Phase II Multi-centered Study of Perioperative Ivonescimab Versus Pembrolizumab Combined with Standard of Care (SOC) in Patients with Resectable, Locally Advanced Head and Neck Squamous Cell Carcinoma

Sponsor
Fudan University
Study ID
NCT06814067
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pembrolizumab — DRUG
    Two cycles of neoadjuvant pembrolizumab (200mg q3w) followed by radical surgery. Adjuvant radiotherapy/chemoradiotherapy is decided based on pathological risk factors. Fifteen cycles of pembrolizumab (200mg q3w)maintenance therapy was given.
  • Ivonescimab — DRUG
    Two cycles of neoadjuvant Ivonescimab (10mg/kg q3w) followed by radical surgery. Adjuvant radiotherapy/chemoradiotherapy is decided based on pathological risk factors. Fifteen cycles of Ivonescimab maintenance therapy (10mg/kg q3w) was given.
  • Surgery — PROCEDURE
    Radical surgery
  • Adjuvant radiotherapy — RADIATION
    Adjuvant radiotherapy with/without concurrent cisplatin-based chemotherapy, based on pathologic risk factors.

Study Details

Head and neck squamous cell carcinoma (HNSCC) is one of the common malignant tumors in the world. More than 60% of HNSCC patients are locally advanced when first diagnosed. The treatment effect of locally advanced HNSCC is not ideal. About 50-60% of patients will have local recurrence within 2 years, and 20-30% of patients will have distant metastasis. The 5-year disease control rate is approximately 40%, and the 5-year overall survival rate is less than 50%. In recent years, PD-1 inhibitors have shown significant efficacy in recurrent/metastatic HNSCC. The Keynote 040 and Checkmate 141 studies established the status of PD-1 inhibitors as second-line treatment in recurrent/metastatic HNSCC. The Keynote 048 study further established the value of PD-1 inhibitors alone or in combination with chemotherapy in the first-line treatment of recurrent/metastatic HNSCC. An increasing number of studies have attempted to explore the value of neoadjuvant therapy with PD-1 inhibitors in locally advanced HNSCC. For example,The Checkmate 358 study showed that the clinical objective response rate of neoadjuvant nivolumab monotherapy was 10.2%, and the major pathological response rate (MPR) was 2.9%. Ivonescimab is a new PD-1/VEGF bispecific antibody drug, which can block both the PD-1 pathway and the VEGF pathway. This dual blocking mechanism is expected to enhance the efficacy of immunotherapy by improving the tumor microenvironment. Ivonescimab has been studied in Phase II to Phase III clinical studies in multiple tumor types such as lung cancer, breast cancer, and head and neck squamous cell carcinoma. For example, the HARMONi-2 study showed that ivocilizumab monotherapy had significantly better progression-free survival (PFS) than pembrolizumab in the treatment of PD-L1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). In recurrent and metastatic HNSCC, Ivonescimab alone or in combination with the CD47 monoclonal antibody Ligufalimab has better objective response rate (ORR) and disease control rate (DCR) than pembrolizumab. The aim of this study is to compare the efficacy and safety of perioperative treatment with Ivonescimab and pembrolizumab in surgically resectable locally advanced head and neck squamous cell carcinoma.

Key Dates

Start date
Feb 10, 2025
Status verified
Feb 2025
Primary completion
Feb 10, 2029
Completion
Mar 1, 2030

Study Design

Enrollment
80 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Perioperative pembrolizumab
    Neoadjuvant pembrolizumab two cycles, followed by radical surgery. Adjuvant radiation/chemoradiation was decided based on pathologic risk factors. Then maintenance therapy of pembrolizumab for fifteen cycles was given.
  • Experimental: Perioperative Ivonescimab
    Neoadjuvant ivonescimab two cycles, followed by radical surgery. Adjuvant radiation/chemoradiation was decided based on pathologic risk factors. Then maintenance therapy of ivonescimab for fifteen cycles was given.

Primary Outcome Measure

Major pathological response [ Time Frame: 4 months ]

Central Contacts

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