Original source：Nomura International (Hong Kong) Ltd.First published on Unhidea：Original source date：
Key takeaway
The key differences among these clinical results are which treatments have demonstrated longer overall survival, which have so far mainly demonstrated delayed disease progression, and which comparator regimen each beat.
Which patients saw a breakthrough with Innovent’s IBI343?
Innovent’s CLDN18.2 ADC, IBI343, met both the overall survival (OS) and progression-free survival (PFS) endpoints in a phase III trial involving previously treated patients with CLDN18.2-positive gastric or gastroesophageal junction cancer. The results cover both longer survival and delayed disease progression.
Median overall survival with IBI343 monotherapy was 10.2 months, compared with 6.9 months for physician’s choice of chemotherapy; at the second interim analysis, median progression-free survival was 7.1 months versus 3.1 months in the control group. The benefit applies to a specific previously treated, biomarker-positive population.
Innovent’s other EGFR/B7H3 ADC, IBI3001, remains in phase I: the objective response rate among 53 evaluable patients was 30.2%, and Nomura considers the efficacy encouraging and the safety manageable. It provides an early signal of activity, at a different stage from the phase III survival evidence for IBI343.
Why was Akeso described as having “another win, but not an overwhelming one”?
In the phase III HARMONi-GI1 trial in first-line biliary tract cancer, ivonescimab plus chemotherapy was compared with durvalumab plus chemotherapy. The trial compared two combinations containing immunotherapy, a different benchmark from chemotherapy alone.
The trial met its primary overall survival endpoint: median overall survival was 14.9 months versus 12.1 months in the control group, with a hazard ratio of 0.75; median progression-free survival was 8.4 months versus 5.8 months, and the objective response rate was 53.8% versus 32.5%. Nomura assessed the results positively while characterizing the margin of victory as not overwhelming.
How does the evidence differ between Kelun’s two lung cancer results for the same drug?
Kelun-Biotech’s TROP2 ADC sac-TMT has a final overall survival analysis from OptiTROP-Lung04. In patients with EGFR-mutated non-small cell lung cancer after treatment with a tyrosine kinase inhibitor, median overall survival was 25.9 months versus 17.4 months with platinum-based chemotherapy, with a hazard ratio of 0.69.
OptiTROP-Lung06 targeted first-line, PD-L1-negative non-squamous non-small cell lung cancer. Median progression-free survival with sac-TMT plus pembrolizumab was 15.0 months versus 5.7 months with chemotherapy plus pembrolizumab, a statistically significant difference.
The positive implications of the two results have distinct limits: the former has shown a survival benefit, while the latter mainly confirms an advantage in disease control; its overall survival data are not yet mature, and a favorable trend has been observed so far. The trials also involved different patients and lines of treatment.
What has Hengrui’s breast cancer result demonstrated?
In the phase III HORIZON-Breast06 trial of Hengrui’s HER2 ADC SHR-A1811 in advanced HER2-low breast cancer, median progression-free survival reached 16.4 months versus 6.8 months in the chemotherapy group, with a hazard ratio of 0.27; the difference was statistically significant.
The result supports its efficacy in delaying disease progression; overall survival is currently showing a positive trend. The established progression-free survival advantage and the overall survival trend should therefore be considered separately when interpreting this advance.
