Tirelizumab in Combination With Carboplatin and Polymeric Micellar Paclitaxel for Neoadjuvant Therapy in cN+ HNSCC

Official title

Prospective, Single-arm, Phase II Clinical Study of Tirellizumab Combined With Carboplatin and Paclitaxel Polymer Micelles Neoadjuvant Therapy for cN+ Head and Neck Squamous Cell Carcinoma

Overview

To explore the efficiency and safety of Tislelizumab combinated with carboplatin and polymeric micellar paclitaxel as a new neoadjuvant treatment regimen for resectable HNSCC patients with clinical positive lymph node metastasis

Detailed description

The 5-year overall survival rate of patients with clinical N-positive head and neck squamous cell carcinoma (HNSCC) is less than 50%, and the clinical outcomes of these patients still need improvement.

Immunotherapy, such as PD-1/PD-L1 inhibitors, has shown excellent efficiency in treating malignant tumors. Anti PD-1 therapy has been approved as a first-line treatment for recurrent/metastatic HNSCC. The results of several phase II clinical trials have shown that neoadjuvant immunotherapy for locally advanced resectable HNSCC has been proven to be safe and feasible. However, immunotherapy has a lower MPR rate for locally advanced HNSCC patients with lymph node metastasis.

Paclitaxel has been used as a first-line induction therapy for locally advanced HNSCC and is an important drug in mediating immunogenic death, enhancing the efficacy of immunotherapy. Previous studies on lung cancer have confirmed that nano-paclitaxel has better induction efficacy than solvent paclitaxel and reduces the rate of distant metastasis.

In summary, the investigators designed this study to explore the efficiency and safety of Tislelizumab combinated with carboplatin and polymeric micellar paclitaxel as a new neoadjuvant treatment regimen for patients with clinical N positive resectable HNSCC, aiming to provide a new treatment option for those patients.

Interventions

• Drug Carboplatin
  Carboplatin AUC 5 on weeks 1, 3, and 6
• Drug Tislelizumab
  Tislelizumab 200 mg on weeks 3, 6, and 9;if adjuvant immunotherapy is omitted, Tislelizumab will be administered on weeks 1, 3, 6, 9, 12, 15 after surgery
• Drug Polymeric Micellar Paclitaxel
  Polymeric Micellar Paclitaxel 300mg/mg/m2 on weeks 1, 3 and 6
• Procedure Surgical Resection of Primary +/- Neck Dissection
  Twenty-eight days (+ 7 days) following the 3rd cycle of neoadjuvant therapy, patients will then undergo definitive surgical resection of the primary site +/- neck dissection(s).
• Radiation Post-operative radiation therapy
  Post-operative radiation therapy +/- radiosensitizing agent(s) will be administered per standard-of-care based on pathologic staging of the surgical specimen. If there is an excellent response to treatment with a high degree of downstaging the addition of adjuvant radiation may be omitted if NCCN guidelines are met. If the pathologic assesment following induction systemic therapy and surgery is ypT(pCR 或 MPR) and ypN(pCR) or ypT（ pCR 或 MPR）and ypN（ MPR）without the presence of Serious Adverse Eve

Primary outcome measures

• Major pathological response (MPR) rate of metastatic lymph nodes [Time frame: 10days after surgery]

Secondary outcome measures (8)

• Major pathological response (MPR) rate of primary tumor [Time frame: 10days after surgery]
• Event-free survival (EFS) [Time frame: 1 years and 3 years]
• Overall survival（OS） [Time frame: 1 years and 3 years]
• Incidence of treatment-related adverse events [Time frame: from the first day of treatment to 30 days after surgery；if adjuvant immotherapy is omitted, time frame is from the first day of treatment to 30 days after last administration]
• EORTC QLQ-C30 [Time frame: from 1 week before treatment to 30 days after surgery]
• pathological downstaging rate [Time frame: 10days after surgery]
• Distant metastasis-free survival(DMFS) rate [Time frame: 1 year and 3 year]
• logical regional-free survival(LRFS) rate [Time frame: 1 year and 3 year]

Eligibility criteria

Inclusion criteria

Males and females ECOG Performance Status 0 or 1. Confirmed pathologic and/or cytologic diagnosis of squamous cell carcinoma of head and neck，T2-4N1-3M0（III-IV）（AJCC 8.0） Histological diagnosis of squamous cell carcinoma of the lip, oral cavity, oropharynx, hypopharynx, larynx.

