Ivonescimab Monotherapy or in Combination With Chemotherapy as Neoadjuvant/Adjuvant Therapy for Resectable Non-small Cell Lung Cancer

Official title

Evaluate the Efficacy and Safety of Ivonescimab Monotherapy or in Combination With Chemotherapy as Neoadjuvant/Adjuvant Therapy for Resectable Non-small Cell Lung Cancer

Overview

This study is a prospective, II Phase clinical trial designed to evaluate the efficacy and safety of ivonescimab as monotherapy or in combination with platinum-based chemotherapy in the perioperative treatment of resectable non-small cell lung cancer (NSCLC). Patients are stratified by PD-L1 expression level (TPS ≥50% vs. \<50%) and randomized in a 2:1 ratio to differentiated neoadjuvant treatment arms: PD-L1≥50% subgroup: Ivonescimab monotherapy (4 cycles) vs. ivonescimab + platinum-based chemotherapy (4 cycles); PD-L1\<50% subgroup: Ivonescimab + 1 cycle of chemotherapy followed by 3 cycles of monotherapy vs. ivonescimab + platinum-based chemotherapy (4 cycles). All patients subsequently receive 13 cycles of ivonescimab as adjuvant maintenance therapy postoperatively. As the first study to explore a PD-L1-directed chemotherapy de-escalation strategy, this trial aims to reduce treatment toxicity while maintaining efficacy, thereby providing a novel personalized precision therapy pathway for resectable NSCLC.

Interventions

• Combination product Ivonescimab/surgery
  Ivonescimab monotherapy (4 cycles)→surgery→Ivonescimab(13 cycles)
• Combination product Ivonescimab/chemotherapy/surgery
  Ivonescimab + 1cycle of platinum-based chemotherapy followed by 3 cycles of Ivonescimab monotherapy→surgery→Ivonescimab(13 cycles)
• Combination product Ivonescimab/chemotherapy/surgery
  Ivonescimab + platinum-based chemotherapy (4 cycles)→surgery→Ivonescimab(13 cycles)
• Combination product Ivonescimab/chemotherapy/surgery
  Ivonescimab + platinum-based chemotherapy (4 cycles)→surgery→Ivonescimab(13 cycles)

Primary outcome measures

• Pathological Complete Response（pCR）rate [Time frame: At the time of postoperative pathological assessment，Up to approximately 2 years]

Secondary outcome measures (5)

• Major Pathological response，MPR [Time frame: At the time of postoperative pathological assessment，Up to approximately 2 years]
• R0 resection rate [Time frame: At the time of postoperative pathological assessment，Up to approximately 2 years]
• Objective Response Rate，ORR [Time frame: After completion of neoadjuvant therapy and before surgery，Up to approximately 2 years]
• 24 months Event-Free Survival（EFS）% [Time frame: At 24 months after the first administration of study drug to the subjects]
• incidence rate of adverse events [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Voluntarily sign a written informed consent form;
• Aged ≥ 18 years and ≤ 75 years , both males and females are eligible;
• ECOG PS score of 0 or 1;
• Patients with non-small cell lung cancer confirmed by histopathology or cytology, and with resectable clinical stage II-IIIB (T3N2) (according to the 8th edition of lung cancer TNM staging by the Union for International Cancer Control and the American Joint Committee on Cancer);
• No prior anti-tumor treatment has been received;
• No known EGFR sensitive mutations/ALK gene translocations;

Exclusion criteria

• Patients with large cell carcinoma, mixed-cell lung cancer, or those with small cell lung cancer components in the mixture;
• Presence of locally advanced unresectable or metastatic disease;
• Palliative local treatment for non-target lesions within 2 weeks before the first administration; receipt of non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 used for the treatment of thrombocytopenia) within 2 weeks before the first administration; receipt of Chinese herbal medicines or proprietary Chinese medicines with anti-tumor indications within 1 week before the first administration.
• Severe infection occurred within 4 weeks before the first administration, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection treated with systemic anti-infective therapy within 2 weeks before the first administration (excluding antiviral therapy for hepatitis B or hepatitis C);
• Major surgical operation or severe trauma occurred within 4 weeks before the first administration, or those with a plan for major surgical operation within 4 weeks after the first administration (determined by the researcher); minor local surgery performed within 3 days before the first administration (excluding peripherally inserted central catheterization and venous access port implantation);
• History of severe bleeding tendency or coagulation dysfunction; presence of clinically significant bleeding symptoms within 1 month before the first administration, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing up or expectorating ≥ 1 teaspoon of fresh blood or small blood clots, or coughing up only blood without sputum; those with blood-tinged sputum are allowed to enroll), nasal bleeding (excluding epistaxis and retrograde epistaxis); receipt of continuous antiplatelet or anticoagulant therapy within 10 days before the first administration.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07241819 · 2025YJZ75-ZY01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