Planned HERIZON-GEA-01 Analyses and the Doublet-vs-Triplet Question

In this episode, Dr. Wainberg, Dr. Shah, and Dr. Elimova discuss planned HERIZON-GEA-01 analyses and consider how to weigh the doublet and triplet regimens. Dr. Elimova confirms that two additional event-driven analyses are planned: the next likely before the end of the year, with a subsequent final analysis. She notes that at the current cut, the zanidatamab-plus-chemotherapy doublet did not meet the pre-specified p-value for overall survival (OS), with a hazard ratio (HR) of 0.80 and P=0.0564, which she describes as a trend.

Dr. Shah raises a hypothetical: If the doublet later meets OS, the statistical analysis plan allows formal sequential comparison between arms B (doublet) and C (triplet). He suggests that the triplet may not be statistically superior to the doublet on OS, and he asks Dr. Elimova — in that hypothetical — how Canadian funding bodies might weigh tislelizumab in addition to zanidatamab plus chemotherapy.

Dr. Elimova shares her personal view that tislelizumab appears to contribute something, pointing to further separation of the triplet and doublet survival curves after the PFS window, which she interprets as an effect on long-term survivors. She notes that Health Canada approvals are usually not the bottleneck in her system; provincial funding through the pan-Canadian Pharmaceutical Alliance (pCPA) determines whether the marginal benefit justifies the marginal cost. She advocates for correlative work to characterize long-term survivors.

In the next episode, “Considering the Zanidatamab Triplet in the PD-L1 CPS <1 Patient,” the panel discusses how HERIZON-GEA-01 data inform treatment for patients with PD-L1 CPS <1 disease.