Summit’s shot at early Harmoni backfires

Summit has tinkered extensively with Harmoni-3, the first-line lung cancer trial of its Akeso-partnered anti-PD-1 x VEGF project ivonescimab, but its latest amendment, implemented two months ago, just backfired. The change, introducing an interim PFS analysis in patients with the squamous histology, was designed to give Summit a shot at earlier FDA approval, but the interim analysis has drawn a blank, the group disclosed on Thursday. On the face of it this is no big deal, as Harmoni-3 continues unchanged towards final PFS analysis, and first interim OS analysis, in the second half; but the optics of the miss are poor, and Summit shares opened down 24% on Friday. One read is that the PFS benefit is borderline, and as a result Harmoni-3’s chances of hitting on the gold-standard endpoint of OS are remote. However, nothing is known about either the interim bar for PFS or by how much it’s been missed. Evercore ISI’s Cory Kasimov speculated that Summit powered the interim assuming that PFS would hit close to a 0.6 hazard ratio, and noted that the data-monitoring committee didn’t activate a safety-based futility analysis. Attention now turns to Harmoni-3’s Chinese equivalent, Harmoni-6, due to be presented at ASCO.