Clinical trial NCT06837948: Neoadjuvant Chemotherapy Combined With Bispecific Antibody Versus Monoclonal Antibody in Locally Advanced NSCLC
Official title: Neoadjuvant Chemotherapy Combined With Bispecific Antibody Versus Monoclonal Antibody in Locally Advanced Non-Small Cell Lung Cancer: A Multicenter, Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Non-Small Cell Lung Cancer
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
First posted: 2025-02-20
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Pathologic complete response (PCR) rate
timeFrame: Up to 30 months
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: Up to 60 months
measure: Overall survival (OS)
timeFrame: Up to 60 months
measure: Major pathologic response (MPR) rate
timeFrame: Up to 30 months
measure: Objective response rate (ORR)
timeFrame: Up to 30 months
measure: R0 resection rate
timeFrame: Up to 30 months
measure: Treatment-related adverse event (TRAE)
timeFrame: Up to 30 months
measure: Health related quality of life (HRQol) composite
timeFrame: Up to 5 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
Study officials:
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
name: Peng Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
References: