A Phase I/II Trial of HCB101 in Combination With Pembrolizumab for Patients With Platinum-Refractory, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (SirH&N Trial)
This is a non-randomized, open-label, dose-escalation and dose-expansion phase I/II clinical study to evaluate the safety, tolerability, and efficacy of HCB101 in combination with pembrolizumab in patients with platinum-refractory recurrent/metastatic HNSCC. The trial consists of two phases: the dose-escalation phase (I) and the dose-expansion phase (II). Subjects will receive a weekly single dose of HCB101 IV infusion over 60 (±10) minutes on Days 1, 8, and 15 in each 21-day cycle in combination with pembrolizumab (200 mg IV day 1; given every 21 days) until unacceptable AE(s), radiographic or clinically documented disease progression, withdrawal of consent, loss to follow-up, death, or termination of the study whichever occurs first.
⁃ 1\. Subjects are able to understand and willing to provide signed informed consent as described in protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol, including study visits and study-related procedures.
• 2\. Male and female subjects of ≥18 years of age, inclusive, at the time of signing the informed consent.
• 3\. With histologically/cytologically confirmed diagnosis of HNSCC
• 4\. With progression after 1st cisplatin based therapy for R/M HNSCC or within 6 months after cisplatin based CCRT
• 5\. Must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• 6\. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at Screening.
• 7\. Have a life expectancy of ≥12 weeks (according to the Investigator's judgment).
• 8\. Have adequate organ function, as indicated by the following laboratory parameters in below (had not received a blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor, and other relevant medical support within 14 days prior to the administration of the first dose of study intervention).
∙ a) Absolute neutrophil count ≥1.5 × 109/L
‣ b) Platelets ≥75 × 109/L
‣ c) Hemoglobin ≥9.5 g/dL
‣ d) Total bilirubin ≤1.5 × upper limit of normal (ULN), \<3.0 × ULN if known Gilbert's disease
‣ e) Alanine aminotransferase and aspartate aminotransferase ≤3× ULN and ≤5× ULN for subject with liver metastasis
‣ f) Creatinine clearance ≥50 mL/min (using Cockcroft Gault equation)
‣ g) Coagulation: International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5× ULN (The INR applies only to subjects who do not receive therapeutic anticoagulation). For subjects receiving therapeutic anticoagulation, the INR should be within the therapeutic range for the intended use of the anticoagulants.)
• 9\. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during the Screening Period (within 7 days prior to the first dose of the study intervention).