GSK gets a lung cancer PARP delay

While GSK’s PARP inhibitor Zejula is still in play in lung cancer, this is a setting in which this mechanism has failed to make a mark, and now the company has disclosed that readout of the phase 3 Zeal trial has been delayed. Results are expected in the first half of this year, versus the second half of 2024 previously, GSK said during its fourth-quarter results on Wednesday. The trial tests Zejula plus Keytruda, versus Keytruda, in first-line NSCLC maintenance, with a primary outcome of progression-free survival in responders. The omens aren’t promising: Merck and AstraZeneca’s Lynparza, alongside Keytruda, failed in a similar setting in the Keylynk-006 and 008 studies. And other projects have largely underwhelmed in earlier-stage trials. Meanwhile, in Zejula’s phase 2 first-line Jasper study, ORR was 56% ORR among 16 PD-L1-high patients, but 20% among 20 PD-L1-low subjects. Zeal doesn’t appear to focus on PD-L1-high patients, but will analyse PFS and OS by PD-L1 status as secondary endpoints. The idea behind using PARP inhibitors in lung cancers stems from the fact that some NSCLC patients have homologous recombination deficiency that could be targeted by this drug class. GSK will be bucking the trend if it can show a result here, however.

PARP inhibitors in NSCLC

Notes: *investigator-sponsored study; **PARP7 inhibitor; SCCL=squamous cell carcinoma of the lung. Source: OncologyPipeline.