which would be equivalent to stage 1 of a forehead flap) patients would continue for a total of approximately 1 year of pembrolizumab q 3 weeks (another 13 doses, thus 17 doses total).

Who Is Running the Clinical Trial?

Brian Gastman

Lead Sponsor

Trials

1

Recruited

10+

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

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, 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 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]

Cemiplimab demonstrated clinically meaningful antitumor activity in patients with locally advanced basal cell carcinoma who had progressed on hedgehog inhibitor therapy, with an objective response rate of 31% in a study of 84 patients.

The treatment had an acceptable safety profile, with 48% of patients experiencing grade 3-4 adverse events, but no treatment-related deaths were reported, indicating it is a viable option for patients intolerant to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Stratigos, AJ., Sekulic, A., Peris, K., 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]

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 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) 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6839543/

Pembrolizumab for advanced basal cell carcinoma There was no significant correlation between prepembrolizumab PD-L1 expression and best percentage change in BCC diameter. There were no life-threatening ...

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

Real-World Evidence on the Effectiveness of Pembrolizumab ... The study showed some beneficial effects of pembrolizumab monotherapy in recurrent/metastatic/unresectable HNSCC patients in real-world scenarios.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02358031

NCT02358031 | A Study of Pembrolizumab (MK-3475) for ... A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

4. sciencedirect.com sciencedirect.com/science/article/pii/S277261182400257X

Long-term control with immunotherapy and aggressive re ... Given scarce long-term data for pembrolizumab use with stage 4 basal cell carcinoma, the current paradigm by the treating team is to continue pembrolizumab ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.TPS9593

Pembrolizumab with or without vismodegib in treating ... Pembrolizumab with or without vismodegib in treating metastatic or unresectable basal cell skin cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11718879/

Therapeutic Approaches for Advanced Basal Cell Carcinoma Pembrolizumab monotherapy yielded an ORR of 44%, compared to 29% in patients receiving combination therapy, resulting in an overall ORR of 38% ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03553836

NCT03553836 | Safety and Efficacy of Pembrolizumab ... This 2-part study will evaluate the safety and efficacy of pembrolizumab (MK-3475) compared to placebo in participants with surgically resected high-risk ...

8. jaad.org jaad.org/article/S0190-9622(18)32471-X/pdf

Pembrolizumab for advanced basal cell carcinoma The primary outcome was the overall response rate (ORR) for all evaluable subjects at. 18 weeks. Sixteen participants, 9 receiving pembrolizumab monotherapy and ...