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

Last updated: July 1, 2026

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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)
- NCT06563479 - Personalized RT vs standard RT in HPV-positive oropharyngeal SCC (Phase 3, activated 2026-06-04 — risk-adapted RT dose personalization strategy for the favorable-biology HPV+ subset)
Surgical / RT-field decision (early-stage + lateralized):
- NCT04333537 - Sentinel lymph node (SLN) biopsy vs standard neck dissection for early-stage oral cavity SCC (Phase 2/3, activated 2026-06-26 — surgical-morbidity-reduction strategy to spare comprehensive neck dissection in clinically node-negative cT1-2N0 disease)
- NCT05451004 - SPECT-CT-guided elective contralateral neck treatment in lateralized oropharyngeal cancer (Phase 3, activated 2026-06-10 — imaging-guided personalization of contralateral neck RT/dissection based on lymphatic drainage mapping)

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)
- NCT06589804 - Cetuximab + pembrolizumab for recurrent HNSCC after prior anti-PD-1 (Phase 3, post-IO cetuximab combination)
Re-irradiation:
- NCT07026474 - Re-radiochemo + pembrolizumab vs immuno(chemo)therapy for locoregionally recurrent HNSCC (Phase 3)

Showing selected notable trials. View all 568 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 568 recruiting interventional HNSCC trials in July 2026 including 50 Phase 3 studies. Active classes: checkpoint immunotherapy (KEYNOTE-689 perioperative pembrolizumab practice-changing), bispecific antibodies (petosemtamab EGFR×LGR5, ficerafusp alfa TGFβ×PD-L1, ivonescimab PD-1×VEGF, volrustomig PD-1×CTLA-4 — see bispec IO hub), EGFR amivantamab NCT07276399, cetuximab combinations (ficlatuzumab NCT06064877, cetuximab + pembro NCT06589804 post-IO), ADCs (becotatug vedotin MRG003 NCT07524452, petosemtamab post-IO NCT06496178), and neoadjuvant immunotherapy.

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