AstraZeneca’s PACIFIC-2 Phase 3 trial for Imfinzi in NSCLC falls short of primary endpoint

In the latest development in oncology research, AstraZeneca’s PACIFIC-2 Phase III trial, involving Imfinzi (durvalumab) concurrently administered with platinum-based chemoradiotherapy (CRT), did not achieve statistical significance for its primary endpoint of progression-free survival (PFS) in treating patients with unresectable, Stage III non-small cell lung cancer (NSCLC).

Imfinzi’s Established Role and PACIFIC-2’s Goals

Despite this outcome, Imfinzi, when sequentially administered after CRT, continues to be the global standard of care for unresectable, Stage III NSCLC, as established by the original PACIFIC Phase III trial. The PACIFIC-2 trial aimed to explore the potential benefits of concurrent administration of Imfinzi with CRT, particularly for patients who progress or are unable to continue CRT, thereby ineligible for the PACIFIC regimen.

Safety and Tolerability Insights

The initial analysis indicated that the safety and tolerability profile of Imfinzi and CRT in this patient population were consistent with known treatment profiles. However, an increased rate of infection was observed in the experimental arm during the concurrent treatment period.

AstraZeneca Continues Lung Cancer Research Despite PACIFIC-2 Trial Setback. Photo courtesy of D Wells/Wikimedia Commons.

Expert Perspectives on the Trial Results

Jeffrey D. Bradley, MD, the principal investigator of the trial, emphasized the importance of learning from these results to further cancer research. Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, reiterated the company’s commitment to expanding the benefit of immunotherapy in lung cancer treatments across various settings.

Future Directions in Lung Cancer Research

AstraZeneca continues to focus on several ongoing registrational trials testing Imfinzi in different stages of lung cancer, including in both resectable and unresectable NSCLC and small-cell lung cancer (SCLC). Imfinzi, as a human monoclonal antibody, plays a crucial role in countering tumor immune-evasion by binding to the PD-L1 protein and blocking its interaction with PD-1 and CD80 proteins.