PD-L1 expression positive recurrent/metastatic head and neck squamous cell carcinoma
Conditions
Interventions
control group:Placebo+ Pabolizumab
experimental group:AK117 + AK112
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign a written informed consent form. 2. Age at the time of enrollment is between 18 and 75 years old, both male and female. 3. The physical fitness score of the Eastern Cooperative Oncology Group (ECOG) is 0 or 1. 4. Expected survival period = 3 months. 5. The subject is diagnosed with locally untreatable recurrent or metastatic HNSCC (according to the 8th edition staging system of the International Union Against Cancer and the Joint American Committee on Cancer) by histology and/or cytology, with the primary tumor located in the mouth, oropharynx, hypophthalmia, or larynx. Note: For subjects with recurrent HNSCC who cannot be cured by local treatment, evaluation by relevant professional physicians and written record confirmation are required. 6. For subjects with oropharyngeal cancer, HPV status testing results based on tumor tissue samples must be obtained before randomization. 7. Have not received systematic anti-tumor treatment for recurrent or metastatic HNSCC in the past. Note: Subjects who have previously received adjuvant/neoadjuvant chemotherapy for non metastatic diseases or radical radiotherapy combined with chemotherapy or cetuximab/rituximab treatment for locally advanced diseases, and whose disease progression occurs more than 6 months after the end of the last treatment, are eligible to participate in this study. 8.According to RECIST v1.1, there should be at least one measurable lesion, or a measurable lesion with clear imaging progression after local treatment, and the lesion is suitable for repeated and accurate measurement. 9. Prior to randomization, the central laboratory detected PD-L1 expression positive (CPS = 1) based on tumor tissue samples. Subjects must provide tumor tissue samples (archived or freshly obtained, strongly recommended for newly obtained tumor tissue samples) diagnosed with recurrent or metastatic tumors or later, approximately 10 unstained formalin fixed paraffin embedded (FFPE) pathological sections (if the central laboratory determines that the samples are insufficient for testing, additional sections are required). We do not accept cell smears from pleural effusion drainage and centrifugation, or samples from biopsy that are insufficient for biomarker detection, as well as bone lesions without soft tissue components or decalcified bone tumor samples. If it is an archived sample, it is required that it has not received any anti-tumor treatment after the collection time, and the collection site has not received radiotherapy. Note: If the archived sample of the subject does not meet the above requirements and the researcher determines that biopsy is not in the best interest of the subject, the acceptance of the archived sample may be allowed after discussion with the sponsor. 10. Determine good organ function through the following requirements: a. Hematology (no use of any blood components or cell growth factor support therapy within 7 days prior to obtaining satisfactory laboratory test results during the screening period): i. Absolute neutrophil count (ANC) = 1.5 × 109/L (1500/mm3); Ii. Platelet count = 100 × 109/L (100000/mm3); Iii. Hemoglobin = 90 g/L. b. Kidney: i. creatinine clearance rate * (CrCl) calculated value = 50 mL/min* The Cockcroft Gault formula will be used to calculate CrCl CrCl (mL/min)={(140- age) x body weight (kg) x F}/(SCr (mg/dL) x 72), where F for males is 1 and F for females is 0.85; SCr=serum creatinine. Ii. Urinary protein = 1+or 24-hour (h) u
Exclusion criteria
Exclusion criteria: 1. Squamous cell carcinoma with a primary site of nasopharyngeal, nasal, sinus, salivary gland, thyroid or parathyroid gland, skin or unknown primary site; 2. Except for HNSCC, the subjects had other malignant tumors within the 5 years prior to enrollment. Subjects with other tumors that have been cured by local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ, are not excluded. 3. Except for HNSCC, the subjects had other malignant tumors within the 5 years prior to enrollment. Subjects with other tumors that have been cured by local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ, are not excluded. 4. Screening imaging shows that the tumor has invaded important surrounding organs (such as the heart and pericardium, trachea, esophagus, etc.) and large blood vessels (such as the aorta, brachiocephalic artery, subclavian artery, common carotid artery, central pulmonary artery, central pulmonary vein, vena cava, etc.), or there is a risk of developing esophageal tracheal fistula or esophageal pleural fistula; Tumor = 180 degrees surrounds important blood vessels; Tumors<180 degrees surround important blood vessels or have obvious necrosis and cavities, and researchers have determined that entering the study would pose a significant risk of bleeding. 5. Existence of brainstem, meningeal metastasis, spinal cord metastasis or compression, or suffering from leptomeningeal disease; There may be active or untreated brain metastases, or brain metastases = 1.5 cm, or brain radiation therapy may be required within the first treatment cycle after randomization. Note: Brain metastases that have undergone previous treatments (such as surgery, radiation therapy, etc.) must be clinically stable for at least 4 weeks before randomization (imaging examination shows stable lesions, no new neurological symptoms, and no evidence of new or increased brain metastases), and corticosteroids should be discontinued 2 weeks before randomization to allow enrollment; Asymptomatic subjects with brain metastases are required to have no neurological symptoms, no need for corticosteroid treatment, and no edema around the brain metastases. 6. There are clinical symptoms or repeated drainage of pleural effusion, pericardial effusion, or peritoneal effusion. 7. Inclusion in another clinical study at the same time, unless it is an observational, non interventional clinical study or a follow-up period of an interventional study; Received study treatment within the first 4 weeks of randomization. 8. Subjects who have previously received immunotherapy, including immune checkpoint inhibitors (such as anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-TIGIT antibodies, anti-LAG3 antibodies, anti-CD47, anti-SIRP a, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, or any other treatment targeting the tumor immune mechanism. 9. Previously received systemic anti angiogenic drug treatment. 10. Previously received radiation therapy for head and neck tumors, including cervical, subclavian, or supraclavicular lymph nodes. 11. Receive radiotherapy for the head and neck within the first 8 weeks of randomization; Palliative local treatment was performed for non head and neck areas within the first 3 weeks of randomization; Received non-specific immunomodulatory ther
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| OS; | — |
Secondary
| Measure | Time frame |
|---|---|
| ORR;DCR;DoR;TTR;PFS;safety and tolerability;Pharmacokinetic (PK) characteristics;immunogenicity; | — |
Countries
China
Contacts
Public ContactKunyu Yang
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed