As reported on PharmaBiz, AstraZeneca’s phase III LATIFY trial has fallen short of its primary objective, with the combination of the ATR inhibitor ceralasertib and the PD‑L1 inhibitor Imfinzi (durvalumab) failing to improve overall survival compared with docetaxel in patients with advanced non‑small cell lung cancer (NSCLC) previously treated with immunotherapy and platinum chemotherapy.
Study Overview and Findings
LATIFY enrolled 594 patients across more than 20 countries, focusing on individuals with locally advanced or metastatic NSCLC lacking actionable genomic alterations. All participants had experienced disease progression after prior PD‑(L)1–based therapy and platinum‑based chemotherapy. Patients received either ceralasertib plus Imfinzi on a four‑week cycle or standard docetaxel every three weeks.
The investigational combination did not demonstrate a survival advantage, the study’s main endpoint. Secondary measures—including progression‑free survival, objective response rate, and patient‑reported outcomes—will be detailed at an upcoming medical conference.
Despite the efficacy miss, the combination’s safety profile aligned with existing data for the two agents, and no new toxicity signals were observed.
AstraZeneca’s Perspective
Susan Galbraith, AstraZeneca’s executive vice president of oncology R&D, noted that the trial was designed to restore antitumor immune activity in patients whose cancers had become resistant to prior treatments. She acknowledged the disappointment but reaffirmed the company’s commitment to developing novel therapeutic strategies for lung cancer, an area with significant unmet need.
Background on the Therapeutics
Ceralasertib is an oral, selective ATR kinase inhibitor intended to disrupt tumor DNA‑damage responses and enhance immune activation, particularly when paired with immunotherapy. Imfinzi, a widely used PD‑L1 inhibitor, plays a central role in the treatment of several lung cancer settings, including unresectable stage III NSCLC, resectable disease in the perioperative context, and both limited‑ and extensive‑stage small cell lung cancer. It is also approved across multiple gastrointestinal, hepatobiliary, gynecologic, and urologic malignancies.
More than 414,000 patients worldwide have been treated with Imfinzi since its initial approval in 2017, and the drug remains central to AstraZeneca’s broad immuno‑oncology development program.
AstraZeneca’s Broader IO Strategy
While LATIFY did not achieve its intended outcome, AstraZeneca continues to invest heavily in immune‑based oncology research. The company is exploring next‑generation approaches—including bispecific antibodies, T‑cell‑engaging therapies, and strategies to overcome treatment resistance—with the long‑term objective of extending durable survival benefits to more patients and moving effective immunotherapies into earlier disease stages.
