Iparomlimab and Tuvonralimab Combined With SFRT and Definitive Chemoradiotherapy in Locoregionally Advanced Bulky HNSCC

NCT07041788 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT-I-2025-013
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Study Objectives

1. 1.Primary Objective:
2. 2.Secondary Objectives:s
3. 3.2-Year Overall Survival (OS) Rate
4. 4.2-Year Distant Metastasis-Free Survival (DMFS) Rate.
5. 5.2-Year Local Region Recurrence-Free Survival (LRRFS) Rate.
6. 6.Objective Response Rate (ORR).
7. 7.Duration of Response (DoR).
8. 8.Quality of Life (QoL):
9. 9.Safety:
10. 10.Tolerability:

Conditions

Cancer

Keywords

Spatially Fractionated Radiation Therapy; Ipalontilimab and Tuvorilimab; Locoregionally advance head and neck squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• 2-year EFS (Event - Free Survival)

  Event-Free Survival (EFS) rate: Defined as the time from enrollment to the occurrence of the first event among any of the following: disease progression (including local progression and distant metastasis), recurrence (i.e., reappearance of the tumor after treatment in cancer patients), death from any cause, etc. In other words, it represents the survival duration during the observation period when patients do not experience these predefined "events".

  2 years

Secondary Outcomes (7)

• 2 - year Overall Survival (OS) rate

  2 years

• 2 - year Distant Metastasis - Free Survival (DMFS) rate

  2 years

• 2 - year Local Region Recurrence - Free Survival (LRRFS) rate

  2 years

• Overall Response Rate (ORR)

  2 years

• Duration of Response (DoR)

  2 years

Study Arms (1)

Study of Iparomlimab and Tuvonralimab Combined With SFRT and Definitive Chemoradiotherapy in HNSCC

EXPERIMENTAL

This is a single-arm study.(1) Induction therapy: Administer Spatially Fractionated Radiotherapy to the tumor at a dose of 10 - 20 Gy in 1 fraction. Subsequently, conduct 3 cycles of induction chemotherapy (docetaxel 75 mg/m² on day 1, cisplatin 25 mg/m² from day 1 to day 3, every 3 weeks for 3 cycles) combined with immunotherapy using Iparomlimab and Tuvonralimab (5 mg/kg on day 1, every 3 weeks for 3 cycles). (2) Concurrent chemoradiotherapy: Initiate radical concurrent chemoradiotherapy within 2 - 4 weeks after the completion of induction therapy. The prescribed dose of radical radiotherapy is 70 Gy for the primary tumor and 66 - 70 Gy for the positive cervical lymph nodes, to be delivered in 30 - 33 fractions. Concurrent chemotherapy involves intravenous. (3) Maintenance therapy: Start maintenance immunotherapy with Iparomlimab and Tuvonralimab 4 - 6 weeks after the completion of concurrent chemoradiotherapy. Administer it at a dose of 5 mg/kg per administration.

Drug: Iparomlimab and Tuvonralimab Injection

Interventions

Iparomlimab and Tuvonralimab Injection DRUG

Induction Therapy: Spatially Fractionated Radiotherapy: Administer 10-20 Gy in a single fraction to the tumor. Chemotherapy + Immunotherapy: Docetaxel 75 mg/m² IV on Day 1. Cisplatin 25 mg/m² IV on Days 1-3. Iparomlimab and Tuvonralimab Injection 5 mg/kg IV on Day 1. Cycles: Every 3 weeks (Q3W) for 3 cycles. Maintenance Therapy: Begin 4-6 weeks after radiotherapy completion. Iparomlimab and Tuvonralimab: Dose: 5 mg/kg diluted in 100 mL 0.9% NaCl or 5% glucose. Administration: IV infusion over ≥20 minutes (total duration including flushing ≤60 minutes). Cycles: Q3W for 14 cycles (maximum 1 year). Iparomlimab and Tuvonralimab Injection: Continue until disease progression, intolerable toxicity, initiation of new anti-tumor therapy, withdrawal of consent, or investigator decision to discontinue. Maximum treatment duration: 1 year.