With measurable target lesions by CT or MRI. Adequate bone marrow function. Adequate renal and liver function. Pregnancy test (for patients of childbearing potential) negative at screening. Signed Written Informed Consent.

Exclusion criteria

Patients who pathologically confirmed non-squamous cell carcinoma Patients who has recurrence or distant metastasis Local lesions have been surgically removed Patients who have received systemic anti-cancer therapy, including hormone therapy Patients who have received treatment targeting PD-1 or PD-L1 Patients with active autoimmune disease or a history of autoimmune disease but may relapse(Patients with the following diseases are not excluded and can be further filtered) Controlled type 1 diabetes Hypothyroidism(If it can be controlled with hormone replacement therapy) Controlled celiac disease Skin diseases that do not require systemic treatment such as Vitiligo, Psoriasis and Hair loss.

Any other disease that is not expected to recur without external triggers Any active malignant tumors within 2 years before treatment, except for the specific cancers being studied in this trial and locally recurring cancers that have been cured (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical in situ Cancer or breast cancer) Any disease requiring systemic treatment with corticosteroids (referring to treatment with a dose higher than 10 mg/day of prednisone or equivalent doses of similar drugs) or other immunosuppressive treatments within 14 days before treatment.

However, patients who have currently or previously used any of the following steroid regimens can be selected:

Adrenaline replacement steroids(Prednisone ≤10mg/day or equivalent dose of similar drugs) Local, ophthalmic, intra-articular, intranasal and inhaled corticosteroids which is Systemic absorbed Minimally Prophylactically short-term (≤7 days) use of corticosteroids (for example, allergy to contrast agents) or for the treatment of non-autoimmune conditions (for example, delayed hypersensitivity reactions caused by contact allergens) Uncontrolled diabetes within 14 days before treatment or laboratory abnormalities with potassium, sodium and corrected calcium levels> 1 after standard drug treatment or hypoalbuminemia grade ≥ 3 History of the following diseases: interstitial lung disease, non-infectious pneumonia or uncontrollable diseases, including pulmonary fibrosis, acute lung disease, etc.

Severe chronic or active infection (including tuberculosis infection, etc.) that required systemic antibiotics, antibacterial or antiviral treatment occurred within 14 days before the first administration of the study drug The patient is known to have been infected with HIV Untreated patients with chronic hepatitis B or HBV carriers with chronic hepatitis B virus (HBV) DNA ≥ 500 IU/mL or active hepatitis C virus carriers (HCV) should be excluded.

Patients can be selected who is Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA <500 IU/mL) and cured hepatitis C patients.

Any surgery requiring general anesthesia has been performed within 28 days before treatment Have had allogeneic stem cell transplantation or organ transplantation

Have any of the following cardiovascular risk factors:

Cardiogenic chest pain within 28 days before treatment(moderate pain that restricts instrumental activities of daily living) Symptomatic pulmonary embolism within 28 days before treatment Acute myocardial infarction within 6 months before treatment Any history of heart failure that has reached Grade III or IV as defined by the New York Heart Association within 6 months before treatment Grade 2 ventricular arrhythmia within 6 months before the first administration of the study drug Have a history of cerebrovascular accident within 6 months before the first administration of the study drug Have a history of severe hypersensitivity to other monoclonal antibodies Patients with treatment toxicity (caused by previous anti-cancer treatments) have not returned to baseline or stabilized, unless it is an AE that is not considered a possible safety risk (such as hair loss, neuropathy, or specific laboratory abnormalities) History of allergic reactions to cisplatin or other platinum-containing compounds Peripheral nerve disease ≥ Grade 2 defined by NCI CTCAE v5.0 standard Have gotten a live vaccine within 4 weeks before treatment(Seasonal flu vaccines are usually inactivated vaccines and are allowed to be used; The vaccine used in the nasal cavity is a live vaccine and is not allowed to be used) Abuse or dependence on alcohol or drugs and Basic medical conditions (including laboratory abnormalities) that are not conducive to the administration of the study drug , affect the interpretation of drug toxicity or AEs, lead to insufficient compliance with the study execution and possible damage The patient participates in another therapeutic clinical study at the same time

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06366945 · SYSKY-2024-157-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