Where advanced skin squamous cell cancer treatment is heading

Cutaneous squamous cell carcinoma is the second most common skin cancer, with over a million cases a year in the US. Almost all are cured by simple removal, but several thousand become high-risk, locally advanced or metastatic each year, especially on the head and neck, in older adults, and in organ-transplant recipients. For these, PD-1 immunotherapy has transformed care: it is now the first treatment for advanced disease, is approved after surgery, and is being tested before surgery to avoid disfigurement.

• 92studies open or running
• 8phase 3 trials
• 582papers published this year
• 40NIH-funded projects

1. Now

   Nov 2026

   Immunotherapy after surgeryHappened 87.1% disease-free at 2 years

   Cemiplimab: 87.1% disease-free at 2 years vs 64.1% with placebo. FDA approved October 2025.

   87.1%: disease-free at 24 months, vs 64.1% with placebo.

   • C-POST trial

   Immunotherapy before surgeryHappened 63% complete response

   Pembrolizumab cleared cancer in 63%; nearly half avoided surgery and radiation altogether.

   63%: clinical or pathologic complete response.

   • Neoadjuvant pembrolizumab de-escalation study

   Lasting responses in advanced diseaseHappened 47.2% response rate

   Cemiplimab: 47.2% response rate, median progression-free survival 26 months.

   47.2%: response rate.

   • EMPOWER-CSCC-1 long-term results

2. 6 months

   by May 2027

   Combinations for advanced diseasePossible 11.1 mo progression-free

   Avelumab plus cetuximab gave median progression-free survival of 11.1 vs 3.0 months; larger trials may follow.

   11.1 mo: median progression-free survival, vs 3.0 months with avelumab alone.

   • Alliance A091802 trial

3. 12 months

   by Nov 2027

   Radiation plus immunotherapyPossible

   A Memorial Sloan Kettering study tests combining radiation with cemiplimab; due October 2027.

   • MSK radiation-cemiplimab study

4. 3 years

   by late 2029

   Options for transplant recipientsLong shot

   Replimune's RP1, a tumor-injected virus, is tested in organ-transplant recipients who usually cannot have immunotherapy; due July 2029.

   • RP1 transplant trial

   Injected immune drugsLong shot

   Philogen's L19IL2/L19TNF, injected into tumors, is in a 92-person trial; due February 2031.

   • L19IL2/L19TNF trial

5. 5 years

   by late 2031

   Injecting immunotherapy instead of surgeryPossible

   Regeneron's phase 3 (369 people) tests cemiplimab injected into early-stage tumors; due May 2030.

   • Intralesional cemiplimab trial

   Who needs radiation after surgeryLong shot

   SPINO-RT (266 people) compares routine radiation with a monitoring-based approach; due June 2031.

   • SPINO-RT

The research paths

Borrowed from other cancers

Open to join now

• Early-stage cSCC

  Intralesional cemiplimab

  Phase 3 · 53 sites

  Locations and eligibility →

• High-risk cSCC

  Radiation vs monitoring after surgery

  Phase 3 · 28 sites

  Locations and eligibility →

• cSCC

  L19IL2/L19TNF

  Phase 2 · 19 sites

  Locations and eligibility →

See every recruiting Skin squamous cell cancer trial →

When the trials finish

Completion dates the trials registered. Results usually follow 3 to 12 months later.

What just happened

Standard treatment today

• Low-riskSurgical removal or Mohs surgery; cure rates are very high.
• High-risk, removableSurgery, often radiation; cemiplimab afterward for the highest risk.
• Locally advanced or metastaticCemiplimab or pembrolizumab; cetuximab-based treatment if immunotherapy is unsuitable.
• Organ-transplant recipientsReduce immunosuppression where possible; immunotherapy carries rejection risk.

See Skin squamous cell cancer trials recruiting now →