Cascadian Therapeutics (CASC)

[io_io]

Cancer Clinical Research Paper

"A Peptide Vaccine Strategy in NSCLC"

http://clincancerres.aacrjournals.org/cgi/reprint/13/15/4652s

It covers the PIIb data in brief. At the end, there is this -

Open Discussion

Dr. Thomas Lynch: How many of us are skeptical that immune therapy will ever pan out in non–small cell lung cancer? Show of hands. So we have a skeptical crowd. I would argue that this randomized phase II study was well done. It has been interpreted it in the right way. The data have not been oversold, as was done with other immune compounds in the past.

Dr. Bruce Johnson: I am skeptical. I hope I am wrong. We commonly see that a new immunological compound does not work in the whole group, it works in a subset. It may or may not have been a planned subset, and appropriately, this finding generates additional hypotheses. Then, when it is tested in that subset, historically, it does not work for the specific subgroup. It would be helpful to understand why this would work in stage IIIB and not in the other patients.

Dr. Butts: Some of the negative trials involved poor selection of patients. It takes at least 8 weeks just to deliver the vaccine. If you are doing that in patients with metastatic or refractory non–small cell lung cancer, you don't have time to show a difference. In terms of why it would work in stage III versus stage IV disease, immune resistance mechanisms are much more active in advanced disease. We have learned more about these mechanisms of immune resistance, and many of the vaccine strategies are trying to incorporate ways to get around them. Cyclophosphamide, for example, may inhibit suppressor T-cell function.

Dr. Angela Davies: While I am one of the skeptics, patients love these studies. The concept of stimulating your immune system is why they go to the naturopath, the Chinese herbal store, because they love that concept that they are fighting their cancer with their own immune system. Accrual is going to be very successful; whether it will work or not is another issue.

Dr. Butts: We had to do a phase II trial to demonstrate that that adjuvant did not produce undue toxicity. We did it in the stage III setting with five or six centers in Canada accruing 22 patients in about 6 months. I rarely have a patient say, "I'm not interested in the vaccine trial."

Dr. Johnson: If you get your chest, including the thymus, irradiated, that could be good, it could be bad, and it would be nice to have an explanation. Do you have some idea about whether irradiating a person's chest helps or hurts the vaccine?

Dr. Butts: We don't have any specific data. A number of these stage III patients did get radiation, and that is where we see the survival signal. There is some potential for an enhancement to the immune response because when you get tumor kill, you get release of new antigens and so there is antigen spreading within the immune system. So, if you stimulate response to MUC1, you may actually get cross-stimulation to other antigens that are released after you treat the tumor.