Neoadjuvant Chemotherapy and Programmed Cell Death Protein 1(PD-1) Inhibition for Head and Neck Cancer Treatment De-escalation (NeoScorch HN)

NCT07209189 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J2537IRB00490896
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The NeoScorch HN study is a single institution multisite phase II trial including 3 cohorts of 25 patients each for patients with newly diagnosed locoregionally advanced, histologically confirmed, head and neck cancer eligible for curative-intent treatment, who will receive neo-adjuvant chemoimmunotherapy-based treatment as well as standard of care adjuvant treatment. The three cohorts include three different aspects of surgical de-escalation in head and neck cancer. The first cohort includes human papillomavirus independent (HPV-) squamous cell carcinoma of the head and neck. The second cohort includes HPV-associated head and neck cancer with radiographic evidence of extranodal extension in neck lymphadenopathy. The third cohort specifically includes malignancies of the sinonasal cavity and skull base which have a propensity for invasion of the orbit, skull base, and maxilla. Surgical treatment of all three of these cohorts has significant morbidity including swallowing, speech, and vision among others.

Conditions

Head and Neck Cancer; Squamous Cell Carcinoma; Oral Cavity Cancer; Oropharyngeal Cancer; Laryngeal Cancer; Sinonasal Squamous Cell Carcinoma; HPV (Human Papillomavirus)-Associated Carcinoma; Skull Base Tumors; HPV 16 Positive Oropharyngeal Tumors (OPC)

Keywords

head and neck cancer; oral cancer; oropharyngeal cancer; laryngeal cancer; HPV associated; squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR)

  The objective is to achieve high-quality or "deep" responses to treatment (measurable pathologic response, MPR) that are sufficient to enable surgical de-escalation (less extensive surgery) or response-adaptive, function-preserving surgery (tailoring the surgical approach to preserve organ structure and function while maintaining oncologic safety).

  Up to 5 years

Study Arms (3)

Neo + Surg : Neoadjuvant Treatment and surgery

EXPERIMENTAL

Neoadjuvant Chemotherapy with * Toripalimab + Cisplatin + Docetaxel OR * Toripalimab + Carboplatin + Docetaxel

Drug: Toripalimab + Chemotherapy

Rad+/-Chem : Adjuvant radiation or chemoradiotherapy

EXPERIMENTAL

Radiation or Chemotherapy will be given after the surgery

Radiation: Chemoradiotherapy or radiation

Adjuvant (ADJ) treatment

EXPERIMENTAL

Treated with Toripalimab after adjuvant treatment

Drug: Toripalimab

Interventions

Toripalimab + Chemotherapy DRUG

Toripalimab is the study drug and will be given via IV in all arms except "Rad+/-Chem : Adjuvant radiation or chemoradiotherapy"

Also known as: Cisplatin, Carboplatin, Docetaxel

Neo + Surg : Neoadjuvant Treatment and surgery

Toripalimab DRUG

Study drug

Adjuvant (ADJ) treatment

Chemoradiotherapy or radiation RADIATION

In the adjuvant phase, either radiation or chemoradiotherapy is used for treatment

Rad+/-Chem : Adjuvant radiation or chemoradiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects must have histologically confirmed, locoregionally advanced head and neck or sinonasal, nasolacrimal, or skull base tumors and meet HPV testing requirements as outlined.
• HPV-independent HNSCC (cT2-cT4, N0-N3) with potential for organ preservation using response-adapted surgery.
• HPV-associated HNSCC with radiographic extranodal extension (cT1-cT3 tonsil or lateralized base of tongue, N0-N1, up to 4 nodes with rENE).
• Sinonasal/skull base tumors, including: sinonasal carcinomas, HPV-associated sinonasal cancer, sinonasal undifferentiated carcinoma (e.g., Isocitrate dehydrogenase 2 (IDH2) mutant), or neuroendocrine sinonasal tumors (e.g., olfactory neuroblastoma) (cT2-cT4, N0-N3).
• HPV16 type only. Patients with non-HPV16 cancers are not eligible. If p16 immunohistohemistry (IHC) positivity is the only result available at enrollment, neoadjuvant therapy may start while HPV nucleic acid testing is pending. Patients found to be HPV non-16 must discontinue study participation.
• At least 8 unstained 5-µm slides must be available. If unavailable, a new biopsy is required unless waived by the PI.
• Appropriate candidates for curative-intent therapy.
• American Joint Committee on Cancer (AJCC) 7th edition: Stage III-IV, excluding N2c or bulky N2b/c (N3 equivalent) and bulky T4 (≥30cc).
• AJCC 8th edition: Stage I with N1, Stage II, or Stage III, excluding N2 disease, bulky nodal disease (N3 equivalent), or bulky T4 (≥30cc).
• Surgical arm: Candidates must be operable based on upfront imaging/exam. Patients with Grade 1 rENE may proceed to surgery; Grade 2/3 rENE are excluded.
• Measurable disease per RECIST 1.1.
• No prior systemic therapy, radiotherapy, or investigational agents for the current cancer.
• No complete surgical resection within 8 weeks of enrollment (biopsy or excision with residual disease acceptable).
• Eastern Cooperative Oncology Group (ECOG) 0-1 or Karnofsky ≥70%.
• Platelets ≥100,000/µL.

