A couple of weeks ago, Genentech announced that interim data were forthcoming (ESMO? SABCS seems a long way off) from IMpassion130, their P3, 900-subject, 1:1 randomized atezo + Abraxane v. placebo + Abraxane study in first-line, triple-negative metastatic breast cancer. To tide us over, they offered up a teaser: the study met its co-primary PFS endpoint in the intent-to-treat and PD-L1+ populations, and the company reported a positive trend in OS in the PD-L1+ population. The language was not subtle. In addition to touting 130 as the “first positive Phase III immunotherapy study in triple negative breast cancer,” Genentech said they were going to “submit to authorities globally with the aim of bringing this combination to people with triple negative breast cancer as soon as possible.”
What kind of data might be backing this up? Merck were slow to combine pembro and chemotherapy, so we don’t have a lot of context for what successful immunotherapy looks like in metastatic TNBC. But let’s mine abstract libraries past for details anyway. Continue reading “Handicapping IMpassion130”
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.
Continue reading “Galena and the vaccine that won’t die”
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.
Continue reading “Nivo disappoints, but it didn’t have to be this way”