AstraZeneca broadens first-line immuno-oncology NSCLC development programme

AstraZeneca provided an update Tuesday on its late-stage immuno-oncology development programme in first-line non-small-cell lung cancer (NSCLC). The company stated that in addition to refining the endpoints of the MYSTIC trial, which is evaluating the benefit of durvalumab monotherapy and durvalumab plus tremelimumab combination therapy versus standard-of-care, it is also expanding the NEPTUNE trial with local patients to support the regulatory submission of durvalumab plus tremelimumab in China, and has initiated a new study dubbed PEARL of durvalumab monotherapy in Asia. 

In regards to the MYSTIC trial, which was originally designed to focus on progression-free survival (PFS), AstraZeneca said the study will now assess both PFS and overall survival (OS) endpoints in patients with PDL1-expressing tumours for both durvalumab monotherapy and the durvalumab plus tremelimumab combination, as well as in "all comers" for the combined therapy arm. According to the company, the change "is based on recent internal and external data, including durvalumab's strong efficacy in monotherapy presented at recent medical meetings, as well as significant opportunities in the competitive landscape." PFS data from MYSTIC are anticipated in mid-2017, with final OS results expected no later than 2018, the drugmaker added.

Meanwhile, AstraZeneca indicated that the expansion of the NEPTUNE trial will not delay the anticipated OS data readout in 2018 from the global cohort. The company also noted that the PEARL study will focus on Asian countries, mainly China, "due to the high prevalence of NSCLC in the region."

Chief medical officer Sean Bohen said "the MYSTIC trial amendments, the NEPTUNE trial expansion and initiation of the new PEARL trial are all designed to enhance our options" in first-line immunotherapy as a combination and as monotherapy. He added "we continue to follow the science through both internal and external sources for the benefit of patients and look forward to sharing our first pivotal data in mid-2017." 

Commenting on the news, Sanford C. Bernstein analyst Tim Anderson suggested some would view the expanded development programme as a move by AstraZeneca to enhance its chances of success, while others may claim the changes indicate it has less confidence in the combination approach. He also remarked that by obtaining information from additional subgroups in the studies, AstraZeneca may reduce the quality of the data included in the final analysis, adding the drugmaker "has decided to roll the dice on this matter for the sake of having results more quickly." 

The FDA previously awarded priority review and breakthrough therapy status to durvalumab for the treatment of certain patients with urothelial cancer. Meanwhile, Berenberg Bank analyst Alistair Campbell forecast combined peak sales of durvalumab and tremelimumab of approximately $5 billion annually.