SYS6010 Versus Docetaxel for Previously Treated EGFR Wild-type NSCLC: Phase Ⅲ

This is a randomized, open-label, multicenter, Phase III clinical study designed to evaluate the efficacy and safety of SYS6010 compared with docetaxel in participants with locally advanced or metastatic EGFR wild-type nsq-NSCLC who have failed standard therapy. Approximately 506 participants will be enrolled and randomized 1:1 to receive either SYS6010 or docetaxel. Randomization will be stratified by: (1) brain metastases (yes vs no) and (2) EGFR high expression (yes vs no). EGFR protein expression will be assessed by immunohistochemistry (IHC). Key eligibility criteria include: age ≥18 years; histologically or cytologically confirmed locally advanced or metastatic nsq-NSCLC; and EGFR mutation negative confirmed for the EGFR wild-type population. For participants who are driver gene-negative, prior therapy must have included immunotherapy and platinum-based chemotherapy ± anti-angiogenic therapy with documented treatment failure. For participants who are driver gene-positive, prior therapy must have included appropriate targeted therapy for the driver alteration and platinum-based chemotherapy, with treatment failure. The study includes a screening/baseline period, treatment period, safety follow-up (30 days after the last dose), PFS follow-up, and survival follow-up. Study Treatments: SYS6010: intravenous infusion 4.5 mg/kg Q3W. Docetaxel: intravenous infusion 75 mg/m² Q3W. Treatment will continue until meeting any protocol-defined treatment discontinuation criteria. Dose modifications may include dose interruption, dose reduction, and permanent discontinuation. Safety Assessments: Safety will be assessed from informed consent through 30 days after the last dose, including collection of all adverse events (AEs), clinical symptoms, vital signs, and laboratory abnormalities, and assessment of relationship to study treatment. Safety-related examinations (e.g., physical examination, ECOG performance status, laboratory tests) will be performed during screening/baseline and throughout treatment. Efficacy Assessments: Tumor response will be evaluated per RECIST v1.1. The first post-randomization tumor assessment will occur at 6 weeks (+7 days). Subsequent assessments will be performed every 6 weeks (±7 days) through Week 54 (excluding the first assessment), and every 12 weeks (±7 days) from Week 55 onward, and at the end of treatment if no assessment has been performed within the prior 4 weeks. Participants who discontinue treatment prior to disease progression will enter PFS follow-up until disease progression, initiation of new anticancer therapy, death, loss to follow-up, or withdrawal (whichever occurs first). Pharmacokinetics and Immunogenicity: Participants in the SYS6010 arm will undergo blood sampling for pharmacokinetics (PK) and immunogenicity assessments during the study.