Roche chemo-immunotherapy combo meet NSCLC Phase III endpoint

Roche said it will submit the data of the open-label study, which enrolled 1.202 stage IV NSCLC patients, to the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) and file for global market approval of the combo as first-line palliative treatment in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Despite data concerning overall survival are expected in Q1/2018 earliest, the company suggested there was a promising trend regarding  this co-primary endpoint. Safety for the Tecentriq and Avastin plus chemotherapy appeared consistent with the known safety profile of the individual medicines, and Roche said it identified no new safety signals with the combination.

Full data will be presented at the European Society for Medical Oncology (ESMO) Immuno Oncology Congress in Geneva, Switzerland in December 2017.

“We are extremely encouraged by these results and will submit these data to health authorities globally with the goal of bringing a potential new standard of care for the initial treatment of lung cancer,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “In addition to first-line NSCLC, we are testing the ability of Tecentriq and Avastin to enhance the potential of the immune system to combat a broad range of other cancers.”

The primary analysis of the co-primary PFS endpoint in IMpower150 was assessed in two populations: all randomised people without an ALK or EGFR genetic mutation (intention-to-treat wild-type) and in a subgroup of people who had a specific biomarker (T-effector “Teff” gene signature expression). IMpower150 met its PFS co-primary endpoint per study protocol for both populations assessed.

Tecentriq targets PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors with the aim of activation of T cells.

Last week, German oncologists from Munich-based Klinikum rechts der Isar warned that targeting the PD1/PD-L1 axis in order to activate T cells might result in unexpected outcomes. In Nature (doi:10.1038/nature24649), the team of Jürgen Ruland reported that PD1 acted as a tumour suppressor in a mouse model mimicking the blood cancer T-cell non-Hodgkin lymphoma. In the model PD1 targeting resulted in cancer. Mechanistically, intact PD1 blocks signaling by the kinases AKT and PKC and activates expression of the tumour suppressor PTEN. The researchers recommended to re-investigate approved treatments in the light of the new findings