565 HNSCC Clinical Trials Recruiting Now (May 2026): Head and Neck Squamous Cell Carcinoma — IO, Petosemtamab, ADC, HPV+

Last updated: May 27, 2026

Current Clinical Trial Landscape

Active research areas in 2026:

Neoadjuvant/perioperative immunotherapy (KEYNOTE-689 practice-changing: pembrolizumab before + after surgery)
Bispecific antibodies: petosemtamab (EGFR×LGR5), ficerafusp alfa (TGFβ×PD-L1)
ADCs: becotatug vedotin (MRG003, EGFR-ADC) — multiple Phase 3 trials
De-intensification for HPV-positive oropharyngeal cancer
Novel IO combinations: ivonescimab (PD-1×VEGF), volrustomig (PD-1×CTLA-4)

Standard of care: Locally advanced: concurrent chemoRT (cisplatin) or cetuximab+RT. Recurrent/metastatic: pembrolizumab ± chemotherapy (KEYNOTE-048) for PD-L1 CPS ≥1. Second-line: nivolumab, cetuximab combinations. HPV/p16 status is a key prognostic and trial eligibility factor.

Recruiting Trials by Treatment Setting

Neoadjuvant / Perioperative (Before and After Surgery)

Following KEYNOTE-689 results, perioperative immunotherapy is rapidly expanding:

- NCT07371611 - Sintilimab + chemo as neoadjuvant and adjuvant for LA-HNSCC (Phase 3)

Locally Advanced — Definitive Chemoradiation

Concurrent chemoRT with cisplatin or cetuximab remains standard. Trials test IO additions and de-intensification:

IO + chemoRT:
- NCT06129864 - Volrustomig (PD-1×CTLA-4) for unresected LA-HNSCC (Phase 3)
- NCT07445048 - Postoperative RT + nimotuzumab + benmelstobart in high-risk HNSCC (Phase 3)
- NCT04892173 - NBTXR3 nanoparticles + RT ± cetuximab in platinum-ineligible LA-HNSCC (Phase 3)
De-intensification (HPV-positive):
- NCT06030440 - De-intensified postoperative RT in HPV+ HNSCC (Phase 3)

Recurrent or Metastatic — First-Line

Pembrolizumab ± chemo (KEYNOTE-048) is standard. Trials test novel IO combinations and bispecifics:

Bispecific antibodies:
- NCT06525220 - Petosemtamab (EGFR×LGR5) + pembrolizumab vs pembrolizumab in first-line R/M HNSCC (Phase 3)
- NCT06788990 - FORTIFI-HN01: Ficerafusp alfa (TGFβ×PD-L1) + pembrolizumab vs placebo + pembrolizumab (Phase 3)
Novel IO combinations:
- NCT07264075 - Ivonescimab (PD-1×VEGF) ± ligufalimab vs standard in R/M HNSCC (Phase 3)
- NCT07276399 - Amivantamab + SOC vs SOC in R/M HNSCC (Phase 3)

Recurrent or Metastatic — Second-Line and Beyond

After checkpoint failure, ADCs and cetuximab combinations offer new options:

ADCs:
- NCT07524452 - Becotatug vedotin (MRG003) + PD-1 vs PD-1 alone in R/M HNSCC (Phase 3)
- NCT06496178 - Petosemtamab vs investigator's choice in post-IO R/M HNSCC (Phase 3)
Cetuximab combinations:
- NCT06064877 - Ficlatuzumab + cetuximab in cetuximab-resistant R/M HNSCC (Phase 3)
Re-irradiation:
- NCT07026474 - Re-radiochemo + pembrolizumab vs immuno(chemo)therapy for locoregionally recurrent HNSCC (Phase 3)

Showing selected notable trials. View all 565 recruiting HNSCC interventional trials on ClinicalTrials.gov.

Frequently Asked Questions

How do I find head and neck cancer clinical trials I'm eligible for?

Enter your HNSCC details into ClinTrialFinder — including HPV/p16 status, PD-L1 CPS score, tumor subsite (oral cavity, oropharynx, larynx, hypopharynx), and prior treatments. The AI matches you with trials based on your specific profile in minutes.

What head and neck cancer trials are currently recruiting?

There are 565 recruiting interventional HNSCC (head and neck squamous cell carcinoma) trials as of May 2026, including checkpoint immunotherapy, cetuximab combinations, ADCs, bispecific antibodies, and neoadjuvant immunotherapy before surgery.

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