The Combination of AK104 and Low-dose Radiation Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma After Failure of First-line Systemic Therapy: a Phase II Study
Currently, there is a lack of high-quality clinical evidence for subsequent treatment options for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) after first-line treatment, especially for subsequent treatment after first-line therapy combined with PD-1 inhibitors. Increasing evidence suggests that low-dose radiation (LDRT) can reshape the tumor microenvironment.Cadonilimab is a bispecific antibody that specifically binds to CTLA-4 and PD-1 proteins in the human body. Considering that low-dose radiotherapy and cadonilimab both have immunomodulatory effects, this study intends to select recurrent metastatic HNSCC patients who have failed first-line and above treatment to explore the safety and efficacy of cadonilimab combined with low-dose radiotherapy.
• Patients who signed the informed consent and were willing to complete the study according to the protocol;
• Aged ≥18 years and ≤75 years;
• Histologically confirmed head and neck squamous cell carcinoma or nasopharyngeal carcinoma;
• Patients with recurrent and metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma, with progression on first-line treatment or above; or locally advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma, with recurrence and metastasis within 6 months after radical radiotherapy;
• For patients with locally recurrent head and neck squamous cell carcinoma or nasopharyngeal carcinoma, those who are not suitable for local treatment after multidisciplinary evaluation of head and neck tumors;
• At least one measurable lesion before treatment, that is, meeting the measurable lesion requirement in the RECIST 1.1 standard;
• Expected survival period\>3 months;
• ECOG score 0-2 points;
• Good organ function: meet the following requirements:
∙ Absolute neutrophil count (ANC) ≥1.5×109/L;
‣ Platelet count ≥100×109/L;
‣ Hemoglobin ≥9g/dL;
‣ Serum albumin ≥2.8g/dL;
‣ Total bilirubin ≤1.5×ULN, ALT, AST and/or ALP ≤3×ULN;
‣ Serum creatinine ≤1.5×ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault, see Appendix 3);
‣ Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5× ULN (screening is allowed for patients who are taking stable doses of anticoagulant therapy such as low molecular weight heparin or warfarin and whose INR is within the expected therapeutic range of the anticoagulant);
⁃ Patients with hepatitis B virus (HBV) infection and inactive/asymptomatic HBV carriers, or patients with chronic or active HBV, will be allowed to enroll if HBV DNA \<500 IU/mL (or 2500 copies/mL) at screening. Patients with positive hepatitis C antibodies will be allowed to enroll if HCV-RNA is negative at screening.
⁃ Women of childbearing age need to have a negative urine or serum pregnancy test result within ≤7 days before treatment. And use a medically approved contraceptive method (such as intrauterine device, birth control pills or condoms) during the study treatment, at least 3 months after the last use of cadonilimab, and at least 6 months after the last use of chemotherapy;
⁃ Male subjects who are not sterilized must be willing to use a medically approved contraceptive method (such as intrauterine device, birth control pills or condoms) during the study treatment, at least 3 months after the last use of cadonilimab, and at least 6 months after the last use of chemotherapy.