阿斯利康在ESMO公布sone-ve胃癌ADC详细数据：OS显著获益但PFS未达标，管理层坚称足以申报

AstraZeneca executives were adamant that detailed data from a phase 3 study of the pharma’s next-generation antibody-drug conjugate (ADC) are “robust” enough to take to regulators, despite the trial failing to meet a key endpoint.
The company evaluated sonesitatug vedotin (sone-ve) in 594 patients with second-line or later advanced or metastatic Claudin 18.2-positive gastroesophageal carcinoma. AstraZeneca disclosed back in July that the study met one of its dual primary endpoints, overall survival (OS), while missing the other, progression-free survival (PFS) as assessed by blinded independent central review (BICR).
AstraZeneca presented the detailed data Sunday during a presidential symposium at the European Society for Medical Oncology (ESMO) Congress in Madrid. The results showed that median OS for patients receiving sone-ve in the third-line or later setting was 10 months, double the five months for patients receiving an investigator’s choice of therapy. In the intent-to-treat population, median OS was 10.6 months and 6.4 months, respectively.


In contrast, median PFS as assessed by BICR was 4.2 months for patients receiving sone-ve, barely above the 3.8 months for the control group.
Susan Galbraith, Ph.D., the pharma’s head of oncology hematology R&D, pointed out that PFS can be harder to measure in gastric cancer due to diffuse peritoneal spread, in which cancer cells break away from the primary tumor and implant on the lining of the abdominal cavity.
“When you're doing a blinded, independent central review, the people that are doing that obviously don't have the other clinical context,” Galbraith told Fierce during a briefing with journalists.

Instead, AstraZeneca has been reassured by the investigator-assessed PFS results, which showed a median of 4.4 months for the sone-ve group versus three months for the control group.
“So we see an enhanced response rate, we see an improvement in the investigator assessment of progression-free survival, and a very clinically meaningful overall survival, which is the key endpoint that I think will be important from a regulatory perspective,” Galbraith said.
In fact, the OS benefit in the trial was a “very similar level of benefit to what we saw with Enhertu in the DESTINY-Breast04 dataset,” added Galbraith, referring to the landmark trial that set the ADC on its path to blockbuster success.
While sone-ve is already undergoing other phase 3 studies in the first-line setting, Galbraith said AstraZeneca believes the “dataset that we've got is robust enough to take it to regulators.”
Still, sone-ve could have a fight on its hands. Takeda came to ESMO armed with data from a phase 3 win for its own Claudin 18.2-targeted ADC, dubbed arcotatug tavatecan.
AstraZeneca’s trial marks the first global phase 3 study of a Claudin 18.2-targeted ADC, while Takeda’s data came from China and Japan.
Galbraith also pointed out key differences between the rival treatments, with arcotatug tavatecan using a topoisomerase I inhibitor-based payload, while sone-ve uses a vedotin payload.
“So there is that difference,” she said. “But I think, again, on the OS—we are discussing with regulators. I think we're in a good position.”
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