A Study Testing Emactinib Sulfate With Chemotherapy and Immunotherapy Before Surgery for Advanced Head and Neck Cancer

NCT07457346 | Recruiting Phase 2

• 1 other identifier: Y2025-0723
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of a novel combination therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). The therapy combines the JAK1 inhibitor Sulfamethoxazole, the anti-PD-L1 antibody Adebrelimab, and chemotherapy (Nab-paclitaxel + Cisplatin) as a neoadjuvant treatment (given before surgery). The main questions it aims to answer are:

• For patients with resectable locally advanced HNSCC: Can this combination improve the pathological complete response (pCR) rate (the absence of viable cancer cells in the surgical specimen) compared to current neoadjuvant therapies?
• For patients with potentially resectable or unresectable locally advanced HNSCC: Can this combination improve the objective response rate (ORR) (the percentage of patients with significant tumor shrinkage), potentially making surgery possible or reducing its scope? Researchers will also assess secondary outcomes including event-free survival (EFS), overall survival (OS), and the safety profile of the combination. Participants will:
• Receive neoadjuvant treatment with the combination of Sulfamethoxazole, Adebrelimab, and chemotherapy. A key feature is the timed sequencing of the JAK inhibitor, which will be started on day 8 of each treatment cycle.
• Be evaluated for surgery after the neoadjuvant treatment. For those who undergo surgery, the pathological response will be analyzed.
• Have regular follow-up assessments, including imaging studies (such as CT or MRI scans) and safety monitoring, to evaluate long-term treatment response, survival, and side effects.
• Provide tissue and/or blood samples for exploratory biomarker analysis (e.g., Interferon-Stimulated Gene signature) to help identify patients who benefit most from this treatment.

Conditions

Head and Neck Cancer Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Pathological Complete Response (pCR) Rate in Cohort A (Resectable)

  The proportion of participants in Cohort A (resectable locally advanced HNSCC) who achieve a pathological complete response (pCR) upon histopathological examination of the surgical resection specimen after 2 cycles of neoadjuvant therapy. pCR is defined as the absence of viable tumor cells (ypT0 ypN0) as per College of American Pathologists (CAP) criteria.

  approximately 12-14 weeks from the start of treatment

• Objective Response Rate (ORR) in Cohort B (Potentially Resectable)

  The proportion of participants in Cohort B (potentially resectable locally advanced HNSCC) who achieve a best overall response of Complete Response (CR) or Partial Response (PR) according to RECIST 1.1 criteria, assessed via imaging (CT/MRI) after 2 cycles of neoadjuvant therapy.

  approximately 6 weeks from the start of treatment

• Objective Response Rate (ORR) in Cohort C (Unresectable)

  The proportion of participants in Cohort C (unresectable locally advanced HNSCC) who achieve a best overall response of Complete Response (CR) or Partial Response (PR) according to RECIST 1.1 criteria, assessed via imaging (CT/MRI) after 2 cycles of neoadjuvant therapy.

  approximately 6 weeks from the start of treatment

Secondary Outcomes (3)

• Event-Free Survival (EFS)

  assessed up to 3 years.

• Overall Survival (OS)

  assessed up to 3 years.

• Incidence of Treatment-Related Adverse Events (TRAEs)

  From the first dose of study treatment until 90 days after the last dose. Continuous monitoring throughout the study, expected to be approximately 6 months for the neoadjuvant and definitive therapy phases, plus the 90-day safety follow-up.

Study Arms (1)

Neoadjuvant treatment (chemotherapy+immunotherapy+JAKi)

EXPERIMENTAL

Patients are stratified into three cohorts based on resectability status: Cohort A (Resectable) + Cohort B (Potentially Resectable) + Cohort C (Unresectable) All enrolled patients receive the same neoadjuvant therapy.

Drug: cisplatin+ nab-paclitaxel +adebrelimab + imaxitinib

Interventions

cisplatin+ nab-paclitaxel +adebrelimab + imaxitinib DRUG

Treatment is administered in 21-day cycles, with a response assessment after 2 cycles. On Day 1 of each cycle, patients receive cisplatin (60mg/m²) plus nab-paclitaxel (260mg/m²) concurrently with adebrelimab (1200mg). Starting from Day 8 through Day 21 of each cycle, patients orally take 4mg of imaxitinib daily.

Neoadjuvant treatment (chemotherapy+immunotherapy+JAKi)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG Performance Status of 0-1.
• Histologically and/or cytologically confirmed Stage III-IVA head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, or larynx).
• 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).
• Biomarker: Peripheral blood flow cytometry analysis showing that PD-1+TIM-3+CD8+ exhausted T cells account for \>10% of CD8+ T cells.
• 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.
• 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.

You may not qualify if:

• 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.
• Active autoimmune disease or condition requiring immunosuppressive therapy. Subjects requiring systemic corticosteroids or other immunosuppressive drugs prior to enrollment.
• History of other active malignancies or active infections (including tuberculosis and hepatitis); uncontrolled infections (HIV, HBV, HCV).
• 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.
• Pregnant or lactating women. Subjects unwilling to use effective contraception during the study period.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

2nd Affiliated Hospital, School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

Central Study Contacts

Ting Zhang, phD.

CONTACT

+8657187783521; zezht@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients are stratified into three cohorts based on resectability status: Cohort A (Resectable)+Cohort B (Potentially Resectable)+ Cohort C (Unresectable). All enrolled patients receive the same neoadjuvant therapy.

Study Record Dates

• First Submitted: March 4, 2026
• First Posted: March 9, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): August 30, 2030
• Last Updated: March 9, 2026

Record last verified: 2025-09

Locations

CN (1)