AstraZeneca has released findings from two Phase III studies of Ultomiris (ravulizumab) in thrombotic microangiopathy following haematopoietic stem cell transplant (HSCT-TMA) and sonesitatug vedotin (Sone-Ve) in advanced gastric and gastroesophageal junction (GEJ) cancers.
In the global ALXN1210-TMA-313 Phase III trial, Ultomiris failed to achieve statistical significance for event-free survival through 26 weeks when compared to placebo in adults and adolescents, aged 12 years or above, with HSCT-TMA.
The primary endpoint measured the time from randomisation to TMA-related clinical worsening or death. A trend toward treatment benefit was observed at 26 weeks, though this did not reach the pre-specified level of statistical significance.
AstraZeneca said discussions with health authorities regarding the interpretation of data, including the use of real-world evidence, are ongoing.
In contrast, Ultomiris showed a clinically meaningful overall survival rate in paediatric patients with HSCT-TMA.
Data from the ALXN1210-TMA-314 open-label Phase III study revealed that overall survival was 87.2% at 26 weeks and 73.4% at 52 weeks.
Regulatory filings for Ultomiris in this indication are advancing, supported by data from ALX-TMA-502, an external control study.
The safety profile of Ultomiris across both ALXN1210-TMA-313 and ALXN1210-TMA-314 was observed to be consistent with existing data.
Ultomiris holds orphan drug designation in Japan and the US for HSCT-TMA, as well as breakthrough therapy designation from the US Food and Drug Administration (FDA) for paediatric patients with HSCT-TMA.
Separately, AstraZeneca reported that the CLARITY-Gastric01 global Phase III trial showed Sone-Ve, a Claudin 18.2 (CLDN18.2)-targeting antibody drug conjugate, achieved a statistically significant and highly clinically meaningful overall survival improvement.
This benefit was observed in the second and later-line treatment setting for patients with CLDN18.2-positive advanced gastric, GEJ, or oesophageal adenocarcinoma.
The improvement was seen when compared to investigator’s choice of therapy.
The trial met its dual primary endpoint of overall survival in third and later-line settings and a key secondary endpoint in second and later-line patients.
For the other dual primary endpoint, progression-free survival in the overall population, the trial showed a trend toward improvement without reaching statistical significance. Sone-Ve’s safety profile was consistent with earlier findings, with no new safety signals reported.
AstraZeneca oncology haematology R&D executive vice-president Susan Galbraith said: “Sone-Ve has the potential to reshape the treatment of gastric cancer by replacing classic chemotherapy with this novel targeted antibody drug conjugate to improve outcomes for patients.”
Sone-Ve has received orphan drug designation in the US and EU for gastric and GEJ cancers, as well as breakthrough designation in China for the second-line treatment of gastric cancer.
