AstraZeneca executives told Fierce they are “very confident” in the pharma’s in-house pipeline of antibody-drug conjugates (ADCs) despite scrapping two candidates that underperformed in the clinic.
They included an EGFR-cMET TOP1i ADC called tilatamig samrotecan that was being evaluated in a phase 1 study of 403 patients with advanced solid tumors like non-small cell lung cancer, head and neck squamous-cell carcinoma and colorectal cancer.
The trial kicked off in early 2023, but AstraZeneca disclosed in its second-quarter earnings documents that the company has now discontinued the study due to unimpressive pharmacokinetics and pharmacodynamics.
AstraZeneca removed tilatamig samrotecan, which had made it into phase 2 development, from its pipeline alongside another in-house ADC dubbed AZD4360.
The CLDN18.2 TOP1i ADC was undergoing a phase 1 study in 117 patients with advanced or metastatic Claudin 18.2-expressing pancreatic ductal adenocarcinoma, gastric/gastroesophageal junction cancer or biliary tract cancer.
This study had launched in the second quarter of 2025, according to AstraZeneca’s earnings documents, but has now been terminated “due to efficacy.”
AstraZeneca is a major player in the ADC space thanks to the blockbuster Enhertu, and its follow-up Datroway, both of which emerged from a collaboration with Daiichi Sankyo. But executives told Fierce last year that a key focus of the company’s strategy involves “a conscious effort to invest significantly” in its internal pipeline.
This has led AstraZeneca to develop its own linker payload and surface marker library, so it has multiple options to combine the right targets with the right warheads. These in-house efforts include a FRα-targeted ADC called torvutatug samrotecan and a B7-H4-directed ADC called puxitatug samrotecan, which are both in phase 3 development.
On an earnings call with journalists this morning, AstraZeneca Chief Financial Officer Aradhana Sarin pointed out that the company has “half a dozen plus ADCs which are homegrown, which are in the clinic.”
“We are very confident in that,” Sarin told Fierce.
Meanwhile, AstraZeneca CEO Pascal Soriot used the scrapped ADCs as an example of why it’s “very important … to fail fast in the early phase.”
“That's what we try to do,” Soriot told Fierce on the call. “When we are positive, we move into phase quickly. But we want to fail fast so we can redeploy resources to other projects.”
There was better news for AstraZeneca’s in-licensed ADCs this morning, with the company announcing that sonesitatug vedotin, a therapy licensed from KYM that’s also known as sone-ve, had hit the key goals of a phase 3 gastric cancer study. The trial met the dual primary endpoints of overall survival in third and later-line treatment and progression-free survival in Claudin 18.2-positive advanced gastric cancers.
Susan Galbraith, Ph.D., the pharma’s head of oncology hematology R&D, said in a release that sono-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.”
“These transformative results from the first phase 3 readout for sone-ve, together with our broad development programme, highlight the potential for sone-ve to become an important new medicine in CLDN18.2-positive cancers,” Galbraith added.
AstraZeneca disclosed a couple other changes further back in its pipeline this morning. They included calling time on an inhaled JAK1 inhibitor that was being assessed in a pair of phase 2 studies for asthma. AstraZeneca confirmed this morning that both trials had been discontinued due to efficacy.
The final drug in the pharma’s second-quarter clearout was AZD2068, a EGFR/cMET actinium radioconjugate that was being evaluated in a phase 1 study of 110 patients with solid tumors. AstraZeneca said it had ended the program due to disappointing pharmacokinetics and pharmacodynamics.