Southwest Securities: Driver Gene-Negative NSCLC Topic — The Next Generation Treatment Paradigm - Bispecific Antibodies, IO+ADC

Driver Gene-Negative refers to the absence of detectable actionable driver gene mutations in tumor samples, accounting for 31% of newly diagnosed NSCLC patients in both China and the U.S. Based on current guidelines in China and the U.S., first-line treatment for advanced driver gene-negative NSCLC primarily relies on PD-(L)1 ± chemotherapy regimens. We estimate that by 2030, the market size for immunotherapy drugs used in first-line treatment of advanced driver gene-negative NSCLC will be approximately 7.5 billion yuan in China and 18 billion yuan in the U.S.

From the perspective of clinical guidelines, PD-(L)1 drugs represented by pembrolizumab and atezolizumab, with or without chemotherapy, have comprehensively covered first-line and subsequent treatments for driver gene-negative patients, maintaining a stable clinical position. However, limitations remain over the long term: 1) IO resistance, with long-term efficacy plateauing (bispecific antibodies): Compared to traditional chemotherapy, immunotherapy combined with or without chemotherapy significantly improves long-term survival rates, but the 5-year survival rate drops to 10%-30%. Long-term treatment effects for patients with medium to low PD-L1 expression are gradually reaching a bottleneck. 2) Limited options for patients intolerant to chemotherapy, with few potent regimens available. Current evidence only supports the use of single-agent immunotherapy (e.g., atezolizumab or pembrolizumab) in patients with high PD-L1 expression (TPS≥50%). Patients with medium to low expression and those intolerant to chemotherapy lack clinically effective regimens (IO+ADC).