A Clinical Trial of TQB2618 Injection Combined With Penpulimab Injection and Chemotherapy Versus Penpulimab Injection Combined With Chemotherapy in First-line Treatment of Relapsed/Metastatic Head and Neck Squamous Cell Carcinoma

A Randomized, Open, Multicenter Phase 1/Phase 2 Clinical Trial of TQB2618 Injection Combined With Penpulimab Injection and Chemotherapy Versus Penpulimab Injection Combined With Chemotherapy in First-line Treatment of Relapsed/Metastatic Head and Neck Squamous Cell Carcinoma

To evaluate the efficacy and safety of TQB2618 injection combined with Penpulimab and chemotherapy in the first-line treatment of relapsed/metastatic head and neck squamous cell carcinoma compared to Penpulimab combined chemotherapy.

Progression-free survival (PFS) and objective response rate (ORR) were the primary efficacy endpoints.

Inclusion Criteria:

• The subjects voluntarily joined the study, signed the informed consent form, and had good compliance.

• Between the ages of 18-75 years (calculated based on the date of signing ICF); male or female; Eastern cooperative oncology group (ECOG) score 0-1; estimated survival time ≥ 3 months.

• No indications of local radical therapy for recurrence/metastasis head and neck squamous cell carcinoma.And histologically- or cytologically-confirmed head and neck squamous cell carcinoma ，Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx.

• No systemic therapy for recurrent/metastatic lesions, but excluding systemic therapy for locally advanced disease as a part of multimodal therapy (including induction therapy, systemic therapy in the same period of radiotherapy, and adjuvant therapy), and the completion time of treatment was more than 6 months from enrollment (according to the date of informed consent);

• At least one measurable lesion (based on RECIST1.1).

• The main organs function are normally, the following criteria are met:

  1. hemoglobin (Hb) ≥90g/L (no blood transfusion and blood products within 14 days) ；absolute neutrophil count (ANC) ≥1.5×109/L； platelets (PLT) ≥90×109/L.
  2. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. If accompanied by liver metastases, ALT and AST ≤ 5×ULN; Serum creatinine (CR) ≤ 1.5×ULN or creatinine clearance (CCR) ≥ 60 ml/min.
  3. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5×ULN (no anticoagulant therapy); Thyroid-stimulating hormone (TSH) ≤ ULN; If abnormalities should be examined, T3 and T4 levels should be examined, and T3 and T4 levels are normal.
  4. Cardiac ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%.

• Female participants of childbearing age should agree to use contraception (e.g., IUDs, pills, or condoms) during the study period and for 6 months after the end of the study; Have a negative serum pregnancy test within 7 days prior to study enrollment and must be a non-lactating subject; Male participants should agree that contraception must be used during the study period and for 6 months after the end of the study period.

Exclusion Criteria:

• Comorbidity and medical history:

  1. Have had or currently have other malignant tumors within 3 years. The following two conditions can be enrolled: other malignancies treated with a single surgery to achieve 5-year disease-free survival (DFS); cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumors), Tis (carcinoma in situ) and T1 (tumor-invasive basement membrane)];

  2. adverse effects due to any prior treatment have not been restored to CTCAE 5.0 ≤ level 1 (except for toxicity where the investigator determines that there is no safety risk);

  3. Major surgical treatment, incision biopsy, or significant traumatic injury were received within 28 days prior to study treatment

  4. Long-term unhealed wounds or fractures

  5. Arteriovenous thrombotic events within 6 months, such as cerebrovascular accidents;

  6. Those who have a history of psychotropic substance abuse and cannot quit or have a mental disorder;

  7. Subjects with any severe and/or uncontrolled medical conditions, including:

     1. Unsatisfactory blood pressure control (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥100 mmHg);
     2. Have grade ≥2 myocardial ischemia or myocardial infarction, arrhythmias (including QTc ≥ 450 ms (male) in men and QTc ≥ 470 ms (female)) and grade ≥ congestive heart failure grade 2 (New York Heart Association (NYHA) grade);
     3. Active or uncontrolled severe infection (≥ CTC AE grade 2 infection) or unexplained fever > 38.5°C;
     4. Liver cirrhosis, active hepatitis Note: Active hepatitis (hepatitis B reference: HBsAg positive and HBV (hepatitis B virus) DNA detection value of more than 1000 copies /mL; Hepatitis C reference: HCV (hepatitis C virus) antibody positive, and HCV virus titer test value above the upper limit of normal);
     5. Known to have syphilis;
     6. Renal failure requires hemodialysis or peritoneal dialysis
     7. A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
     8. Poor diabetes control [fasting blood glucose (FBG) > 10mmol/L]
     9. Urine routine indicated urine protein ≥++, and confirmed 24 hours urine protein quantity > 1.0 g
     10. People who have epilepsy and need treatment

• Tumor related symptoms and treatment

  1. Study history of surgery, chemotherapy, radiotherapy, or other anticancer therapy within 4 weeks prior to the start of treatment (washout period from the end of the last treatment)；
  2. progress during or within 6 months of completion of systemic therapy (including induction therapy, concurrent radiotherapy, adjuvant therapy) for locally advanced disease;
  3. Secondary radiotherapy was performed for local recurrent lesions;
  4. Received Chinese patent drugs with anti-tumor indications specified in the Chinese National Medical Product Administration approved drug instructions within 1 week before the study treatment;
  5. Have received relevant immunotherapy drugs in the past;
  6. where imaging (CT or MRI) shows that the tumor has invaded important blood vessels, or the investigator determines that the tumor is highly likely to invade important blood vessels and cause fatal massive bleeding during the follow-up study period;
  7. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (investigator's judgment)
  8. Subjects with known central nervous system metastatic and/or cancerous meningitis;

• Research and treatment related:

  1. Study history of live attenuated vaccine vaccination within 28 days before the start of treatment or planned live attenuated vaccine vaccination during the study period;
  2. Patients with a definite tendency to bleed or clinically significant bleeding symptoms, including but not limited to gastrointestinal bleeding, nasal bleeding, and hemorrhagic disease or coagulopathy within 28 days prior to initial medication;
  3. People who have experienced severe hypersensitivity after the use of monoclonal antibodies, or are allergic to known components of the drug under study;
  4. Study of active autoimmune diseases requiring systemic treatment that occurred within 2 years prior to initiation of treatment;
  5. Have been diagnosed with immunodeficiency or are receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose > 10mg/ day prednisone or other efficacy hormone) and continue to use within 2 weeks before the study therapy begins;

• Participated in clinical trials of other antitumor drugs within 4 weeks before the first medication;

• Subjects who, in the judgment of the investigator, have concomitant diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who are not suitable for inclusion for other reasons.