Phase III readouts for two CLDN18.2 ADCs: Sone-Ve has broader coverage, while IBI343 delivers deeper efficacy
In previously treated patients with gastric and gastroesophageal junction cancer, Sone-Ve showed a notable overall survival benefit in the third-line and later setting, but the primary progression-free survival endpoint in the overall second-line and later population did not meet the prespecified statistical threshold; IBI343 met both primary endpoints in a more strictly selected population.
Original source：Goldman SachsFirst published on Unhidea：Original source date：
Key takeaway
Goldman Sachs believes the two Phase III data sets support the efficacy of CLDN18.2 ADCs in previously treated gastric cancer: Sone-Ve’s potential advantage is its broader expression range, while IBI343 demonstrated deeper responses and progression-free survival benefit in a more strictly selected population.
Where does Sone-Ve’s survival benefit come from?
For Sone-Ve from Claris Biotherapeutics and AstraZeneca, median overall survival among third-line and later patients was 10.0 months, versus 5.0 months in the control group, with a hazard ratio for death of 0.47. In the overall second-line and later population, median overall survival was 10.6 months versus 6.4 months in the control group.
However, progression-free survival as assessed by blinded independent review, one of the co-primary endpoints in the overall second-line and later population, was 4.2 months versus 3.8 months in the control group, with a p-value of 0.053, narrowly missing the prespecified statistical threshold. The corresponding figures in the third-line and later subgroup were 4.1 versus 2.7 months.
The overall survival hazard ratio in the second-line subgroup was 0.88, numerically weaker than the 0.47 seen in the third-line and later setting. Goldman Sachs believes the overall benefit was driven primarily by later-line patients, but cautions against overinterpreting subgroup analyses; positioning in earlier lines requires further study.
Why could the expression range be an advantage for Sone-Ve?
The trial enrolled patients with CLDN18.2 membrane staining in at least 25% of tumor cells, regardless of staining intensity. In the subgroup with an expression proportion of at least 75%, median overall survival was 10.6 months versus 6.4 months in the control group; in the subgroup with expression from 25% to less than 75%, the figures were 10.5 and 6.2 months, respectively.
Goldman Sachs believes the survival benefit also observed in the lower-expression subgroup is a potential differentiator for Sone-Ve relative to programs with stricter selection. However, different trials use different assays, so expression-proportion thresholds cannot be used to directly calculate the number of patients potentially covered.
On safety, the incidence of grade 3 or higher treatment-related adverse events in the Phase III trial was 36.4%, versus 44.8% in the control group; 5.0% discontinued treatment due to adverse events.
How strong is IBI343’s efficacy, and what should be considered when comparing it?
The Phase III trial of IBI343 from Innovent Biologics and Takeda enrolled patients who had previously received 2 to 4 systemic therapies and whose tumors had CLDN18.2 immunohistochemistry scores of 2+ or higher in at least 75% of tumor cells. Both primary endpoints were met.
With longer follow-up, median progression-free survival was 7.1 months in the IBI343 group versus 3.1 months in the chemotherapy group; median overall survival was 10.2 and 6.9 months, respectively, and the confirmed objective response rate was 37.4% versus 7.7%.
Goldman Sachs believes IBI343 showed more pronounced response and progression-free survival benefits, but the trials differed in assays, biomarker definitions and the distribution of treatment lines, so the figures cannot be used as a direct head-to-head comparison between the drugs.
The incidence of grade 3 or higher treatment-related adverse events was 47.4% in the IBI343 group versus 55.9% in the chemotherapy group, primarily hematologic toxicity; 1.7% discontinued treatment due to treatment-related adverse events.
How could IBI343 broaden its opportunity next?
Innovent management said the company and Takeda plan to advance a global Phase III trial in first-line gastric cancer, potentially including patients with lower expression levels. Goldman Sachs believes that maintaining response and progression-free survival performance while expanding the population would strengthen its competitive position.
Pancreatic ductal adenocarcinoma is another expansion path Goldman Sachs considers promising: a Phase III trial in third-line and later patients in China is underway, while first-line trials in China and globally are being planned, potentially extending the opportunity beyond the increasingly competitive gastric cancer field.
