Iparomlimab and Tuvonralimab Plus Hypofractionated Radiotherapy and Chemotherapy for HAHNSCC

NCT07447570 | Recruiting Phase 2

• 1 other identifier: 2025-0946
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Head and Neck Cancer; Radiotherapy; Anti-PD-1/CTLA-4 Antibody

Keywords

Head and neck squamous cell carcinoma; hypofractionated radiotherapy; anti-PD-1/CTLA-4 antibody

Outcome Measures

Primary Outcomes (1)

• 1-year progression-free survival rate (1-year PFS rate)

  The proportion of patients who remain alive without disease progression (including local recurrence, regional recurrence, distant metastasis, or death) one year after the start of treatment.

  1 year from the date of enrollment

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  From enrollment to the first documented tumor response assessment

• Progression-free survival(PFS)

  From the date of enrollment until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 1 year.

• Distant Metastasis-Free Survival (DMFS)

  From the date of enrollment until the date of first documented distant metastasis or death from any cause, whichever occurs first, assessed up to 1 year.

• Overall Survival(OS)

  From the date of enrollment until the date of death due to any cause.

• Adverse events.

  From enrollment to the end of treatment at 3 years.

Study Arms (1)

Experimental

EXPERIMENTAL

Induction therapy include Iparomlimab and Tuvonralimab injection combined with hypofractionated radiotherapy (5 Gy × 3) for two cycles, followed by sequential concurrent chemoradiotherapy (50 Gy/25 fractions with two cycles of cisplatin). After completing chemoradiotherapy, patients receive maintenance Iparomlimab and Tuvonralimab injection for at least six months.

Drug: Iparomlimab and Tuvonralimab injection; Radiation: Hypofractionated Radiotherapy; Drug: Chemotherapy

Interventions

Iparomlimab and Tuvonralimab injection DRUG

Induction therapy include Iparomlimab and Tuvonralimab injection combined with hypofractionated radiotherapy (5 Gy × 3) for two cycles, followed by sequential concurrent chemoradiotherapy (50 Gy/25 fractions with two cycles of cisplatin). After completing chemoradiotherapy, patients receive maintenance Iparomlimab and Tuvonralimab injection for at least six months.

Experimental

Hypofractionated Radiotherapy RADIATION

hypofractionated radiotherapy (5 Gy × 3) for two cycles

Experimental

Chemotherapy DRUG

sequential concurrent chemoradiotherapy (50 Gy/25 fractions with two cycles of cisplatin)

Experimental

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• History of allergy to any component of anti-PD-1/CTLA-4 antibodies or cisplatin.
• History or presence of another malignancy (except those cured and without recurrence for more than 5 years, including basal cell carcinoma, carcinoma in situ of the cervix, and papillary thyroid carcinoma).
• Uncontrolled cardiac symptoms or diseases, including:
• New York Heart Association (NYHA) class II or higher heart failure.
• Unstable angina.
• Myocardial infarction within the past year.
• Clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.
• Prior treatments, including:
• Previous treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies.
• Use of any investigational drug within 4 weeks prior to the first dose of study drug.
• Concurrent participation in another clinical trial, unless it is an observational (non-interventional) study.
• Requirement for systemic corticosteroid therapy (≥10 mg prednisone or equivalent/day) or other immunosuppressive drugs within 2 weeks prior to the first dose of study drug, except for topical or inhaled steroids, or prophylaxis for nausea, vomiting, or allergic reactions. Other special circumstances should be discussed with the investigator. In the absence of active autoimmune disease, inhaled or topical corticosteroids and physiologic replacement doses of adrenal corticosteroids equivalent to \>10 mg/day prednisone are allowed.
• Receipt of an antitumor vaccine or live vaccine within 4 weeks before the first dose of study drug.
• Major surgery or severe trauma within 4 weeks before the first dose of study drug.
• Severe infection (CTCAE \> Grade 2) within 4 weeks before the first dose of study drug, including severe pneumonia, bacteremia, infections requiring hospitalization, evidence of active pulmonary inflammation on baseline imaging, symptoms or signs of infection within 4 weeks prior to first dose, or requiring oral or IV antibiotics.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital Of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Radiation Dose Hypofractionation; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Central Study Contacts

Haiyan Chen, Doctor

CONTACT

86-86992821; chenhaiyan@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2025
• First Posted: March 3, 2026
• Study Start: October 15, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 3, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)