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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exploratory arm | Experimental | 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. |
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| PM8002 arm | Experimental | 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. |
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| Sintilimab arm | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PM8002 | Drug | Specified dose on specified days. |
| |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Peng Zhang, PhD | Contact | 02165115006 | zhangpeng1121@tongji.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Peng Zhang, PhD | Shanghai Pulmonary Hospital, Shanghai, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Pulmonary Hospital | Shanghai | 200433 | China |
The researchers will consider whether IPD is available to other researchers only after the paper is published.
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| Sintilimab |
| Drug |
Specified dose on specified days. |
|
| Nab-paclitaxel | Drug | Specified dose on specified days. |
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| Carboplatin | Drug | Specified dose on specified days. |
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| Surgery | Procedure | Patients with resectable tumor after neoadjuvant therapy will be treated with surgery. |
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| 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 |
| 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 |
| Objective response rate (ORR) | ORR is defined according to the RECIST v1.1 criteria. | 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 |
| Treatment-related adverse event (TRAE) | TRAE is defined and classified according to NCI-CTCAE v5.0 in all participants. | 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 |
| ID | Term |
|---|---|
| C000632826 | sintilimab |
| C520255 | 130-nm albumin-bound paclitaxel |
| D016190 | Carboplatin |
| D013514 | Surgical Procedures, Operative |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
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