Emactinib sulfate with chemotherapy and adebrelimab given before surgery for advanced head and neck cancer

A Pilot Trial of Neoadjuvant Sulfate Emactinib Plus Chemo-immunotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck.

This trial tests whether giving emactinib plus adebrelimab with nab‑paclitaxel and cisplatin before surgery can shrink tumors or increase complete responses in people with locally advanced head and neck squamous cell carcinoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 76 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (other)
• Drugs / interventions: immunotherapy, Adebrelimab, chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07457346 on ClinicalTrials.gov

What this trial studies

This is a phase 2 neoadjuvant trial combining a JAK1 inhibitor (emactinib/imaxitinib), the anti‑PD‑L1 antibody adebrelimab, and chemotherapy (nab‑paclitaxel plus cisplatin) administered before planned surgery. Patients are enrolled across cohorts defined as resectable, potentially resectable, or unresectable locally advanced HNSCC to measure both pathological complete response (pCR) in resectable cases and objective response rate (ORR) in potentially/unresectable cases. Key secondary outcomes include event‑free survival (EFS), overall survival (OS), and safety/tolerability of the combination. The trial is conducted at the Second Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou and uses imaging and surgical pathology to determine responses.

Who should consider this trial

Good fit: Adults with histologically confirmed stage III–IVA head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, or larynx) with ECOG 0–1 who meet cohort criteria for resectable, potentially resectable, or unresectable disease are the intended participants.

Not a fit: Patients with poor performance status, widespread metastatic disease, major organ dysfunction, or contraindications to the study drugs or planned surgery are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could raise pCR and ORR rates, potentially allowing less extensive surgery or converting some unresectable tumors into operable ones.

How similar studies have performed: Neoadjuvant chemotherapy plus immune checkpoint inhibitors has shown improved pCR rates in some HNSCC studies, but combining a JAK1 inhibitor with PD‑L1 blockade and chemotherapy is a newer approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. ECOG Performance Status of 0-1.
2. Histologically and/or cytologically confirmed Stage III-IVA head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, or larynx).
3. Classified according to the Asia-Pacific multidisciplinary consensus (Y.Guo et al., Oral Oncol 2024):

   * Cohort A: Resectable\*\* (amenable to upfront surgery): T2N2-3M0, T3-4N0-2M0 (AJCC 8th edition).
   * Cohort B: Potentially Resectable:\*\* Cases with relative contraindications to surgery (e.g., cervical lesion directly invading skin, anterior 2/3 tongue tumor extending below the hyoid level, extension to the vallecula) or where surgery would cause significant disfigurement/functional loss, requiring discussion by an MDT (head \& neck surgery, radiology) to weigh risks vs. non-surgical options.
   * Cohort C: Unresectable: Tumor extensively invading skull base, extending to nasopharynx/deep nasopharyngeal wall, invading/encasing carotid artery, extending to mediastinal structures, prevertebral fascia, or cervical spine; T3-4 (N0-3) or any N2a-3 (T1-4) M0 (AJCC 8th edition).
4. Biomarker: Peripheral blood flow cytometry analysis showing that PD-1+TIM-3+CD8+ exhausted T cells account for \>10% of CD8+ T cells.
5. Adequate baseline organ function within 14 days prior to enrollment:

   * Hematological: White Blood Cell count (WBC) ≥4000/μL, Absolute Neutrophil Count (ANC) ≥2000/μL, Hemoglobin (HGB) ≥9 g/dL, Platelet count (PLT) ≥100,000/μL.
   * Renal: Serum creatinine \<1.5 times the Upper Limit of Normal (ULN) OR Creatinine Clearance (CrCl) \>60 mL/min (calculated by Cockcroft-Gault formula).
   * Hepatic: Total bilirubin ≤1.5x ULN (except subjects with Gilbert's syndrome, who may have total bilirubin \<3x ULN); Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) ≤3x ULN; Alkaline Phosphatase (ALP) ≤3x ULN; Albumin (ALB) ≥3 g/dL.
6. Ability to understand and willingness to sign the Informed Consent Form. Subjects must be willing and able to comply with the protocol, including receiving treatments and scheduled visits/examinations, including follow-up.

Exclusion Criteria:

1. Prior treatment with immunotherapy (anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 agents) or JAK inhibitors. History of severe allergic reactions to any component of monoclonal antibodies.
2. Active autoimmune disease or condition requiring immunosuppressive therapy. Subjects requiring systemic corticosteroids or other immunosuppressive drugs prior to enrollment.
3. History of other active malignancies or active infections (including tuberculosis and hepatitis); uncontrolled infections (HIV, HBV, HCV).
4. Severe cardiac or pulmonary dysfunction, including severe cardiac insufficiency (e.g., NYHA Class III or higher) or severe pulmonary dysfunction (e.g., FEV1 \<50% predicted); history of thrombotic diseases, coagulation disorders (Prothrombin Time (PT) \>16 seconds, Activated Partial Thromboplastin Time (APTT) \>53 seconds, Thrombin Time (TT) \>21 seconds, Fibrinogen (FIB) \<1.5 g/L), bleeding tendency, or current thrombolytic/anticoagulant therapy.
5. Pregnant or lactating women. Subjects unwilling to use effective contraception during the study period.

Where this trial is running

Hangzhou, Zhejiang

• 2nd Affiliated Hospital, School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Ting Zhang, phD.

Conditions: Head and Neck Cancer Squamous Cell Carcinoma