Orient: Multiple breakthrough pathways for innovative drugs; domestic innovation reshapes new standards.

Orient released a research report stating that the WCLC conference further validates that domestic innovative drugs in the lung cancer field have gradually progressed from early single-arm data to randomized controlled trials, global development, and frontline expansion. The lung cancer treatment landscape is evolving from being dominated by traditional chemotherapy and first-generation IO to multi-pathway competition involving ADCs, second-generation IO, and next-generation targeted therapies. It is recommended to focus on companies with differentiated efficacy, safety, and global development potential. Orient's main points are as follows: SCLC: The B7-H3 ADC era has arrived Both the TAISHAN-302 and ARTEMIS-008 Phase III studies achieved positive results. YL201 and HS-20093 significantly improved PFS and OS compared to topotecan, with an OS HR of 0.46 in both studies. B7-H3 ADC is expected to become the new standard therapy for relapsed SCLC. In addition, YL201 combined with serplulimab in first-line treatment of ES-SCLC achieved an ORR of 85.4%, and DB-1311 combined with pumitamig achieved a first-line ORR of 92.3% in SCLC. B7-H3 ADC is expanding from second-line monotherapy to first-line combination with immunotherapy. The bank believes that the realization of Phase III survival benefits propels B7-H3 ADC to become an important force in changing the SCLC treatment landscape, and subsequent global validation and frontline development are expected to further unlock clinical value. non-AGA NSCLC: First-line treatment competition intensifies HARMONi-2 updated OS results. Ivonescimab extended mOS in PD-L1-positive NSCLC patients from 22.6 months to 30.8 months compared to pembrolizumab (HR=0.73, P=0.009), driving PD-1/VEGF bispecific antibodies from PFS superiority to further achieving OS benefit. Meanwhile, RC148 combined with chemotherapy achieved cORR of 76.7% and 72.4% in squamous and non-squamous carcinoma, respectively. LBL-024 combined with chemotherapy achieved an overall ORR of 71.0%. ADC combined with immunotherapy regimens such as SYS6010 and YL201 also disclosed positive data. The bank believes that first-line treatment for non-AGA NSCLC is expanding from traditional IO monotherapy or immuno-chemotherapy to multi-mechanism combination regimens such as second-generation IO combined with chemotherapy and ADC combined with immunotherapy. Second-generation IO and ADC will jointly drive continuous iteration of first-line treatment standards. AGA NSCLC: Positive progress in EGFR and KRAS In the EGFR mutation field, updated HARMONi data showed that ivonescimab combined with chemotherapy achieved mOS of 16.8 months in patients previously treated with third-generation EGFR-TKI (HR=0.76), with consistent benefit trends in Asian and Western populations; Iza-bren at 2.5mg/kg achieved cORR of 29.6% in EGFR-TKI-treated patients. In the KRAS mutation field, HS-10370 first-line combination regimen achieved ORR of 81.5%; GFH375 achieved cORR and mPFS of 52.1% and 8.3 months, respectively, in treated KRAS G12D-mutant NSCLC; QLC1101 also showed preliminary antitumor activity. The bank believes that the landscape after third-generation TKI resistance is changing, and second-generation IO and ADC are expected to become new options; KRAS-mutant NSCLC is developing along two paths: G12C-targeted drugs moving toward first-line combination, and G12D inhibitors accelerating later-line clinical validation. Risk warnings Risk of innovative drug R&D failure; risk of intensified market competition; risk of innovative drug commercialization, etc.