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

Neoadjuvant Chemotherapy Combined With Bispecific Antibody Versus Monoclonal Antibody in Locally Advanced Non-Small Cell Lung Cancer: A Multicenter, Randomized Controlled Clinical Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Nab-paclitaxel; Drug: Carboplatin; Procedure: Surgery; Drug: PM8002; Drug: Sintilimab

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Zhang, PhD; Phone Number: 02165115006; Email: zhangpeng1121@tongji.edu.cn

Study Locations

• China
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
    • Contact: Peng Zhang, PhD; Email: zhangpeng1121@tongji.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Nab-paclitaxel; Specified dose on specified days.; Drug: Carboplatin; Specified dose on specified days.; Procedure: Surgery; Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.; Drug: PM8002; Specified dose on specified days.
Experimental: 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.	Drug: Nab-paclitaxel; Specified dose on specified days.; Drug: Carboplatin; Specified dose on specified days.; Procedure: Surgery; Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.; Drug: PM8002; Specified dose on specified days.
Active Comparator: 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.	Drug: Nab-paclitaxel; Specified dose on specified days.; Drug: Carboplatin; Specified dose on specified days.; Procedure: Surgery; Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.; Drug: Sintilimab; Specified dose on specified days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response (PCR) rate	PCR rate is defined as the proportion of participants who have achieved pathologic complete response (on routine hematoxylin and eosin staining, no tumor cell can be found in tumor bed or lymph node) in all participants.	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response (MPR) rate	MPR rate is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants.	Up to 30 months
Treatment-related adverse event (TRAE)	TRAE is defined and classified according to NCI-CTCAE v5.0 in all participants.	Up to 30 months
R0 resection rate	R0 resection rate is defined as the proportion of participants who have achieved R0 resection (complete resection with no residual tumor cell in the resection margin) in all participants.	Up to 30 months
Event-free survival (EFS)	Event-free survival (EFS) is defined as the length of time (months) from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	Up to 60 months
Overall survival (OS)	It is defined as the time (months) from enrollment to death of participant due to any cause. In the case of a patient who still survives at the time of analysis, the date of last contact will be taken as the censoring date.	Up to 60 months
Objective response rate (ORR)	ORR is defined according to the RECIST v1.1 criteria.	Up to 30 months
Health related quality of life (HRQol) composite	The assessment is made according to the Quality of Life Scale for Lung Cancer Patients (EORTC-QLQ-C30 & LC13, Version 3). EORTC's QLQ-C30 & LC13 (V3.0) is a core scale for lung cancer patients, with a total of 43 items. Among them, Item 29 and 30 are divided into seven grades, which are assigned with 1 to 7 scores according to the answer options. The other items are divided into 4 grades: Not at All, A Little, Quite a Bit, and Very Much, assigned with 1 to 4 scores respectively. The higher score, the worse quality.	Up to 5 months

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China
• Investigators: Principal Investigator: Peng Zhang, PhD, Shanghai Pulmonary Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Estimated): February 18, 2025
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: LungMate-026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The researchers will consider whether IPD is available to other researchers only after the paper is published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No