Avelumab +/− Cetuximab for Skin Cancer

Not currently recruiting at 454 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether avelumab, with or without cetuximab, effectively treats advanced skin squamous cell cancer that has spread. Avelumab and cetuximab are immunotherapies that help the immune system fight cancer and may inhibit cancer cell growth. The trial includes two groups: one receives only avelumab, while the other receives both avelumab and cetuximab. It seeks participants with advanced skin squamous cell cancer that cannot be surgically removed. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that avelumab is generally safe. Patients with advanced skin cancers have received it, and studies indicate that most tolerate it well. Common side effects include tiredness and nausea, but these are usually mild.

Testing has also been done on the combination of avelumab and cetuximab, showing promising results without unexpected safety issues. This combination has been studied in people with hard-to-treat skin cancers and has improved outcomes while maintaining a similar safety level.

In summary, previous studies have shown that both treatments—avelumab alone and avelumab with cetuximab—are safe. Most side effects are mild and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Avelumab and Cetuximab offer a new approach to fighting skin cancer. Avelumab is a type of immunotherapy called a PD-L1 inhibitor, which works by helping the immune system recognize and attack cancer cells. Cetuximab, on the other hand, is an antibody that targets the epidermal growth factor receptor (EGFR), which is involved in the growth and spread of cancer cells. The combination of these two drugs could potentially enhance the effectiveness of treatment by attacking the cancer from different angles compared to standard therapies like chemotherapy and radiation. This dual approach could lead to better outcomes for patients with skin cancer.

What evidence suggests that this trial's treatments could be effective for skin cancer?

Research shows that avelumab, which participants in this trial may receive, holds promise for treating certain types of cancer. Studies have shown that 73% of patients responded to avelumab, experiencing longer periods without cancer progression. In this trial, some participants will receive avelumab alone, while others will receive a combination of avelumab and cetuximab. Research has found that this combination can improve outcomes for patients with advanced skin cancer. The combination appears more effective than avelumab alone, possibly because the two drugs complement each other. This suggests that both avelumab alone and in combination with cetuximab could effectively treat metastatic skin squamous cell cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Dan P. Zandberg, MD

Principal Investigator

University of Pittsburgh Medical Center Hillman Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9394192/

Real-world clinical outcomes with avelumab in patients with ... Patients with avelumab treatment had an rwORR of 73% (95% CI: 64 to 83), median rwPFS of 24.4 months (95% CI: 8.31 to not estimable (NE)), and median OS of 30.7 ...

2. bavencio.com bavencio.com/en_US/patients-and-caregivers/mcc-home/clinical-study-results.html

Clinical Study Results | BAVENCIO® (avelumab) Efficacy Efficacy of BAVENCIO® (avelumab) in clinical studies. See how effective BAVENCIO® (avelumab) is for patients with Merkel cell carcinoma.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.9508

Avelumab (MSB0010718C; anti-PD-L1) in patients with ... Pts received avelumab 10 mg/kg IV Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks ( ...

4. merkelcell.org merkelcell.org/news-and-publications/2025/real-world-safety-and-effectiveness-of-avelumab-in-immune-compromised-ic-and-non-ic-patients-with-merkel-cell-carcinoma-mcc-results-from-a-prospective-german-registry-mcc-trim/

Real-world safety and effectiveness of avelumab in immune ... Results: Among 875 patients with MCC (various disease stages) enrolled in the study, 243 were treated with avelumab, of whom 189 (77.8%) were ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30107762/

Comparative effectiveness of avelumab versus ... Conclusion: This approach merging qualitative and quantitative data suggests that mMCC patients report a better experience with avelumab than with chemotherapy.

6. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2675910

Efficacy and Safety of First-line Avelumab Treatment in ... First-line avelumab monotherapy had antitumor activity and a manageable safety profile in patients with mMCC. Maturing PFS data suggest durable ...