e20507 Background: The combination of immunotherapy and antiangiogenic therapy represents a promising first-line strategy for NSCLC, supported by early clinical data showing favorable efficacy and safety. However, immunotherapy resistance remains a critical challenge. This study aimed to evaluate the efficacy and safety of cadonilimab, the first-in-class bispecific anti–PD-1/CTLA-4 antibody, combined with anlotinib, in patients with advanced NSCLC refractory to prior systemic therapy including anti–PD-(L)1 antibodies. Methods: Patients and Treatment: Eligible patients had unresectable locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC and had progressed on prior systemic therapy, including anti–PD-(L)1 agents. Patients received cadonilimab (10 mg/kg intravenously every 3 weeks) plus oral anlotinib (10 mg once daily in a 2-weeks-on/1-week-off schedule) per 21-day cycle for 4 to 6 cycles, followed by maintenance therapy until disease progression, unacceptable toxicity, completion of 24 months of treatment, or meeting other protocol-defined discontinuation criteria. Assessments: Tumor response was assessed regularly according to RECIST v1.1. Radiographic evaluations were performed every 6 weeks (±7 days) for the first 48 weeks, then every 12 weeks (±7 days) thereafter. For subjects who discontinued treatment for reasons other than progression or death, tumor assessments continued per schedule until subsequent progression, initiation of new antitumor therapy, or study withdrawal. Objective responses required confirmation ≥4 weeks after the initial documentation. Results: At the January 2026 data cutoff, 33 evaluable patients had a median follow-up of 11.0 months (95% CI: 7.2–13.2). The confirmed ORR was 24.2%, and the disease control rate (DCR) was 75.8%. The 1-year overall survival (OS) and PFS rates were 77.6% and 55.5%, respectively. Notably, the PFS curve plateaued at 55.5% and remained stable through the maximum follow-up of 24.0 months. Treatment-related adverse events (TRAEs) occurred in 30.3% (10/33) of patients, with Grade ≥3 TRAEs observed in 9.1% (3/33). No Grade 4 or 5 TRAEs were reported. Mucocutaneous reactions were the most frequently reported TRAEs. Conclusions: This preliminary analysis suggests that cadonilimab combined with anlotinib shows promising antitumor activity and manageable safety in advanced NSCLC patients after systemic therapy failure and resistance to anti–PD-(L)1 antibody treatment.Enrollment is ongoing.
Ye et al. (Thu,) studied this question.