Iparomlimab and Tuvonralimab Plus Hypofractionated Radiotherapy and Chemotherapy for HAHNSCC

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Radiotherapy; Anti-PD-1/CTLA-4 Antibody
• Intervention / Treatment: Drug: Iparomlimab and Tuvonralimab injection; Radiation: Hypofractionated Radiotherapy; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haiyan Chen, Doctor; Phone Number: 86-86992821; Email: chenhaiyan@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Haiyan Chen, Doctor; Phone Number: 86-86992821; Email: chenhaiyan@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed a written informed consent form and understands and agrees to comply with the study requirements and visit schedule.
2. Male or female subjects aged ≥18 and ≤75 years at the time of signing informed consent.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
4. Histologically or cytologically confirmed stage III-IVB head and neck squamous cell carcinoma as assessed by the investigator.
5. 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).
6. At least one measurable target lesion per RECIST v1.1 criteria.
7. Estimated life expectancy ≥12 weeks.

8. 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):

   1. Hematology: ANC ≥1.5 × 10⁹/L or within normal range; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L.
   2. 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.
   3. 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).
   4. Coagulation: International normalized ratio (INR) ≤1.5; activated partial thromboplastin time (APTT) ≤1.5 × ULN.
9. 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).

Exclusion Criteria:

1. History of allergy to any component of anti-PD-1/CTLA-4 antibodies or cisplatin.
2. 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).

3. Uncontrolled cardiac symptoms or diseases, including:

   1. New York Heart Association (NYHA) class II or higher heart failure.
   2. Unstable angina.
   3. Myocardial infarction within the past year.
   4. Clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.

4. Prior treatments, including:

   1. Previous treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies.
   2. Use of any investigational drug within 4 weeks prior to the first dose of study drug.
   3. Concurrent participation in another clinical trial, unless it is an observational (non-interventional) study.
   4. 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.
   5. Receipt of an antitumor vaccine or live vaccine within 4 weeks before the first dose of study drug.
   6. Major surgery or severe trauma within 4 weeks before the first dose of study drug.
5. Failure to recover from previous antitumor therapy to ≤Grade 1 per CTCAE criteria (except for alopecia and residual neuropathy related to prior platinum therapy), or laboratory results not meeting the inclusion/exclusion thresholds.
6. 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.
7. Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). However, patients with autoimmune hypothyroidism on stable replacement therapy, type I diabetes on stable insulin therapy, vitiligo, or childhood asthma/allergies resolved in adulthood without intervention are eligible.
8. History of immunodeficiency, including HIV positivity, acquired or congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation.
9. History of interstitial lung disease (excluding radiation pneumonitis not requiring steroids) or noninfectious pneumonitis.
10. Active tuberculosis based on history or CT imaging; active TB within 1 year prior to enrollment; or remote history of TB (>1 year prior) without appropriate treatment.
11. Active hepatitis B (HBV DNA ≥500 IU/mL or ≥2500 copies/mL) or active hepatitis C (anti-HCV positive with HCV RNA above lower limit of detection).
12. History of substance abuse, alcohol abuse, or drug dependence.
13. Pregnant or breastfeeding women.
14. Subjects whom the investigator considers unsuitable due to factors that may lead to early study discontinuation, such as severe comorbidities requiring concurrent treatment (including psychiatric disorders), significantly abnormal laboratory values, or family/social conditions that may affect subject safety or data collection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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; 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.; Radiation: Hypofractionated Radiotherapy; hypofractionated radiotherapy (5 Gy × 3) for two cycles; Drug: Chemotherapy; sequential concurrent chemoradiotherapy (50 Gy/25 fractions with two cycles of cisplatin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events.	The incidence, type, and severity of adverse events (AEs), serious AEs, and immune-related AEs (irAEs) were assessed in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0).	From enrollment to the end of treatment at 3 years.
Objective Response Rate (ORR)	Objective Response Rate (ORR) refers to the proportion of patients who achieve a measurable reduction in tumor burden, specifically those who experience a complete response (CR) or partial response (PR) according to standardized criteria (such as RECIST).	From enrollment to the first documented tumor response assessment
Progression-free survival(PFS)	Progression-free survival is the length of time from the start of treatment (or from randomization/enrollment) until the disease progresses or the patient dies from any cause, whichever occurs first.	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)	Distant Metastasis-Free Survival (DMFS) is the length of time from the start of treatment (or from diagnosis/enrollment) until the first occurrence of distant metastasis or death from any cause, whichever happens first.	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)	Overall Survival(OS) is defined as the period from the date of first treatment administration to the date of death due to any cause.	From the date of enrollment until the date of death due to any cause.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: hypofractionated radiotherapy; Head and neck squamous cell carcinoma; anti-PD-1/CTLA-4 antibody
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Therapeutics; Radiotherapy; Dose Fractionation, Radiation; Radiotherapy Dosage; Drug Therapy; Radiation Dose Hypofractionation
• Other Study ID Numbers: 2025-0946

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No