This is a single-arm, open-label, phase II study to evaluate the efficacy and safety of the combination of the antibodies iparomlimab and tuvonralimab, administered with or without chemotherapy, in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) who have progressed after receiving at least one line of systemic therapy.
The study includes a safety run-in phase with approximately three patients, which may be expanded to six if a dose-limiting toxicity is observed. Patients are then assigned to either combination antibody monotherapy or combination antibody plus chemotherapy, based on PD-L1 combined positive score (CPS), symptom burden, disease characteristics and patient preference.
Monotherapy involves iparomlimab and tuvonralimab (5 mg/kg on day 1, every 3 weeks).
Combination therapy involves the same antibody regimen plus up to six cycles of platinum (carboplatin at an area under the curve (AUC) of 5 or cisplatin at 75 mg/m²) plus docetaxel (75 mg/m²) or paclitaxel (135-175 mg/m²), followed by antibody monotherapy maintenance.
The primary objective is to assess the objective response rate (ORR) according to RECIST 1.1. The secondary objectives are to evaluate the disease control rate (DCR), the 6-month progression-free survival (PFS) rate, the 6-month overall survival (OS) rate and the safety profile. Exploratory objectives include the association of tumour biomarkers (PD-L1 expression and tumour mutation burden) with efficacy.
Sign a written informed consent form before any trial-related procedures are performed；
Ages 18 to 75, regardless of gender；
ECOG performance status of 0-2；
Pathologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck, including the oropharynx, oral cavity, hypopharynx, or larynx；
Total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within the normal range. (These levels may be controlled by thyroid replacement therapy.) Asymptomatic subjects with abnormal T3, free T3, or free T4 levels may be enrolled；
Patients must have adequate organ and bone marrow function, and laboratory test results within 7 days prior to grouping must meet the following requirements (conditions must not be met by administering any blood components, cell growth factors, albumin, or other corrective medications within 14 days prior to obtaining the laboratory tests), as follows: 1) Complete blood count (CBC): Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count (PLT) ≥ 75 × 10⁹/L (≥ 50 × 10⁹/L for patients with cirrhosis or splenomegaly); Hemoglobin (HGB) ≥ 90 g/L; 2) Liver function: Serum total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5×ULN; 3) Renal function: Serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (CCr) ≥ 50 mL/min (Cockcroft-Gault formula); Qualitative urine protein ≤ 1+; if qualitative urine protein is ≥ 2+, a 24-hour urine protein quantification test must be performed; if the 24-hour urine protein quantification is < 1 g, it is acceptable; Coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 2 times the upper limit of normal (ULN).
Single group
Iparomlimab and tuvonralimab
DrugPatients are assigned to either combination antibody monotherapy or combination antibody plus chemotherapy based on PD-L1 CPS, symptom burden, disease characteristics, and patient preference. Monotherapy arm: Iparomlimab and tuvonralimab combination antibody 5 mg/kg intravenously on day 1 of each 21-day cycle, repeated until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria. Combination arm: The same antibody regimen (5 mg/kg on day 1, every 3 weeks) plus chemotherapy for up to 6 cycles. Chemotherapy consists of: Platinum (carboplatin AUC 5 or cisplatin 75 mg/m²) on day 1, and Either docetaxel 75 mg/m² or paclitaxel 135-175 mg/m² on day 1. After completion of 6 chemotherapy cycles, patients continue on antibody monotherapy alone (same dose and schedule) as maintenance until disease progression or other discontinuation criteria.
ORR
The proportion of subjects achieving complete remission (CR) and partial remission (PR) out of the total number of subjects
Disease control rate（DCR)
The proportion of patients who achieved a response (partial response \[PR\] or complete response \[CR\]) or stable disease (SD) following treatment and were able to maintain this status for at least the minimum duration required, as defined by established response evaluation criteria (such as RECIST 1.1 for solid tumors).
6-month progression-free survival rate
The proportion of subjects who remained free of radiologically confirmed disease progression or death (whichever occurs first) from enrollment through 6 months
6-month overall survival rate
The proportion of participants who were still alive at the end of the 6-month study period
Incidence of adverse events
Incidence, severity, and relationship to the study drug for all adverse events (AE), treatment-emergent adverse events (TEAE), serious adverse events (SAE), and immune-related adverse events (irAE)
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