Exploratory Study of NK510 Combined With PD-1 Blockade in the Treatment of Relapsed and Refractory Advanced NSCLC
This study assesses the safety and efficacy of NK510 combined with PD-(L)1 inhibitors for relapsed/refractory advanced NSCLC, with two administration routes: intravenous infusion and intrapleural perfusion for malignant pleural effusion. Eligible patients need confirmed measurable lesions; intravenous cohort requires EGFR/ROS1/ALK negativity and disease progression after PD-(L)1 inhibitor treatment, while intrapleural cohort accepts targeted therapy-resistant patients with ≥500ml pleural effusion, and the treatment's safety, efficacy and immune microenvironment changes will be evaluated.
• Age ≥ 18 years, male or female.
• For dose expansion group (Group A/B/C):
⁃ A. EGFR mutation-negative, ROS1-negative, and ALK-negative; unresectable and non-radiotherapeutic stage III or IV, locally advanced, recurrent or metastatic NSCLC.
⁃ B. Disease progression after ≥4 courses of PD-(L)1 blockade ± chemotherapy.
• For pleural perfusion group (Group D1/D2): Advanced NSCLC with malignant pleural effusion ≥500ml (confirmed by B-ultrasound or CT); patients with driver gene-positive and resistant to targeted therapy are acceptable.
• At least one CT or MRI measurable lesion according to RECIST v1.1.
• ECOG performance status 0-2.
• Expected survival ≥3 months.
• All toxicities from previous anti-tumor therapy (except alopecia and fatigue) resolved to grade 1 (CTCAE v5.0) or baseline; subjects with long-term sequelae from previous therapy (e.g., neuropathy after platinum-based therapy) are acceptable.
• Fertile females must be non-lactating and have a negative serum pregnancy test within 1 week before enrollment; all subjects (male or female) must agree to use contraception from signing informed consent until 6 months after the last NK510 infusion.
• Able to comply with the study protocol and follow-up procedures.
• Voluntarily sign the informed consent form.