Comparing two and four courses of pembrolizumab with chemotherapy for head and neck cancer

Safety and Efficacy of Four Courses of Pembrolizumab Combined With Carboplatin and Albumin-binding Paclitaxel Versus Two Courses of Neoadjuvant Therapy in Patients With Resectable Head and Neck Squamous Cell Carcinoma (T3 or T4, N0) : An Optimal Efficacy Study (Prospective, Two-arm, Phase II)

This study is testing whether getting two or four rounds of a new cancer drug along with chemotherapy helps people with head and neck cancer do better before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 192 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: Pabolizumab, chemotherapy, prednisone, pembrolizumab, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05980702 on ClinicalTrials.gov

What this trial studies

This clinical trial involves 200 patients with resectable head and neck squamous cell carcinoma (HNSCC) who will receive either two or four courses of pembrolizumab, a PD-1 inhibitor, combined with carboplatin and albumin-binding paclitaxel as neoadjuvant therapy. Patients are randomly assigned to one of the two treatment groups, and their imaging and pathological changes will be monitored before and after treatment. The study aims to evaluate the safety and efficacy of the different treatment durations by assessing the pathological complete response (pCR) rates. Clinical data, including pathological grade, stage, and prognosis, will be collected to determine the optimal treatment approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with resectable T3 or T4, N0 head and neck squamous cell carcinoma who have not received prior systemic antitumor therapy.

Not a fit: Patients with advanced metastatic disease or those who have previously undergone extensive chemotherapy or radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve treatment outcomes for patients with resectable head and neck squamous cell carcinoma.

How similar studies have performed: Other studies have shown promising results with PD-1 inhibitors in combination with chemotherapy for similar conditions, suggesting this approach may be effective.

Eligibility criteria

Inclusion Criteria:

* 18 years of age ≤65 years of age;
* cytological or histological diagnosis of surgically resectable head and neck squamous cell carcinoma with the following stages: T3 or T4, N0;
* According to the solid tumor efficacy evaluation criteria (RECIST version 1.1), there was at least one radiologically measurable lesion; First-line patients: have not previously received any systemic antitumor therapy for advanced/metastatic disease. Patients who had previously received platinum-containing adjuvant/neoadjuvant chemotherapy, or had received radical chemoradiotherapy for advanced disease, if the interval between disease progression or recurrence and the end of the last chemotherapy drug treatment was at least 6 months, were allowed to be enrolled in this study.
* ECOG score 0-1;
* Expected survival time \> 3 months;
* Adequate organ function, subject shall meet the following laboratory indicators:

  1. The absolute value of neutrophil granulocyte (ANC) ≥1.5x109/L in the last 14 days without the use of granulocyte colony stimulating factor;
  2. Platelets ≥100×109/L without blood transfusion in the past 14 days;
  3. Hemoglobin \&gt without blood transfusion or use of erythropoietin within the last 14 days; 9g/dL;
  4. Total bilirubin ≤1.5× upper limit of normal value (ULN);
  5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (ALT or AST ≤5×ULN in patients with liver metastasis);
  6. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 ml/min;
  7. Good coagulation function, defined as International Standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN;
  8. Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. Subjects whose baseline TSH is outside the normal range can be enrolled if total T3 (or FT3) and FT4 are within the normal range;
  9. The myocardial enzyme profile was within the normal range (if the researchers comprehensively judged that the simple laboratory abnormality was not clinically significant, it was also allowed to be included);
  10. For female subjects of childbearing age, a urine or serum pregnancy test should be tested negative within 3 days prior to receiving the first study drug administration (day 1 of Cycle 1). If the urine pregnancy test results cannot be confirmed negative, a blood pregnancy test is requested. Women of non-reproductive age were defined as at least one year after menopause or having undergone surgical sterilization or hysterectomy;
  11. If there is a risk of conception, all subjects (male or female) shall use contraception with an annual failure rate of less than 1% for the entire duration of treatment up to 120 days after the last study drug administration (or 180 days after the last chemotherapeutic drug administration).

Exclusion Criteria:

* Malignant diseases other than head and neck squamous cell carcinoma diagnosed within 5 years prior to initial administration (excluding basal cell carcinoma of the skin after radical treatment, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after radical excision);
* Currently participating in an interventional clinical study, or receiving other investigational drugs or using investigational devices within 4 weeks prior to initial dosing;
* Previous treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulus or synergistic inhibition of T cell receptors (e.g., CTLA-4, OX-40, CD137);
* Systemic treatment with Chinese patent drugs or immunomodulatory drugs (including thymosin, interferon and interleukin, except for local use to control pleural effusion) with indications of anti-head and neck squamous cell carcinoma within 2 weeks before the first administration;
* An active autoimmune immune disease requiring systemic treatment (e.g. with disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within 2 years prior to initial administration. Alternative therapies (such as thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy;
* Was receiving systemic glucocorticoid therapy (excluding nasal, inhalation, or other routes of topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to initial administration; Note: Physiological doses of glucocorticoids (≤10 mg/ day of prednisone or equivalent) are permitted;
* Clinically uncontrollable pleural effusion/abdominal effusion (patients with no need to drain effusion or no significant increase of effusion after 3 days of stopping drainage could be included in the group);
* Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
* Those who are known to be allergic to the active ingredients or excipients of the drug in this study, Pabolizumab, carboplatin and albumin-binding paclitaxel;
* Has not fully recovered from toxicity and/or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or baseline, excluding weakness or hair loss);
* Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive);
* Untreated active hepatitis B (defined as HBsAg positive coupled with a detected HBV-DNA copy number greater than the upper limit of normal in the laboratory of the study center); Note: Hepatitis B subjects who meet the following criteria can also be enrolled:1) HBV viral load \&lt before initial administration; At 1000 copies /ml (200 IU/ml), subjects should receive anti-HBV therapy to avoid viral reactivation throughout the study treatment period.2) For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring of viral reactivation is required
* Active HCV infected subjects (HCV antibody positive and HCV-RNA level above the lower limit of detection);
* Received live vaccine within 30 days prior to initial administration (cycle 1, day 1); Note: Inactivated injectable virus vaccine against seasonal influenza is permitted for 30 days prior to initial administration; But live attenuated influenza vaccines administered intranasally are not allowed.
* Pregnant or lactating women;
* There is any serious or uncontrolled systemic disease, such as:

  1. The resting electrocardiogram (ECG) presents significant and severely uncontrollable abnormalities in rhythm, conduction or morphology, such as complete left bundle branch block, Ⅱ degree or above heart block, ventricular arrhythmia or atrial fibrillation;
  2. Unstable angina pectoris, congestive heart failure, and NYHA grade ≥ 2 chronic heart failure;
  3. Any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, occurred within 6 months before treatment;
  4. Poor blood pressure control (systolic \> 140 mmHg, diastolic \> 90 mmHg);
  5. A history of non-infectious pneumonia requiring glucocorticoid therapy or clinically active interstitial lung disease within 1 year prior to initial administration;
  6. Active pulmonary tuberculosis;
  7. There is an active or uncontrolled infection that requires systemic treatment;
  8. Clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction;
  9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
  10. Poor diabetes control (fasting blood glucose (FBG) \> 10mmol/L);
  11. Urine routine indicated urine protein ≥++, and confirmed 24 hours urine protein quantity \> 1.0 g;
  12. Patients with mental disorders and unable to cooperate with treatment;
* Medical history or evidence of disease that may interfere with test results, prevent participants from participating fully in the study, abnormal values of treatment or laboratory tests, or other conditions that the investigator considers unsuitable for enrollment. The Investigator considers other potential risks unsuitable for participation in the study.

Where this trial is running

Guangzhou, Guangdong

• Sun yat-sen memorial hospital — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Jinsong Li, MD

Conditions HNSCC; Oral Cancer; PD-1