Squamous cell carcinoma (SCC) arises from flat skin cells and can develop on sun-exposed skin, inside the mouth and throat, in the lungs, and at other sites — making it one of the most common cancer types worldwide. While most skin SCCs are cured by surgery, advanced or metastatic SCC has historically been difficult to treat.
What's actually going on in research
Immune checkpoint inhibitors targeting PD-1 have become standard for advanced cutaneous SCC and are being tested across other SCC subtypes, including those driven by HPV. Antibody-drug conjugates are being developed for SCC expressing specific surface proteins, offering targeted delivery of chemotherapy. For locally advanced disease, combination approaches pairing immunotherapy with radiation are being tested to see if the immune response can prevent distant spread.
PD-1 checkpoint inhibitors
Drugs blocking PD-1 have shown durable responses in advanced skin SCC and are now being tested in earlier-stage disease, in combination with surgery, and across other SCC sites.
Antibody-drug conjugates
Targeted delivery drugs that recognize proteins overexpressed on squamous cells are in trials for patients who have progressed on immunotherapy.
Radiation-immunotherapy combinations
Combining radiation — which can expose tumor antigens — with checkpoint inhibitors is being tested to create a systemic immune response that controls distant disease.
What to know before you search
Eligibility depends on tumor site (skin, head and neck, lung, etc.), stage, PD-L1 expression, prior treatments, and performance status.
What types of trials are currently open
- Treatment trials — Testing immunotherapy, targeted drugs, or new chemotherapy combinations in advanced or metastatic SCC.
- Adjuvant trials — Testing post-surgery drug treatments to prevent recurrence in high-risk resected SCC.
- Neoadjuvant trials — Testing treatments before surgery to shrink tumors and assess response.
- Prevention trials — Evaluating sun-protective strategies, field therapies, and chemoprevention in high-risk individuals.
- Supportive care trials — Managing immune-related side effects and treatment-related skin reactions.
Recently added Squamous Cell Carcinoma trials
Trial Evaluating Hypo-fractionated Accelerated Versus Conventional Fractionated Adjuvant RT in Head & Neck Malignancies
Hypo-fractionated radiotherapy reduces the OTT (overall treatment time) which may in turn reduce rapid accelerated repopulation of clonogenic cells during waiting period after surgery. If this holds true, there is a potential to achieve better loco-regional control in with PORT for HNSCC. There is a strong radiobiological and economic rationale for delivery hypo-fractionated radiotherapy in HNSCC. The HYPCON III trial will be aimed to reduce the number of fractions by 50% (30 fr to 15 fr)
Induction Chemo-Immunotherapy + Radiotherapy vs Concurrent Chemoradiotherapy for Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma
This is a prospective, randomized, phase II clinical study in patients with unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC). Eligible patients will be randomly assigned in a 1:1 ratio to two treatment groups. The experimental group will receive 3 cycles of induction therapy with PD-1 antibody plus chemotherapy, followed by radiotherapy, and then maintenance therapy with PD-1 antibody monotherapy. The control group will receive concurrent chemoradiotherapy, followed by maintenance therapy with PD-1 antibody monotherapy. The primary endpoints are the complete response (CR) rate at 3 months after radiotherapy (assessed by investigators) and the 1-year progression-free survival (PFS) rate. Secondary endpoints include overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), quality of life, and safety profile.
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