Stomach cancer drug cut death risk by 42% in late-stage trial, maker says

AstraZeneca says an experimental drug helped people with advanced stomach cancer live longer than standard treatment in a large trial. The drug, sonesitatug vedotin (shortened to Sone-Ve), cut the risk of death by 42% across all patients, with median survival of 10.6 months compared with 6.4 months for treatment chosen by their doctors¹. The results were presented on Sunday, 25 October, at the European Society for Medical Oncology congress in Madrid².

The trial also missed one of its two main goals: it did not clearly show that the drug slowed tumor growth². That mix of a strong survival result and a narrow miss is why analysts and doctors are reading the data with some care.

What happened

The trial, called CLARITY-Gastric01, enrolled 532 people with advanced or spreading cancer of the stomach, the gastroesophageal junction (where the stomach meets the food pipe), or the lower food pipe³. All had already been treated at least once. It ran at 175 centers in 19 countries across North America, Europe, South America and Asia³.

People were randomly assigned to Sone-Ve or to a treatment picked by their doctor, which included chemotherapies or targeted drugs accepted in their region². Sone-Ve is an antibody-drug conjugate: an antibody that seeks out a protein called claudin 18.2 on cancer cells, joined to a cell-killing drug, so the treatment is aimed at tumor cells³. Its cell-killing part is a drug called monomethyl auristatin E².

The evidence so far

The trial had two main goals. The first was survival in the 355 patients who had already had at least two earlier treatments². The second was progression-free survival, meaning how long people lived before their tumors grew, judged by independent reviewers across all 532 patients². Survival across all patients was a key secondary goal².

The results reported for each group:

• People with at least two prior treatments (main survival goal, met): median survival of 10.0 months on Sone-Ve versus 5.0 months, a 53% lower risk of death². After a year, 38.1% were alive on Sone-Ve versus 18.1%².
• All 532 patients (key secondary goal): median survival of 10.6 versus 6.4 months, a 42% lower risk of death². After a year, 42.6% were alive on Sone-Ve versus 27.8%⁴.
• Tumor growth by independent review (main goal, missed): 4.2 versus 3.8 months, with a p-value of 0.053, just above the usual 0.05 cutoff for a result to count as statistically significant².

When the treating doctors judged tumor growth instead, the figures were 4.4 versus 3.0 months, but that analysis was exploratory, meaning it was not one of the trial’s planned tests². AstraZeneca said that analysis fits better with the survival benefit¹.

On safety, serious treatment-related side effects occurred in 36.4% of people on Sone-Ve and 44.8% on the comparison treatments³. Stomach-related side effects were more common on Sone-Ve, at 11.1% versus 6.3%, Reuters reported⁵. The company said it saw no new safety concerns³.

The trial’s principal investigator, Rui-Hua Xu of Sun Yat-Sen University Cancer Center in Guangzhou, China, said:

“These are remarkable survival results for Sone-Ve in 2nd- and later-line metastatic gastric cancer, a disease where patients face a poor prognosis once initial therapy fails.”³

What it does not show yet

The missed tumor-growth goal is the main caution. One of the two main goals was not met on its own terms, and the survival results should be read with that in mind, medgadget.in noted². A commentator at the conference said the miss makes the drug’s role for people on their second treatment less certain, though it could become an important option for people further along⁶.

Other limits:

• The trial was open-label, meaning patients and doctors knew which treatment was given, though it was “sponsor-blinded”².
• The results reported in the sources come from a conference presentation and company statements. The sources do not describe a full journal paper.
• No response-rate figure, such as how often tumors shrank, was reported in the material medgadget.in read².
• Only people whose tumors carried enough of the target protein could join, so the results apply to that group¹.

Who is behind it

AstraZeneca runs the trial and is developing the drug, which it licensed from KYM Biosciences in March 2023². Most of the details and all the quotes above come from the company and its chosen lead investigator.

The company has a lot riding on it. AstraZeneca has said the drug could bring in $3 billion to $5 billion in peak yearly sales, while analysts’ estimates are closer to $1 billion, Reuters reported⁵. Analysts had expected a reduction in the risk of death to about 0.7 or lower on the standard scale, with a gain of at least two months; the result beat that⁵.

Susan Galbraith, who leads oncology research and development at AstraZeneca, told Reuters:

“A 5-month improvement in overall survival is very clinically significant in a difficult to treat patient population.”⁵

A month before the conference, AstraZeneca agreed to invest $2 billion in Summit Therapeutics and to test Sone-Ve together with Summit’s drug ivonescimab⁵.

How it fits the field

Stomach cancer is the fifth most common cancer worldwide and the fifth-leading cause of cancer deaths, with nearly one million new cases and about 650,000 deaths in 2024³. According to AstraZeneca, fewer than 20% of people with advanced stomach or junction cancer live beyond a year².

Claudin 18.2 is already a target for an approved treatment, but that treatment requires the protein on at least 75% of tumor cells. This trial let people in if at least 25% of their tumor cells carried it⁵. AstraZeneca estimates about 60% of stomach and junction cancers meet that lower bar³. Galbraith said the lower threshold could double the number of patients who could receive treatment⁵. The survival benefit looked similar in both groups: the risk of death on Sone-Ve, relative to the comparison, was 0.59 where 75% or more of cells carried the protein and 0.63 where 25% to under 75% did².

There is competition. Takeda and Innovent are developing a rival claudin 18.2 drug that met its tumor-growth goal in a late-stage trial; HSBC analysts said Sone-Ve’s miss makes the two harder to compare⁵. AstraZeneca also sells Enhertu, developed with Daiichi Sankyo, which is approved for a different type of advanced stomach cancer, one marked by the protein HER2⁴.

What to watch next

• A filing with regulators. AstraZeneca argues the data are strong enough to take to regulators⁶, and one summary of the coverage said the company is preparing to file⁷. As of 26 October, the company had not announced a filing date².
• Earlier use. A larger trial, CLARITY-Gastric02, is testing Sone-Ve as a first treatment for advanced stomach and related cancers³. Reuters described a study of more than 2,000 patients testing the drug earlier in treatment⁵.
• Other cancers. Smaller trials are testing the drug in pancreatic and bile duct cancers that carry claudin 18.2⁴.
• A full paper. A detailed publication would let outside experts check the survival analysis and the tumor-growth miss more closely.