AstraZeneca has reported that its investigational antibody-drug conjugate (ADC) sonesitatug vedotin extended overall survival in patients with advanced gastric or gastroesophageal cancer who had received at least two previous treatments. However, the Phase III study did not meet its other primary objective of progression-free survival, leaving questions about the drug’s potential positioning in a competitive treatment landscape.

Data from the 532-patient trial were presented on October 25 at the European Society for Medical Oncology (ESMO) congress in Madrid. Patients receiving sonesitatug vedotin, also known as sone-ve, achieved a median overall survival of 10 months, compared with five months among those treated with physician’s choice of chemotherapy. This represented a 53% reduction in the risk of death.

Susan Galbraith, executive vice president of oncology hematology research and development at AstraZeneca, describes the five-month improvement as clinically meaningful for a patient population with limited treatment options.

The overall survival result could strengthen the drug’s commercial prospects, although the failure to achieve statistical significance for progression-free survival presents a challenge. AstraZeneca has estimated that the medicine could eventually generate peak annual sales of $3 billion to $5 billion, while analyst expectations have been more conservative, at around $1 billion.

Sonesitatug vedotin belongs to the ADC drug class, which combines an antibody designed to recognize a particular cellular target with a potent therapeutic payload. The approach aims to deliver treatment preferentially to cancer cells while limiting exposure to healthy tissue.

The trial enrolled patients whose tumors expressed claudin 18.2, a protein found on the surface of certain cancer cells. At least 25% of tumor cells had to express the protein for patients to qualify. By comparison, the approved treatment targeting claudin 18.2 uses a higher expression threshold of 75%.

Galbraith says the broader eligibility criteria could potentially expand the population able to receive treatment and support evaluation of the drug in earlier stages of therapy.

A separate study involving more than 2,000 patients is already investigating sonesitatug vedotin in an earlier treatment setting.

Serious adverse events were reported in 36.4% of patients receiving sonesitatug vedotin, compared with 44.8% of those treated with chemotherapy. Gastrointestinal-related side effects, however, occurred more frequently with the investigational drug, affecting 11.1% of patients versus 6.3% in the chemotherapy group.

The results arrive as pharmaceutical companies compete to develop therapies against claudin 18.2. Takeda and Innovent Biologics are developing a rival candidate, IBI343, which met its progression-free survival objective in a late-stage study. HSBC analysts noted that AstraZeneca’s failure to achieve statistical significance on that endpoint makes direct comparisons between the programs more difficult.

AstraZeneca is also pursuing combination strategies for sonesitatug vedotin. In September, the company agreed to invest $2 billion in Summit Therapeutics and test the ADC alongside Summit’s bispecific antibody ivonescimab.

For more information, visit www.astrazeneca.com.