AstraZeneca’s Lung Cancer Trial Fails to Meet Primary Endpoint – What’s Next?

AstraZeneca (AZN) shares are facing scrutiny following the announcement that its Phase III LATIFY trial, evaluating ceralasertib in combination with Imfinzi (durvalumab), did not meet its primary endpoint of overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC).

The trial focused on patients without actionable genomic alterations (AGAs) whose disease had progressed after prior immunotherapy and platinum-based chemotherapy.

The failure of the LATIFY trial represents a setback for AstraZeneca's immuno-oncology pipeline, specifically its efforts to enhance the effectiveness of Imfinzi in later-stage NSCLC.

While the combination therapy was generally well-tolerated, the inability to demonstrate a statistically significant improvement in overall survival compared to standard-of-care docetaxel raises questions about the future of ceralasertib in this treatment setting.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, expressed disappointment, stating the company remains committed to pioneering new medicines for lung cancer.

The complete data from the LATIFY trial will be presented at an upcoming medical meeting, which may offer further insights into the trial's outcome and potential future research directions.

The NSCLC market is a significant area of focus for pharmaceutical companies, given that lung cancer is a leading cause of cancer death.

Approximately 80-85% of lung cancer cases are NSCLC, and the prognosis for patients with metastatic disease remains poor, with only about 12% surviving five years after diagnosis. This unmet need drives ongoing research and development efforts, but the LATIFY results underscore the challenges in improving outcomes in this patient population.

The LATIFY trial targeted a specific subset of NSCLC patients who had already progressed on prior immunotherapy and chemotherapy, a population known to be difficult to treat. Ceralasertib is an ATR kinase inhibitor designed to enhance the immune response in combination with immunotherapy.

The trial's failure suggests the hypothesized synergy with Imfinzi did not translate into improved survival outcomes in this setting. The trial's comparator arm, docetaxel, remains a standard chemotherapy option for advanced NSCLC, highlighting the difficulty in surpassing existing treatments.

It was also announced on Monday that AstraZeneca and Daiichi Sankyo's Enhertu has been granted Breakthrough Therapy Designation (BTD) in the US “for adult patients with HER2-positive early breast cancer with residual invasive disease in the breast and/or axillary lymph nodes after neoadjuvant treatment and high risk of disease recurrence.”

The Food and Drug Administration (FDA) BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need.