Iparomlimab and Tuvonralimab Plus Hypofractionated Radiotherapy and Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma: a Multicenter, Single-arm, Phase II Clinical Study
Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at a locally advanced stage, where cisplatin-based chemoradiotherapy is standard but still results in high recurrence rates. Immunotherapy is promising for HNSCC due to its high mutational burden, and adding PD-1 inhibitors to induction chemotherapy has improved responses without added toxicity. Radiotherapy can further stimulate antitumor immunity. Iparomlimab and Tuvonralimab, a dual anti-PD-1/CTLA-4 antibody, has shown strong activity across several solid tumors, and early studies suggest synergy with hypofractionated radiotherapy. However, evidence in locally advanced HNSCC is lacking. The investigators therefore propose a multicenter, single-arm phase II trial to assess the efficacy and safety of combining Iparomlimab and Tuvonralimab injection with chemoradiotherapy in locoregionally advanced HNSCC.
• Signed a written informed consent form and understands and agrees to comply with the study requirements and visit schedule.
• Male or female subjects aged ≥18 and ≤75 years at the time of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
• Histologically or cytologically confirmed stage III-IVB head and neck squamous cell carcinoma as assessed by the investigator.
• No prior systemic therapy for head and neck squamous cell carcinoma (including chemotherapy, EGFR monoclonal antibodies, anti-PD-1 or anti-PD-L1 antibodies, anti-CTLA-4 antibodies, or other immune checkpoint inhibitors).
• At least one measurable target lesion per RECIST v1.1 criteria.
• Estimated life expectancy ≥12 weeks.
• Adequate bone marrow and organ function (without receiving any cellular products, blood components, colony-stimulating factors, or cytokine therapy within 14 days prior to laboratory testing):
‣ Hematology: ANC ≥1.5 × 10⁹/L or within normal range; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L.
⁃ Liver function: Total bilirubin ≤1.5 × ULN; for Gilbert's syndrome, TBIL ≤3 × ULN; AST and ALT ≤2.5 × ULN in patients without liver metastasis, or ≤5 × ULN in those with liver metastasis; albumin ≥28 g/L.
⁃ Renal function: Serum creatinine ≤1.5 × ULN, or creatinine clearance (CCR) ≥60 mL/min (calculated via Cockcroft-Gault formula or measured via 24-hour urine collection); urine dipstick protein \<2+. For subjects with baseline ≥2+ proteinuria, a 24-hour urine test must show \<1 g of protein (if both tests are done, the 24-hour result will determine eligibility).
⁃ Coagulation: International normalized ratio (INR) ≤1.5; activated partial thromboplastin time (APTT) ≤1.5 × ULN.
• Subjects who are infertile or agree to use at least one highly effective contraceptive method during the study (starting 14 days before screening or first dose, whichever occurs earlier, and continuing until 180 days after the last dose of study drug).