In the era of immunotherapy 2.0, the industry is diverging into two major technological pathways, according to a research report from Orient Securities Company Limited. The first pathway involves second-generation bispecific antibodies (such as PD1/VEGF and PD-1/IL2) combined with chemotherapy, represented by drugs like ivonescimab and IBI363. This approach offers advantages across all PD-L1 expression subgroups, particularly showing significant benefit for patients with PD-L1 negative tumors. The second pathway combines Antibody-Drug Conjugates (ADCs) with PD-1 inhibitors, with Sac-TMT plus Keytruda (pembrolizumab) serving as a benchmark, achieving a leap in efficacy for PD-L1 positive patients.

At the recent ASCO conference, domestic innovative drugs made significant breakthroughs, demonstrating strong competitiveness. The report suggests focusing on innovative pharmaceutical companies with international competitive advantages. Relevant companies mentioned include AKESO (09926, not rated), SKB BIO (06990, not rated), and INNOVENT BIO (01801, not rated). The main points from Orient Securities are as follows:

First-Line NSCLC Treatment Enters New Iteration Cycle with Second-Generation IO and ADC+IO Therapies

Three major clinical datasets from domestic innovative drugs presented at the ASCO conference indicate that the first-line gold standard for NSCLC, traditionally PD-1 inhibitors with or without chemotherapy, is facing systematic replacement. While domestic drug development largely followed overseas PD-1 drugs in the immunotherapy 1.0 era, it has now rapidly advanced to lead the immunotherapy 2.0 era, potentially creating a comprehensive paradigm shift in the multi-billion-dollar lung cancer treatment market.

Ivonescimab (PD-1/VEGF Bispecific) Shows Promise in Reshaping First-Line Squamous Cell Carcinoma Standard

The conference disclosed key interim overall survival (OS) data from the HARMONi-6 study. The "ivonescimab + chemotherapy" regimen demonstrated superior progression-free survival (PFS) and OS compared to "tislelizumab + chemotherapy" in first-line treatment for driver gene-negative lung squamous cell carcinoma. The median PFS was 11.1 months (versus 6.9 months in the control group, HR=0.60), and the median OS was 27.9 months (versus 23.7 months in the control group, HR=0.66), with the survival curves continuing to separate. This study is the first global Phase III trial in lung cancer where an "IO + chemotherapy" combination achieved significant benefit in both primary endpoints in a head-to-head comparison, potentially establishing a new first-line standard for squamous cell carcinoma in China. Looking ahead, the final PFS data from the global Phase III trial for ivonescimab (HARMONi-3) is expected to be disclosed in the second half of the year, and whether it can replicate the positive results globally is highly anticipated.

Impressive First-Line Data for Sac-TMT (TROP2-ADC) Plus Keytruda

Data from the Phase III OptiTROP-Lung05 study for SKB BIO's Sac-TMT combined with pembrolizumab (Keytruda) was outstanding. For PD-L1 positive advanced NSCLC, the PFS hazard ratio (HR) was as low as 0.35 (p<0.0001), and the objective response rate (ORR) reached 70.2% (compared to 42% for Keytruda monotherapy). The advantage was particularly pronounced in the PD-L1 1-49% low-to-moderate expression subgroup (HR=0.28). Overall survival (OS) also showed a clear trend towards benefit (HR=0.55), addressing the efficacy gap of Keytruda monotherapy in patients with low-to-moderate PD-L1 expression. This study is the first globally to achieve positive Phase III results for an ADC+IO combination in first-line NSCLC, potentially reshaping the first-line treatment landscape for PD-L1 positive NSCLC.

IBI363 (PD-1/IL2 Bispecific) Makes Rapid Progress, Pioneering New NSCLC Treatment Path

INNOVENT BIO's IBI363 presented Phase I clinical data at the conference. Notably, the study is the first to validate a differentiated dosing strategy of "high initial dose to ignite the immune system, followed by low maintenance dose." The preferred (3→1.5) mg/kg regimen combined with chemotherapy achieved an ORR of 86.4% and a disease control rate (DCR) of 100% in PD-L1 negative/low expression refractory patients. Efficacy was superior to the traditional Keytruda + chemotherapy regimen across both squamous and non-squamous carcinoma subgroups, addressing the challenge of treating PD-L1 "cold" tumors and establishing it as an important candidate for the next generation of bispecific antibodies.

The report also highlights risk factors including the potential for innovative drug R&D failure, intensifying market competition, and risks associated with the commercialization of innovative drugs.