Squamous cell carcinoma is the second most common skin cancer, affecting more than one million Americans each year. Most cases are cured with surgery or radiation, but a small percentage spread to other parts of the body. Advanced disease now has treatment options that didn't exist a decade ago.
What's actually going on in research
Trials are testing checkpoint inhibitors like pembrolizumab and cemiplimab, which help the immune system recognize cancer cells. Researchers are also studying combinations of immunotherapy with targeted drugs, earlier use of these treatments in high-risk local disease, and ways to identify which tumors are most likely to respond. For cutaneous disease, prevention studies are exploring ways to reduce risk in organ transplant recipients and others at high risk.
Checkpoint inhibitors
Drugs like pembrolizumab and cemiplimab block PD-1, allowing T cells to attack cancer. Both are FDA-approved for advanced cutaneous squamous cell carcinoma and are being tested in earlier stages.
Combination strategies
Trials are pairing checkpoint inhibitors with targeted drugs or other immunotherapies to improve response rates. Some are testing whether adding drugs that target specific mutations makes treatment work better.
Adjuvant treatment
Studies are testing whether immunotherapy after surgery can prevent recurrence in high-risk cases. This mirrors approaches that have worked in melanoma and other cancers.
What to know before you search
Eligibility typically depends on whether the cancer has spread, prior treatments, tumor characteristics like size and location, and overall health status.
What types of trials are currently open
- Immunotherapy trials — Testing checkpoint inhibitors alone or in combination for advanced or metastatic disease. Some compare different immunotherapy drugs or test them in earlier stages.
- Targeted therapy trials — Testing drugs aimed at specific mutations found in some squamous cell carcinomas, often in combination with immunotherapy.
- Adjuvant trials — Testing whether treatment after surgery can prevent cancer from coming back in people at high risk of recurrence.
- Prevention trials — Testing ways to prevent new skin cancers in people at high risk, including organ transplant recipients and those with previous skin cancers.
- Radiation trials — Testing different radiation approaches or combinations of radiation with immunotherapy for local or regional disease.
Recently added Squamous Cell Carcinoma trials
Take a new antibody combination for advanced esophageal cancer
This is a prospective, single-center, single-arm Phase II clinical study designed to evaluate the efficacy and safety of sacituzumab tirumotecan in combination with tislelizumab in patients with advanced esophageal squamous cell carcinoma whose disease has progressed following first-line immunotherapy.
Take a new immune therapy combined with chemotherapy for head and neck cancer
This prospective, single-arm, multicenter phase II trial aims to evaluate the efficacy and safety of neoadjuvant beccotatug vedotin combined with pucotenlimab and cisplatin in patients with locally advanced epidermal growth factor receptor (EGFR)-positive head and neck squamous cell carcinoma (HNSCC). A total of 40 treatment-naive patients aged 18-70 years with stage III-IV (AJCC 8th edition) EGFR-positive HNSCC will be enrolled. Participants will receive three 3-week cycles of the triple-drug regimen. Tumor response will be reassessed after cycle 3 using RECIST v1.1. Patients achieving a complete or partial response (CR/PR) may proceed to de-escalation surgery followed by definitive chemoradiotherapy, or to definitive chemoradiotherapy alone; non-responders will undergo radical surgery with or without radiotherapy/chemoradiotherapy, or definitive chemoradiotherapy, as determined by multidisciplinary team (MDT) discussion. The primary endpoint is objective response rate (ORR). Secondary endpoints include major pathological response (MPR), pathological complete response (pCR), disease control rate (DCR), 2-year progression-free survival (PFS), 2-year overall survival (OS), quality of life, and safety. This study aims to provide preliminary evidence on the feasibility and activity of this novel triple combination in the neoadjuvant setting, potentially offering a new treatment paradigm to improve long-term outcomes and reduce recurrence.
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