Avelumab +/− Cetuximab for Skin Cancer

Recruiting at 448 trial locations

Overseen By Dan P. Zandberg, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Immunosuppressants, Anti-PD-1, Anti-PD-L1

Disqualifiers: Active infection, Autoimmune disease, others

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

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: 4

Duration: 24 months

60 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medication within 7 days of registration, except for certain types like inhaled or topical steroids, or low-dose systemic corticosteroids.

What data supports the effectiveness of the drug Avelumab in treating skin cancer?

Avelumab has shown effectiveness in treating metastatic Merkel cell carcinoma (a type of skin cancer) and has been approved by the FDA for this use. It works by blocking a protein that helps cancer cells hide from the immune system, allowing the body to better fight the cancer. ^{1 2 3 4 5}

What safety data exists for Avelumab and Cetuximab in humans?

Avelumab has been shown to be generally safe in humans, with common side effects including infusion-related reactions and fever, as observed in patients with Merkel cell carcinoma. Cetuximab, used for colorectal cancer, often causes skin-related side effects, such as rashes, which vary in severity. ^{1 2 6 7 8}

How is the drug Avelumab unique for treating skin cancer?

Avelumab is unique because it is a monoclonal antibody that targets PD-L1, a protein that helps cancer cells evade the immune system, making it different from traditional chemotherapy. It is administered intravenously and has been approved for treating advanced Merkel cell carcinoma, a rare type of skin cancer, highlighting its novel approach in targeting the immune system. ^{2 3 9 10 11}

What is the purpose of this trial?

This phase II trial studies how well avelumab with or without cetuximab work in treating patients with skin squamous cell cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as avelumab and cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Research Team

Dan P. Zandberg, MD

Principal Investigator

University of Pittsburgh Medical Center Hillman Cancer Center

Eligibility Criteria

This trial is for adults with advanced skin squamous cell cancer that's spread or can't be removed by surgery. Participants need enough tissue for PD-L1 testing, measurable disease, normal organ function tests, and no recent major surgeries. They must not have had certain past treatments like cetuximab (unless it was over 6 months ago) or anti-PD-1/L1 drugs, autoimmune diseases needing immunosuppression, serious infections or heart issues.

Inclusion Criteria

I have fully recovered from any major surgery before starting treatment.

Platelet count >= 100,000/mm^3

My skin cancer cannot be removed with surgery or has spread.

Exclusion Criteria

I have not received a live vaccine in the last 4 weeks.

I have never had a severe reaction to cetuximab that stopped my treatment.

I have never had serious heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive avelumab and/or cetuximab intravenously in cycles, with treatment repeating every 28 days

24 months

Visits on days 1, 8, 15, and 22 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

Every 3 months until disease progression, then every 6 months

Treatment Details

Interventions

• Avelumab
• Cetuximab

Trial Overview The study is examining the effectiveness of avelumab alone versus combined with cetuximab in treating advanced skin squamous cell cancer. Avelumab and cetuximab are both monoclonal antibodies which may boost the immune system to fight cancer cells and prevent their growth.

Participant Groups

Group I: Arm II (Avelumab, cetuximab) Experimental Treatment 2 Interventions

Patients receive cetuximab IV over 1-2 hours on days 1, 8,15, and 22 and avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles for cetuximab and 24 cycles for avelumab in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (Avelumab) Active Control 1 Intervention

Patients receive avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with avelumab failure will crossover to Arm II.

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

Avelumab is an antibody that blocks programmed cell death ligand-1 (PD-L1) and has received accelerated approval in the USA for treating metastatic Merkel cell carcinoma (mMCC) in both adults and children aged 12 and older.

The drug is also undergoing regulatory reviews for other cancer treatments, including urothelial carcinoma, indicating its potential as a versatile cancer therapy in various stages of development worldwide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab: First Global Approval. Kim, ES.[2022]

Avelumab, a PD-L1 inhibitor, has shown overall response rates for advanced Merkel cell carcinoma (MCC) ranging from 29.1% to 72.1% in real-world studies, with median progression-free survival between 8.1 to 24.1 months, indicating its efficacy across diverse populations.

The treatment is generally safe, with common side effects including fatigue and infusion-related reactions, and it appears to be particularly effective in immunosuppressed patients, although further research is needed to evaluate long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival. Lohray, R., Verma, KK., Wang, LL., et al.[2023]

In a phase 2a trial involving 43 patients with advanced squamous non-small cell lung cancer (NSCLC), the combination of avelumab and cetuximab with chemotherapy resulted in a 34.9% objective response rate, indicating notable antitumor activity.

While the treatment showed tolerable safety, with 88.4% of patients experiencing treatment-related adverse events, the overall response rate was not significantly better than existing standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC. Andric, Z., Gálffy, G., Cobo Dols, M., et al.[2023]

In a review of clinical trials for colorectal cancer, 76.9% of studies on cetuximab reported dermatologic adverse drug reactions (dADRs), with 50% showing a positive correlation between these reactions and patient survival, indicating that dADRs may be relevant for treatment outcomes.

In contrast, only 42.9% of studies on panitumumab reported dADRs, highlighting significant variability in reporting practices, which limits the ability to assess patient risk and compare the safety profiles of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Completeness in the reporting of dermatologic adverse drug reactions associated with monoclonal antibody epidermal growth factor receptor inhibitors in phase II and III colorectal cancer clinical trials. Bauer, KA., Hammerman, S., Rapoport, B., et al.[2018]

Avelumab, a monoclonal antibody targeting PD-L1, demonstrated an acceptable safety profile in a phase 1a trial with 53 patients, with only one dose-limiting toxicity observed at the highest dose of 20 mg/kg, indicating that the maximum tolerated dose was not reached.

The pharmacokinetic analysis showed a dose-proportional exposure and a half-life of approximately 4 days at higher doses, leading to the selection of 10 mg/kg every 2 weeks for further development, as it achieved over 90% target occupancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Heery, CR., O'Sullivan-Coyne, G., Madan, RA., et al.[2022]

References

1. 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]

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

Avelumab: First Global Approval. [2022]

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

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival. [2023]

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

Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program. [2023]

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

Avelumab expanded access program in metastatic Merkel cell carcinoma: Efficacy and safety findings from patients in Europe and the Middle East. [2022]

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

Completeness in the reporting of dermatologic adverse drug reactions associated with monoclonal antibody epidermal growth factor receptor inhibitors in phase II and III colorectal cancer clinical trials. [2018]

8. Greece pubmed.ncbi.nlm.nih.gov

Long-term Survival with Ipilimumab: Experience from a National Expanded Access Program for Patients with Melanoma. [2022]

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

Diffuse lichen planus-like keratoses and clinical pseudo-progression associated with avelumab treatment for Merkel cell carcinoma, a case report. [2020]

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

Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. [2022]

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

Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study. [2021]