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

13 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate anti-PD-1 Neoadjuvant therapy in Basal cell carcinoma to provide a better outcome when administered prior to surgery and provide a therapeutic strategy to avoid surgery altogether. The study team will gather information about how Basal cell carcinoma responds to Pembrolizumab prior to surgery and to gather information about recurrence rates. Pembrolizumab, is an investigational (experimental) drug that may improve the response of the immune system against cancer. Pembrolizumab is a manufactured antibody, much like the antibodies usually made by the human body to fight off infection. The idea behind developing this experimental drug is to stimulate the body's immune system to kill cancer cells. Pembrolizumab antibody has been specifically made to block a program cell death-1 (PD-1) protein receptor, which is found on cells of the immune system. PD-1 receptor seems to slow down the immune response. Blocking PD-1 with pembrolizumab antibody may make the immune response more active and may improve the response of the immune system against cancer. Pembrolizumab is currently FDA approved for use in other malignancies. It has been used to treat a number of other diseases such as certain types of lung cancer, cervical cancer and lymphoma. The use of Pembrolizumab in this study is experimental because it is not approved by the Food and Drug Administration (FDA) for use in the treatment of Basal cell carcinoma.

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.

What data supports the effectiveness of the drug pembrolizumab for treating basal cell carcinoma?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, was effective in a patient with basal cell carcinoma who had not responded to other treatments. Additionally, pembrolizumab has shown success in treating other skin cancers, suggesting it could be beneficial for basal cell carcinoma as well. ^{1 2 3 4 5}

Is pembrolizumab generally safe for humans?

Pembrolizumab has been studied in various conditions, and common side effects include fatigue, cough, nausea, and rash. Some rare but serious immune-related side effects can affect organs like the thyroid and pancreas, leading to conditions such as type 1 diabetes. ^{2 6 7 8 9}

How does the drug pembrolizumab differ from other treatments for basal cell carcinoma?

Pembrolizumab is unique because it is an immunotherapy drug that works by blocking the PD-1 receptor on T cells, which helps the immune system attack cancer cells. This mechanism is different from traditional treatments like surgery or drugs targeting specific cancer pathways, making it a novel option for patients who do not respond to other therapies. ^{1 8 10 11 12}

Research Team

James Isaacs, MD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 (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]

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 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 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) 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]

References

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

Effective anti-programmed death-1 therapy in a SUFU-mutated patient with Gorlin-Goltz syndrome. [2019]

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

Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade. [2023]

4. Australia pubmed.ncbi.nlm.nih.gov

Combination treatment of bilateral periocular sebaceous carcinomas with microsatellite instability with neoadjuvant pembrolizumab and Mohs surgery. [2023]

5. England 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. [2021]

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

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

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

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

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

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

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

Pembrolizumab: first global approval. [2021]

12. England pubmed.ncbi.nlm.nih.gov

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