Enhertu targets HER2-positive lung again

Over five years after first mooting the possibility, Daiichi Sankyo is taking Enhertu into a pivotal trial in first-line, HER2-positive lung cancer. This Destiny-Lung06 study, just unveiled in a clinicaltrials.gov listing, will pit a Keytruda combo against Keytruda plus chemo, in first-line NSCLC expressing HER2 (patients also can't express PD-L1 at 50% or higher). That's a subtly different setting from Enhertu's approved use in second-line NSCLC that's driven by mutated HER2, and where the front-line AstraZeneca-sponsored Destiny-Lung04 trial could serve as the confirmatory study. Readout of Destiny-Lung04, where Enhertu monotherapy is going up against Keytruda plus chemo, is an important second-half catalyst. Meanwhile, HER2-expressing NSCLC settings have taken something of a back seat since December 2019 (shortly after Daiichi licensed Enhertu to Astra), when the Japanese group's R&D day disclosed plans to start phase 3 studies in the second line, in stage III disease, and in the front-line setting. Within three years these studies had disappeared from Enhertu's development plan, and until the disclosure of Destiny-Lung06, which is scheduled to start in September, they were assumed to have been abandoned.

Selected trials of Enhertu in NSCLC

Note: *all phase 3 except 01 and 02. Source: OncologyPipeline.