Ceralasertib-Imfinzi Misses Survival End Point in Lung Cancer Trial

Ceralasertib in combination with Imfinzi (durvalumab) did not meet the primary endpoint of overall survival (OS) in the phase 3 LATIFY trial versus standard-of-care docetaxel in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), according to a news release from AstraZeneca.

“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 Haematology R&D, AstraZeneca, said in the 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.”

The trial evaluated patients without actionable genomic alterations whose disease had progressed on or after prior immunotherapy and platinum-based chemotherapy.

The combination of ceralasertib and Imfinzi was generally well tolerated. The safety profile matched what is already known for each medicine when used on its own, and no new safety concerns were identified. These findings will be presented at an upcoming medical meeting.

What is the Study design of LATIFY?

LATIFY is a randomized, open-label, multi-center, global phase 3 trial evaluating ceralasertib plus Imfinzi in patients with locally advanced or metastatic non-small cell lung cancer without actionable genomic alterations. All patients enrolled in the study had disease progression on or after prior anti–PD-(L)1 therapy and platinum-based chemotherapy.

Patients were randomly assigned to receive either the investigational combination or standard chemotherapy. Those in the combination group received ceralasertib oral tablets at a dose of 240 milligrams twice daily for seven days, along with a fixed 1,500-milligram dose of Imfinzi on day eight of each treatment cycle. Treatment cycles were repeated every four weeks. Patients in the comparison group received docetaxel every three weeks. Treatment continued until disease progression, unacceptable side effects, withdrawal of consent or until another discontinuation criterion was met. The trial enrolled 594 patients from more than 20 countries.

What is Ceralasertib?

Ceralasertib is an oral medication that selectively targets ATR kinase, a protein that plays a key role in how cells respond to DNA damage and maintain survival. By blocking this pathway, ceralasertib may help weaken cancer cells. When used in combination with immunotherapy, ceralasertib is designed to affect the tumor microenvironment by shifting it from a suppressed immune state to a more active one.

What is Imfinzi?

Imfinzi is a monoclonal antibody immunotherapy that binds to the PD-L1 protein. By blocking PD-L1 from interacting with PD-1 and CD80, Imfinzi helps prevent tumors from shutting down immune responses, allowing the immune system to better recognize and respond to cancer.

In lung cancer, Imfinzi is a global standard of care based on improvements in overall survival for patients with unresectable stage 3 non-small cell lung cancer whose disease has not progressed after chemoradiotherapy. Imfinzi is also approved as a perioperative treatment when given with chemotherapy for resectable non-small cell lung cancer. In addition, it is approved in combination with a short course of Imjudo (tremelimumab) and chemotherapy for metastatic non-small cell lung cancer. Imfinzi is also approved for limited-stage small cell lung cancer in patients whose disease has not progressed after concurrent platinum-based chemoradiotherapy, as well as for extensive-stage small cell lung cancer when used with chemotherapy.

Reference

1. “Update on LATIFY Phase III trial of ceralasertib plus Imfinzi in previously treated advanced non-small cell lung cancer.” News Release. AstraZeneca.

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