You may not qualify if:

• WOCBP with a positive urine pregnancy test within 72 hours before treatment allocation; if positive or inconclusive, a confirmatory serum pregnancy test is required.
• Pregnant or breastfeeding, or planning to conceive or father a child during the study and for 120 days after the last dose.
• Prior treatment with PD-1, PD-L1, PD-L2 inhibitors, or other agents targeting T-cell receptors (e.g., Cytotoxic T-lymphocyte antigen 4 (CTLA-4), OX40 (Tumor Necrosis Factor Receptor Superfamily Member 4), CD137).
• Prior systemic anti-cancer therapy or radiotherapy for the current cancer. Surgery is allowed if adequately recovered from complications.
• Radiotherapy within 2 weeks of study start. A 1-week washout is permitted for palliative, non-stereotactic radiation (≤2 weeks) to non-Central Nervous System (CNS), non-head and neck disease, provided there are no residual toxicities, no steroid requirement, and no history of radiation pneumonitis.
• Live or live-attenuated vaccines within 30 days of first study dose (including live Corona Virus Disease (COVID-19) vaccines). Inactivated, Messenger ribonucleic acid (mRNA), and peptide vaccines are allowed.
• Concurrent treatment with other investigational agents.
• Participation in another investigational drug or device study within 4 weeks before first study dose, unless in follow-up phase only.
• Diagnosis of immunodeficiency, or receiving chronic systemic steroids at doses \>10 mg prednisone equivalent daily, or other immunosuppressive therapy within 7 days before study drug.
• Active autoimmune disease requiring systemic treatment in the past 2 years. Physiologic replacement therapy (thyroxine, insulin, low-dose steroids for adrenal or pituitary insufficiency) is allowed.
• History of severe hypersensitivity (≥Grade 3) to Toripalimab, its excipients, or other anti-PD-1 agents.
• Additional active malignancy requiring treatment within 2 years, except basal/squamous cell skin cancers, in situ cancers, low-grade tumors unlikely to affect survival within 3 years, or cancers treated with curative therapy.
• Active CNS metastases or carcinomatous meningitis. Intracranial extension of the primary tumor is allowed. Patients with previously treated brain metastases may enroll if radiologically stable ≥4 weeks, clinically stable, and off steroids ≥14 days before study drug.
• History of pneumonitis or interstitial lung disease requiring steroids, or current pneumonitis/Interstitial Lung Disease (ILD).
• Active infection requiring systemic therapy.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Coherus Oncology, Inc.: collaborator

Study Sites (1)

Johns Hopkins Hospital East Baltimore

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell; Mouth Neoplasms; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Papillomavirus Infections

Interventions

toripalimab; Drug Therapy; Cisplatin; Carboplatin; Docetaxel; Chemoradiotherapy; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Combined Modality Therapy; Radiotherapy; Physical Phenomena

Study Officials

• Nyall R London, MD, Ph.D

  Otolaryngology - Broadway

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zubair Khan, MBBS, MPH

CONTACT

4109553157; ototrials@live.johnshopkins.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2025
• First Posted: October 6, 2025
• Study Start: February 18, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)