Study of Iparomlimab and Tuvonralimab Combined With SFRT and Definitive Chemoradiotherapy in HNSCC

Eligibility Criteria

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

You may qualify if:

• Age between 18 and 75 years, both sexes eligible;
• Histologically confirmed head and neck squamous cell carcinoma (HNSCC), diagnosed as locoregionally advanced disease with measurable primary tumor and/or cervical metastatic lymph nodes \>5 cm in maximum diameter, and deemed unresectable by surgical evaluation;
• Treatment-naive (no prior anti-tumor therapy);
• At least one measurable lesion (excluding brain metastases) per RECIST 1.1 criteria;
• ECOG performance status 0-1;
• Life expectancy ≥12 weeks;
• Organ function meeting the following criteria (no blood products, colony-stimulating factors, leukocyte/ thrombocyte/ erythrocyte-stimulating agents within 14 days prior to first study drug administration):
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L;
• Platelets ≥90×10\^9/L;
• Hemoglobin ≥8 g/dL;
• Serum albumin ≥2.8 g/dL;
• Total bilirubin ≤1.5×ULN, ALT/AST/ALP ≤2.5×ULN; if liver metastases present, ALT/AST ≤5×ULN; if liver/bone metastases present, ALP ≤5×ULN;
• Serum creatinine ≤1.5×ULN or creatinine clearance \>60 mL/min;
• APTT and INR ≤1.5×ULN (patients on stable anticoagulation \[e.g., LMWH, warfarin\] with therapeutic INR acceptable for screening).
• Voluntary informed consent, good compliance, and willingness to cooperate with follow-up;

You may not qualify if:

• Those with a history of severe immediate - type allergic reactions to any of the drugs used in this study；
• Within six months before screening, having any of the following conditions: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. Patients known to have coronary artery disease, congestive heart failure that doesn't meet the above criteria, or a left ventricular ejection fraction of less than 50% must have an optimally stable medical regimen as determined by the treating physician. If appropriate, a cardiologist can be consulted；
• Individuals who have received anti - tumor vaccines or live vaccines within four weeks before the first administration of the study drug；
• Patients with active autoimmune diseases or a history of autoimmune diseases that are likely to relapse. The following patients are not excluded and can proceed to further screening:
• Those with well - controlled type 1 diabetes.
• Patients with hypothyroidism that can be controlled with hormone replacement therapy alone.
• People with skin diseases that do not require systemic treatment, such as vitiligo, psoriasis, and alopecia.
• Any other diseases that are not expected to relapse without external triggers；
• Those lacking full or restricted civil capacity；
• Patients with physical or mental disorders who, in the investigator's opinion, are unable to fully or adequately understand the potential complications of this study；
• Patients with an expected survival time of less than three months；
• Patients with significantly reduced functions of the heart, liver, lungs, kidneys, and bone marrow；
• Those with a history of substance abuse or alcohol addiction；
• Patients whose tumor lesions invade large blood vessels, such as the internal carotid artery and jugular vein and their main branches, with a high risk of bleeding；
• Subjects who need systemic treatment with corticosteroids (more than 10 mg/day prednisone equivalent) or other immunosuppressants within two weeks before the first use of the study drug, except for the use of corticosteroids for local esophageal inflammation and the prevention of allergies, nausea, and vomiting. In other special cases, communication with the sponsor is required. In the absence of active autoimmune diseases, the inhalation or local use of steroids and adrenal cortical hormone replacement at a dose higher than 10 mg/day prednisone equivalent is allowed；

Sponsors & Collaborators

• Second Affiliated Hospital of Nanchang University: lead
• Qilu Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Lei Zeng

  Second Affiliated Hospital of Nanchang University

  STUDY CHAIR

Central Study Contacts

Lei Zeng

CONTACT

+8618870846505; ndefy19019@ncu.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: March 26, 2025
• First Posted: June 27, 2025
• Study Start: April 28, 2026
• Primary Completion (Estimated): July 9, 2028
• Study Completion (Estimated): July 9, 2030
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

CN (1)