A Randomized, Open-Label, Multicenter, Phase 3 Study Evaluating the Efficacy and Safety of IBI363 Versus Docetaxel in Participants With Unresectable Locally Advanced or Metastatic Squamous Non-Small Cell Lung Cancer With Disease Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy
Phase: 3 Type: Randomized, open-label, multi-regional, multi-center Population: Adults with advanced/metastatic squamous Non Small Cell Lung Cancer (NSCLC), post-progression on platinum chemo + PD-1/PD-L1 immunotherapy Enrollment: \ 600 participants Randomization: 1:1 (IBI363 vs. docetaxel) Stratification factors: 1. Primary vs. acquired IO resistance 2. Concurrent vs. sequential prior chemo-immunotherapy 3. Region (Asia vs. non-Asia) Treatment Arms: 1. IBI363 Arm (Investigational Drug): Priming dose: 0.1 mg/kg on Day 1 of Cycle 1 (C1D1) Intended dose: 3 mg/kg every 3 weeks (Q3W) starting Day 8 of Cycle 1 (C1D8) Cycle duration: 28 days for Cycle 1, then 21 days from Cycle 2 onward Dose adjustments: Up to 2 reductions (1.5 mg/kg or 1 mg/kg Q3W) allowed for adverse events (AEs) Re-priming protocol: Required if delays in dosing exceed defined thresholds (e.g., \>10 days post-priming or ≥5 weeks since last dose) 2. Control Arm (Docetaxel): 75 mg/m² every 3 weeks (Q3W), starting from C1D1 21-day cycle duration Dose Reduction: as per label
• Willing to sign the written informed consent form and be able to comply with the visit schedule and related procedures specified in the protocol.
• Male or female participants must be at least 18 years old or the legal age of majority in their country, whichever is greater.
• Have locally unresectable advanced or metastatic histologically or cytologically confirmed squamous NSCLC Note: Mixed small cell carcinoma, or other pathological components are excluded.
• Resistant or refractory to systemic anti-tumor therapy, including platinum-based doublet chemotherapy and primary or secondary resistance to anti-PD-1/PD-L1 monoclonal antibody given in combination or sequentially; or given as neoadjuvant and/or adjuvant therapy, which will be considered first-line treatment if the disease has recurred or progressed during such treatment or within 6 months after discontinuation.
• Radiographic progression per RECIST v1.1 during or within 6 months after discontinuation of anti-PD-1/PD-L1 monoclonal antibody treatment.
• Agree to provide archival (collected within 2 years before signing the informed consent form if biopsy cannot be performed or participant refuses fresh biopsy) tumor tissue specimens for PD-L1 expression level testing and exploratory analysis of other biomarkers.
• Have at least one measurable lesion (target lesion) by computed tomography (CT) or magnetic resonance imaging (MRI) according to RECIST v1.1. Lesions that have previously received radiotherapy or intratumoral injection can be used as measurable lesions if they show progression after treatment (either tissue confirmed or more than 3 months after treatment) as per RECIST v1.1.
• ECOG PS score of 0 or 1.
• Expected survival time ≥ 3 months.
⁃ Women of childbearing potential (WOCBP) or men with female partners of childbearing potential must agree to take effective contraceptive measures during the entire course of treatment and for 6 months after the last dose of study treatment.
⁃ Lactating women must agree to strictly abstain from breastfeeding during the entire Treatment Period and for 6 months after the treatment.