Galena continues to hobble along with NeuVax, resisting defeat even though their peptide vaccine targeting HER2-positive breast cancer has failed in patients who have HER2-positive breast cancer as well as in patients who have breast cancer that is, ahem, HER2-lite (this is not a thing). With each failed study, Galena becomes less ambitious: the company announced the presentation of a study-update abstract at San Antonio where the study in question features neither real cancer nor real endpoints.
This is unpleasant: a paper published in Clinical Cancer Research described a pattern of “hyperprogression” identified in patients treated with PD-1/PD-L1 inhibitors in clinical trials at Gustave Roussy. The investigators compared tumor growth rate (TGR) prior to treatment with PD-1/PD-L1 agents with the TGR after, defining hyperprogression as greater than or equal to a two-fold increase of the TGR between the reference and post-treatment periods (and here I thought the worst thing that could happen was toxic epidermal necrolysis; see Google Images for more on that one). In the evaluable population of 131 patients, 9% met the definition of hyper-progressive disease, which was associated with older age and shorter OS.
While time to progression generally decreases with lines of treatment, a 2x+ increase in rate of growth seems particularly dramatic, and it’s another blemish on what was considered for a while a unicorn of cancer therapy. Continue reading ““Hyperprogression” identified as a risk of checkpoint inhibitors”
In August, when BMS announced that nivolumab failed to meet its primary endpoint in Checkmate 026, I brushed it off. The flaw was obvious: Checkmate 026 randomized treatment-naive advanced non-small cell lung cancer (NSCLC) subjects with PD-L1 of 1+% to nivo monotherapy or chemo. The competing Merck pembrolizumab study targeted the same previously untreated advanced NSCLC patient population, with the significant difference that Merck’s patients were enrolled based on 50+% PD-L1 expression (note: the studies used different diagnostics/PD-L1 thresholds).
So BMS over-reached. They went head-to-head with Merck for the broader label (not requiring positive PD-L1 expression for treatment, which dramatically increases the patient population), and hubris makes fools of us all. Like a lot of people, I figured the results would improve on subgroup analyses.
As you’ve seen by now, the results did not improve, and Checkmate 026 appears unsalvageable.