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

NCT07241819 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2025YJZ75-ZY01
• Study Type: interventional
• Target: 66
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Major Pathological response，MPR

  At the time of postoperative pathological assessment，Up to approximately 2 years

• R0 resection rate

  At the time of postoperative pathological assessment，Up to approximately 2 years

• Objective Response Rate，ORR

  After completion of neoadjuvant therapy and before surgery，Up to approximately 2 years

• 24 months Event-Free Survival（EFS）%

  At 24 months after the first administration of study drug to the subjects

• incidence rate of adverse events

  Up to approximately 2 years

Other Outcomes (2)

• 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

Study Arms (4)

Arm1 PD-L1 TPS≥50%

EXPERIMENTAL

Combination Product: Ivonescimab/surgery

Arm2 PD-L1 TPS≥50%

ACTIVE COMPARATOR

Combination Product: Ivonescimab/chemotherapy/surgery

Arm3 PD-L1 TPS<50%

EXPERIMENTAL

Combination Product: Ivonescimab/chemotherapy/surgery

Arm4 PD-L1 TPS<50%

ACTIVE COMPARATOR

Combination Product: Ivonescimab/chemotherapy/surgery

Interventions

Ivonescimab/surgery COMBINATION_PRODUCT

Ivonescimab monotherapy (4 cycles)→surgery→Ivonescimab(13 cycles)

Arm1 PD-L1 TPS≥50%

Ivonescimab/chemotherapy/surgery COMBINATION_PRODUCT

Ivonescimab + 1cycle of platinum-based chemotherapy followed by 3 cycles of Ivonescimab monotherapy→surgery→Ivonescimab(13 cycles)

Arm3 PD-L1 TPS<50%

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

MeSH Terms

Interventions

Surgical Procedures, Operative

Central Study Contacts

Nan Wu

CONTACT

+86139 1015 4426; nanwu@bjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 20, 2025
• First Posted: November 21, 2025
• Study Start: November 30, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2028
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share