Ceralasertib

AstraZeneca’s ceralasertib\'s phase 3 flop is another blow to the ATR space.\n 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.

AstraZeneca is spending $100 million upfront to secure ex-China rights for an early-stage cancer drug developed by Jacobio Pharma. The UK drugmaker will be responsible for advancing and selling the oral pan-KRAS inhibitor, JAB-23E73, in all markets except China, where it will co-develop and co-commercialize with Jacobio. The Beijing-headquartered biotech could get up to $1.9 billion in milestones, plus tiered royalties on future sales outside China, according to a Sunday release . KRAS is one of the “most important oncogenes in cancer,” AstraZeneca’s head of early oncology and precision medicine Matt Hellmann said in the release. KRAS mutations play a role in a variety of tumor types, including pancreatic, colorectal and lung cancers, he added. JAB-23E73 is currently in Phase 1 development in both the US and China, where it has shown “early signs of anti-tumor activity,” according to Jacobio. In China, the company is currently enrolling 334 patients with advanced solid tumors with a KRAS mutation in an open-label dose-escalation and dose-expansion Phase 1/2a trial. Data could come next year. In the US, the company is signing up 294 patients with tumors, including colorectal cancer, pancreatic ductal adenocarcinoma, and non-small cell lung cancer (NSCLC), for a similar trial that might report in 2027. The biotech developed the pill using its so-called Induced Allosteric Drug Discovery Platform, which uses computational and screening methods to pinpoint small molecules that can modify proteins. Jacobio’s oncology efforts have caught the attention of several drugmakers. In August last year, Shanghai Allist Pharmaceuticals licensed the China rights for a KRAS G12C inhibitor and an SHP2 inhibitor from Jacobio. In 2020, AbbVie licensed a suite of SHP2 inhibitors from the biotech, though it returned them a few years later. Not all of AstraZeneca’s recent developments in cancer have been positive. On Monday, the pharma admitte d that a Phase 3 trial of Imfinzi in combination with the ATR kinase inhibitor ceralasertib had failed. The Imfinzi regimen didn’t significantly improve overall survival over the standard of care docetaxel in patients with locally advanced or metastatic non-small cell lung cancer. The company said it would share detailed results from the study, called LATIFY, at a future medical meeting.