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

Peking University Cancer Hospital & Institute

Status and phase: Not yet enrolling; Phase 2

Conditions: Perioperative; II-IIIB (T3N2) Resectable Non-small Cell Lung Cancer

Treatments: Combination Product: Ivonescimab/chemotherapy/surgery; Combination Product: Ivonescimab/surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT07241819

2025YJZ75-ZY01

Details and patient eligibility

About

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.

Enrollment: 66 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Voluntarily sign a written informed consent form;
2. Aged ≥ 18 years and ≤ 75 years , both males and females are eligible;
3. ECOG PS score of 0 or 1;
4. 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);
5. No prior anti-tumor treatment has been received;
6. No known EGFR sensitive mutations/ALK gene translocations;

Exclusion criteria

1. Patients with large cell carcinoma, mixed-cell lung cancer, or those with small cell lung cancer components in the mixture;
2. Presence of locally advanced unresectable or metastatic disease;
3. 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.
4. 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);
5. 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);
6. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 4 patient groups

Arm1 PD-L1 TPS≥50%

Experimental group

Treatment:

Combination Product: Ivonescimab/surgery

Arm2 PD-L1 TPS≥50%

Active Comparator group

Treatment:

Combination Product: Ivonescimab/chemotherapy/surgery

Combination Product: Ivonescimab/chemotherapy/surgery

Combination Product: Ivonescimab/chemotherapy/surgery

Arm3 PD-L1 TPS<50%

Experimental group

Treatment:

Combination Product: Ivonescimab/chemotherapy/surgery

Combination Product: Ivonescimab/chemotherapy/surgery

Combination Product: Ivonescimab/chemotherapy/surgery

Arm4 PD-L1 TPS<50%

Active Comparator group

Treatment:

Combination Product: Ivonescimab/chemotherapy/surgery

Combination Product: Ivonescimab/chemotherapy/surgery

Combination Product: Ivonescimab/chemotherapy/surgery