Neoadjuvant Chemotherapy Combined With Bispecific Antibody Versus Monoclonal Antibody in Locally Advanced NSCLC

NCT ID: NCT06837948

Last Updated: 2025-02-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-18
• Study Completion Date: 2031-12-01

Brief Summary

Surgical intervention remains the primary treatment option for early-stage lung cancer. With the proven efficacy of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC), neoadjuvant immunotherapy has increasingly become a focal point of research. Blocking vascular endothelial growth factor (VEGF) not only inhibits the proliferation of vascular endothelial cells and the formation of new blood vessels but also improves the tumor microenvironment and enhances the infiltration of cytotoxic T lymphocytes within it. Simultaneously targeting the VEGF and PD-L1 pathways can create a synergistic anti-cancer effect. PM8002 injection is a bispecific antibody drug that targets both PD-L1 and VEGF, functioning as a dual-action agent that combines immune suppression and anti-angiogenesis. In patients with locally advanced stage II-III NSCLC, neoadjuvant therapy that concurrently targets PD-L1/VEGF in combination with chemotherapy can improve pathological response rates, provided that the safety of the drug combination is maintained. This approach offers additional benefits to patients, prolongs event-free survival (EFS), and improves prognosis.

Conditions

Locally Advanced Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Exploratory arm

In this arm, 20 patients with locally advanced Non-small cell lung cancer will receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.

Group Type: EXPERIMENTAL

PM8002

Intervention Type: DRUG

Specified dose on specified days.

Nab-paclitaxel

Intervention Type: DRUG

Specified dose on specified days.

Carboplatin

Intervention Type: DRUG

Specified dose on specified days.

Surgery

Intervention Type: PROCEDURE

Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.

PM8002 arm

Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant PM8002 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.

Group Type: EXPERIMENTAL

PM8002

Intervention Type: DRUG

Specified dose on specified days.

Nab-paclitaxel

Intervention Type: DRUG

Specified dose on specified days.

Carboplatin

Intervention Type: DRUG

Specified dose on specified days.

Surgery

Intervention Type: PROCEDURE

Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.

Sintilimab arm

Patients with locally advanced Non-small cell lung cancer will be randomized into this arm (70 patients) and receive 4 circles of neoadjuvant Sintilimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.

Group Type: ACTIVE_COMPARATOR

Sintilimab

Intervention Type: DRUG

Specified dose on specified days.

Nab-paclitaxel

Intervention Type: DRUG

Specified dose on specified days.

Carboplatin

Intervention Type: DRUG

Specified dose on specified days.

Surgery

Intervention Type: PROCEDURE

Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.

Interventions

PM8002

Specified dose on specified days.

Intervention Type: DRUG

Sintilimab

Specified dose on specified days.

Intervention Type: DRUG

Nab-paclitaxel

Specified dose on specified days.

Intervention Type: DRUG

Carboplatin

Specified dose on specified days.

Intervention Type: DRUG

Surgery

Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. The patient shall sign the Informed Consent Form.

2. Aged 18 ≥ years.

3. Histological or cytological diagnosis of NSCLC by needle biopsy, and stage II-III confirmed by imageological examinations (CT, PET-CT or EBUS)，and have not previously received anti-tumor treatment.

4. Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1.

5. Life expectancy is at least 12 weeks.

6. At least 1 measurable lesion according to RECIST 1.1.

7. Patients with good function of other main organs (liver, kidney, blood system, etc.)

8. Patients with lung function can tolerate surgery;

9. Without systematic metastasis (including M1a, M1b and M1c);

10. Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative.

11. Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later).

Exclusion Criteria

1. Patients with lung adenocarcinoma with confirmed EGFR mutations or ALK rearrangements;

2. Histological evidence of small cell components;

3. Patients with other malignant tumors within five years prior to the start of this trial;

4. Having received any systemic anti-cancer treatment for NSCLC, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment, and experimental treatment, etc.;

5. Concomitant unstable systemic diseases, including active infections, uncontrolled hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg), unstable angina, angina that started within the last 3 months, congestive heart failure (≥New York Heart Association [NYHA] Class II), myocardial infarction (within 6 months prior to enrollment), severe arrhythmias requiring drug treatment, liver, kidney, or metabolic diseases;

6. Active, known, or suspected autoimmune diseases, or autoimmune paraneoplastic syndromes requiring systemic treatment;

7. Allergy to the trial drug;

8. Currently diagnosed with interstitial lung disease;

9. Concomitant HIV infection or active hepatitis;

10. Pregnant or lactating women;

11. Patients with neurological or psychiatric disorders who are unable to cooperate;

12. Concurrently participating in another therapeutic clinical study;

13. Other situations deemed unsuitable for enrollment by the investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Pulmonary Hospital, Shanghai, China

OTHER

Sponsor Role: lead

Responsible Party

Peng Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peng Zhang, PhD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Pulmonary Hospital, Shanghai, China

Locations

Shanghai Pulmonary Hospital

Shanghai, , China

Countries

China

Central Contacts

Peng Zhang, PhD

Role: CONTACT

zhangpeng1121@tongji.edu.cn

02165115006

Facility Contacts

Peng Zhang, PhD

Role: primary

zhangpeng1121@tongji.edu.cn

Other Identifiers

LungMate-026

Identifier Type: -

Identifier Source: org_study_id