A phase 3 study of AstraZeneca’s ceralasertib has missed its primary endpoint, dealing another blow to efforts to use a synthetic lethal mechanism to overcome resistance to immuno-oncology drugs.
The LATIFY trial enrolled patients with locally advanced or metastatic non-small cell lung cancer. Patients had progressed on or after prior anti-PD-(L)1 therapy and platinum-based chemotherapy. Half of the 594 patients received the ATR kinase inhibitor ceralasertib in combination with AstraZeneca’s PD-L1 drug Imfinzi. None of the patients had actionable genomic alterations.
AstraZeneca found overall survival was no better on the combination than standard-of-care docetaxel, causing the trial to miss its primary endpoint. The Big Pharma plans to share data at a medical meeting. For now, the only other available detail is that the combination was generally well tolerated.
Susan Galbraith, Ph.D., AstraZeneca’s executive vice president for oncology hematology R&D, discussed the setback in a statement. Galbraith said the goal was to “reinvigorate the immune response of patients with lung cancer whose tumors stopped responding to available therapies by combining ATR inhibition with immunotherapy.”
The executive added that AstraZeneca remains committed to “pioneering new medicines to address the urgent need to improve outcomes for patients with lung cancer.” However, Galbraith made no comment in her statement on AstraZeneca’s commitment to ceralasertib.
LATIFY is the only AstraZeneca-sponsored phase 3 ceralasertib trial, although AstraZeneca is continuing to track patients in phase 2 solid tumor trials of the drug. The only AstraZeneca-sponsored ceralasertib trials that are recruiting or preparing to recruit participants are phase 1 assessments of bioavailability and the ATR kinase inhibitor’s effect on other drugs.
The phase 3 flop is another blow to the ATR space. AstraZeneca stopped (PDF) a phase 2 study of ceralasertib in melanoma early for futility in 2023. Roche walked away from Repare Therapeutics’ ATR candidate months later, while Bayer and Germany's Merck KGaA have also suffered setbacks.