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.
That’s right: the study population is DCIS patients, and the primary endpoint is the mere presence of “[NeuVax]-specific CD8+ T cells” in peripheral blood. (To be fair, you can’t use PFS as an endpoint in a study where patients don’t recur because they don’t have cancer, and they had to measure something.) Patients will be randomized to receive either NeuVax + granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM-CSF alone – that is, once the NCI allows them to start enrolling again (enrollment was suspended when the phase III failed so spectacularly; ClinicalTrials.gov shows the trial suspended at the time of this post, but the company says that hold has been lifted.)
Worth noting is that GM-CSF isn’t saline. It’s an immune stimulant. They give it to everyone during myleosuppressive chemotherapy to boost white blood cell counts, and it’s powerful enough that your bones throb after the injection because your bone marrow is working so hard. There is evidence that GM-CSF itself may have efficacy against cancer: this study found, in a very small group of patients, that the addition of GM-CSF to Herceptin stabilized disease progression in heavily pretreated metastatic patients for a median of 16 and up to 54 weeks. You could review those results and be inclined to enroll in the NeuVax study for the GM-CSF alone, which is the only reasonable excuse a patient would have to bother with this agent; however, that’s a terribly short-sighted choice, because among the manipulative tactics employed during study enrollment is failure to mention that immunotherapy studies almost always include a blanket exclusion regarding prior treatment with vaccines or immunotherapy. This is true with all the immunotherapy studies I’ve seen; no novel PD-1 combo study is going to take you if you’ve been treated previously with a different anti-PD-1 agent, for example. Chemo studies are usually more flexible, but with immune agents, current practice is that you get one shot.
Presumably, the latest plan for NeuVax is that the presence of these “NeuVax-specific” immune cells in DCIS patients will correlate to lack of progression to invasive disease. This is a company that once insisted that patients with lower levels of HER2-expression would respond better to a HER2-targeted therapy than patients with the highest levels of HER2-expression, so venturing only that “NeuVax-specific” T-cells may exist following treatment with NeuVax and not making any bizarre claims about what they may do (bold guess: nothing) seems to reflect a little more science than we’ve seen from Galena so far. But this isn’t a path to market. I can’t guess at how many patients and what kind of follow-up would be needed in later-stage trials to generate the statistical rigor that would win NeuVax any efficacy claims, nevermind the enrollment issues with a true randomized chemoprevention trial in DCIS (we still treat DCIS like it’s invasive cancer and don’t have a standard-of-care chemoprevention strategy to serve as a comparator). The industry has enough vaccine fatigue as it is, and wasting study subjects on this DOA agent is particularly egregious when there are waves of immmunotherapies to come and even some intriguing vaccines on the horizon. To that point, GP2 and NeuVax share a PI, which could just be a funny byproduct of upholding the principle of equipoise, but as a patient, it’s hard not to take a more cynical view. You get one chance at these treatments. Don’t use it on NeuVax.