Ceralasertib plus durvalumab did not improve overall survival vs docetaxel in previously treated advanced non–small cell lung cancer.
Treatment with the combination of ceralasertib (AZD6738) and durvalumab (Imfinzi) did not improved overall survival (OS) vs docetaxel in patients with advanced non–small cell lung cancer (NSCLC) without actionable genomic mutations who experienced disease progression on prior immunotherapy and platinum-based chemotherapy, missing the primary end point of the phase 3 LATIFY trial (NCT05450692).1
Data from the study showed the combination regimen was generally well tolerated, with ceralasertib plus durvalumab displaying a safety profile consistent with the known toxicities of each agent.
Findings from LATIFY will be shared 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 of Oncology Hematology R&D at AstraZeneca, stated in a news release. “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.”
LATIFY was an open-label, randomized, multicenter study that enrolled patients at least 18 years of age with histologically or cytologically confirmed locally advanced or metastatic NSCLC.2 Patients needed to have EGFR and ALK wild-type disease. Disease progression following the most recent treatment regimen was required, and patients eligible for second- or third-line therapy needed to have received prior treatment with anti–PD-(L)1 therapy and platinum doublet chemotherapy, either in combination or sequentially.
Other key inclusion criteria comprised an ECOG or World Health Organization performance status of 0 or 1; adequate organ function and bone marrow reserve; and a life expectancy of at least 12 weeks.
Mixed NSCLC and small cell lung cancer histology precluded patients from enrollment. Patients were also excluded if they received more than 1 prior line of anti–PD-(L)1 therapy; experienced toxicity that led to permanent discontinuation of prior anti–PD-(L)1 therapy; experienced grade 3 or higher immune-mediated adverse effects (AEs) or any-grade immune-related neurologic or ocular AEs during prior treatment with immunotherapy; required immunosuppression beyond corticosteroids for AE management; experienced a recurrence of an AE when rechallenged; or were receiving maintenance doses of prednisone or equivalent agents at more than 10 mg per day. More than 1 prior line of platinum-based chemotherapy in the metastatic setting was also not allowed, and any prior treatment with an ATR inhibitor was not permitted.
Patients were randomly assigned 1:1 to receive oral ceralasertib at 240 mg twice per day for 7 days in combination with durvalumab at 1500 mg on day 8 of every 4-week cycle; or docetaxel once every 3 weeks.1 Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion was met. The study included 594 patients enrolled across more than 20 countries.
Along with the primary end point of OS, secondary end points comprised progression-free survival, objective response rate, duration of response, time to response, disease control rate, time to second progression, 12-month landmark OS, time to deterioration of health-related quality of life, time to deterioration of physical function, safety, and pharmacokinetics.2
