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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Perioperative; II-IIIB (T3N2) Resectable Non-small Cell Lung Cancer
• Intervention / Treatment: Combination product: Ivonescimab/surgery; Combination product: Ivonescimab/chemotherapy/surgery; Combination product: Ivonescimab/chemotherapy/surgery

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nan Wu; Phone Number: +86139 1015 4426; Email: nanwu@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm1 PD-L1 TPS≥50%	Combination product: Ivonescimab/surgery; Ivonescimab monotherapy (4 cycles)→surgery→Ivonescimab(13 cycles)
Active Comparator: Arm2 PD-L1 TPS≥50%	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)
Experimental: Arm3 PD-L1 TPS<50%	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)
Active Comparator: Arm4 PD-L1 TPS<50%	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response（pCR）rate	pCR is defined as the proportion of subjects who have completed surgery and, after the completion of neoadjuvant therapy, have no residual tumor in the resected primary tumor site and lymph nodes as evaluated by local pathology experts.	At the time of postoperative pathological assessment，Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological response，MPR	MPR is defined as the proportion of patients who have completed surgery and, as evaluated by local pathology experts, have residual viable tumor cells accounting for ≤10% in the resected primary tumor foci and lymph nodes.	At the time of postoperative pathological assessment，Up to approximately 2 years
R0 resection rate	the proportion of patients who have completed surgery and achieved a pathological complete resection of the primary tumor, as evaluated by the researchers and local pathology experts.	At the time of postoperative pathological assessment，Up to approximately 2 years
Objective Response Rate，ORR	the proportion of patients whose tumor volume reduction meets the pre-specified criteria (complete response/partial response, CR/PR) and can be maintained for the minimum required duration in accordance with recognized response evaluation criteria (such as RECIST version 1.1 for solid tumors)	After completion of neoadjuvant therapy and before surgery，Up to approximately 2 years
24 months Event-Free Survival（EFS）%	the time from the first administration of the drug in the Full Analysis Set (FAS) to the occurrence of any of the following events, whichever comes first: disease progression evaluated according to RECIST v1.1, local recurrence, distant metastasis, or death from any cause.	At 24 months after the first administration of study drug to the subjects
incidence rate of adverse events		Up to approximately 2 years

Other Outcome Measures

Outcome Measure	Time Frame
Explore biomarkers in subjects' tumor tissues that predict the efficacy of evosimab	Up to approximately 2 years
Explore biomarkers in subjects' blood that predict the efficacy of evosimab	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): November 30, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: July 20, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Surgical Procedures, Operative
• Other Study ID Numbers: 2025YJZ75-ZY01

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
• product manufactured in and exported from the U.S.: No