Ceralasertib Combo Misses OS End Point in Advanced NSCLC Trial

Combining ceralasertib with durvalumab (Imfinzi) did not reach the primary end point of overall survival (OS) compared with docetaxel among patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) in the phase 3 LATIFY trial (NCT05450692), according to a press release from the developer, AstraZeneca.¹

The experimental regimen was found to be well tolerated among patients; the safety profile was comparable with prior reports of each individual agent. Investigators plan to present detailed results from the LATIFY trial at a future medical meeting.

“Our goal in the LATIFY trial was to reinvigorate the immune response of patients with lung cancer whose tumors stopped responding to available therapies by combining ATR inhibition with immunotherapy,” Susan Galbraith, executive vice president, Oncology Hematology Research & Development at AstraZeneca, stated in the press release.¹ “While we are disappointed by this result, we remain committed to pioneering new medicines to address the urgent need to improve outcomes for patients with lung cancer through our industry-leading portfolio.”

Developers engineered ceralasertib as an orally available selective ATR kinase inhibitor. When sequenced with immunotherapy, the agent is designed to act on the tumor microenvironment by transferring it from a suppressed immune state to an activated state.

The open-label, multi-center, international phase 3 LATIFY trial assessed ceralasertib plus durvalumab among patients with locally advanced or metastatic NSCLC who lacked actionable genomic alterations and whose disease progressed on or after previous immunotherapy and platinum-based chemotherapy. A total of 594 patients across more than 20 countries were randomly assigned 1:1 to receive ceralasertib at 240 mg twice daily for 7 days plus durvalumab at 1500 mg on day 8 every 4 weeks or standard-of-care docetaxel every 3 weeks until progressive disease, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria were fulfilled.

The trial’s primary end point was OS. Secondary end points included progression-free survival, objective response rate, duration of response, time to response, disease control rate, time to second progression or death, 12-month OS, time to deterioration of health-related quality of life, and adverse effects.²

Patients 18 years and older with histologically or cytologically confirmed NSCLC that is locally advanced or metastatic per Version 8 of International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology were eligible for enrollment on the trial. Other eligibility criteria included having documented radiological progressive disease on or after receipt of the most recent line of treatment, eligibility for second- or third-line treatment, an ECOG performance status of 0 or 1, adequate organ function and marrow reserve, a minimum life expectancy of 12 weeks, a body weight of more than 30 kg, and no cancer-related cachexia.

Those with mixed small cell lung cancer and NSCLC histology, another primary malignancy apart from a disease treated with curative intent with no known active disease more than 5 years before beginning study treatment, or persistent toxicities associated with prior anticancer treatment were ineligible for enrollment on the trial. Patients were also unable to enroll if they had active or previously documented autoimmune or inflammatory disorders, more than 1 line of prior anti–PD-(L)1 therapy, more than 1 prior line of platinum-based chemotherapy in the metastatic setting, or prior receipt of an ATR inhibitor. Additionally, patients must not have experienced a toxicity resulting in permanent discontinuation of a prior anti–PD-(L)1 agent, and all toxicities associated with prior anti–PD-(L)1 treatment must have completely resolved.

References

1. Update on LATIFY Phase III trial of ceralasertib plus Imfinzi in previously treated advanced non-small cell lung cancer. News release. AstraZeneca. December 22, 2025. Accessed December 22, 2025. https://tinyurl.com/3c6bu7s6
2. A phase III study of ceralasertib plus durvalumab versus docetaxel in patients with non small cell lung cancer (NSCLC) whose disease progressed on or after prior anti PD (L)1 therapy and platinum based chemotherapy (LATIFY). ClinicalTrials.gov. Updated November 19, 2025. Accessed December 22, 2025. https://tinyurl.com/33r4kmfz