Orient Securities has released a research report stating that the latest WCLC conference further validates that domestic innovative drugs in lung cancer have progressed from early single-arm data to randomized controlled trials, global development, and frontline expansion stages. The lung cancer treatment landscape is evolving from traditional chemotherapy and first-generation immunotherapies toward multi-path competition involving ADCs, second-generation immunotherapies, and next-generation targeted therapies. The firm recommends focusing on companies developing drugs with differentiated efficacy, safety profiles, and global development potential.

Key viewpoints from Orient Securities:

SCLC: The Era of B7-H3 ADCs Has Arrived

Both the TAISHAN-302 and ARTEMIS-008 Phase III studies achieved positive results, with YL201 and HS-20093 significantly improving progression-free survival and overall survival compared to topotecan. Both studies reported an OS hazard ratio of 0.46, positioning B7-H3 ADCs as a potential new standard of care for relapsed small cell lung cancer. Additionally, YL201 combined with serplulimab achieved an ORR of 85.4% in first-line treatment of extensive-stage SCLC, while DB-1311 combined with pumitamig reached a first-line ORR of 92.3% in SCLC, demonstrating that B7-H3 ADCs are expanding from second-line monotherapy to first-line combination regimens with immunotherapies. The firm believes that the realization of survival benefits in Phase III trials establishes B7-H3 ADCs as a significant force in reshaping the SCLC treatment landscape, with subsequent global validation and frontline development expected to further unlock clinical value.

Non-Squamous NSCLC: Intensifying Competition in First-Line Treatment

Updated OS results from the HARMONi-2 trial showed that ivonescimab extended median overall survival in PD-L1 positive NSCLC patients from 22.6 months to 30.8 months compared to pembrolizumab, with a hazard ratio of 0.73 and a p-value of 0.009, advancing the PD-1/VEGF bispecific antibody from PFS superiority to confirmed OS benefit. Meanwhile, RC148 combined with chemotherapy achieved confirmed ORRs of 76.7% and 72.4% in squamous and non-squamous carcinoma, respectively, while LBL-024 combined with chemotherapy showed an overall ORR of 71.0%. ADC plus immunotherapy regimens such as SYS6010 and YL201 also disclosed encouraging data. The firm believes that first-line treatment for non-squamous NSCLC is expanding from traditional immunotherapy monotherapy or immunochemotherapy toward multi-mechanism combination approaches including second-generation immunotherapy plus chemotherapy and ADC plus immunotherapy, with both second-generation immunotherapies and ADCs jointly driving continuous iteration of first-line treatment standards.

EGFR-Mutant and KRAS-Mutant NSCLC: Positive Progress

In the EGFR mutation segment, updated HARMONi data showed that ivonescimab combined with chemotherapy achieved a median OS of 16.8 months in patients previously treated with third-generation EGFR-TKIs, with a hazard ratio of 0.76, and consistent benefit trends observed across Asian and Western populations. Iza-bren demonstrated a confirmed ORR of 29.6% at the 2.5mg/kg dose in EGFR-TKI pretreated patients. In the KRAS mutation segment, the first-line combination regimen of HS-10370 achieved an ORR of 81.5%, while GFH375 showed a confirmed ORR of 52.1% and median PFS of 8.3 months in pretreated KRAS G12D mutant NSCLC patients. QLC1101 also exhibited preliminary antitumor activity. The firm believes that the post-third-generation TKI resistance landscape is evolving, with second-generation immunotherapies and ADCs emerging as new options. KRAS-mutant NSCLC is advancing along two pathways: G12C targeted therapies moving toward first-line combination use, and G12D inhibitors accelerating later-line clinical validation.

Risk Factors

Risks include failure of innovative drug research and development, intensifying market competition, and commercialization risks associated with innovative drugs.