Do I think they’ll become standard therapy? I can only speak for the PRESENT trial that is enrolling patients who are HER2 1+, 2+ node positive, and they have the appropriate HLA haplotype. They have to be HLA-A2 or -A3 positive. If the results of this study were positive, then my hope is that it would lead to an application to the FDA for approval of nelipepimut-S in that clinical setting. I also think that it would open the door for investigation of other vaccines that can target the patients who don’t meet those criteria that I just mentioned, which are the eligibility criteria for PRESENT (perhaps they have a different HLA type, or perhaps they are HER2 3+, or other considerations).
Our group at MD Anderson is about to launch a trial with collaborators at Memorial Sloan Kettering, Dana Farber, and Columbia looking at the simple nelipepimut-S peptide vaccine strategy in DCIS.
r. Mittendorf: That’s a specific question that actually can have a really broad response. With the nelipepimut-S vaccine strategy specif- ically, it’s a single epitope. It stimulates CD8+T cells that recognize that epitope, but we’ve also shown that it causes something called epitope spreading. That means that it also stimulates T cells to recog- nize other epitopes. This response may be enough to prevent disease recurrence when administered in the adjuvant setting to patients who have been rendered disease-free with standard-of-care therapy
With that said, I think the PRESENT trial was designed in such a way that we’ve chosen the optimal patient population, the optimal dose, and an achievable hazard ratio. So do I think it will show a 70% reduction in recurrence, which is what we saw with the optimally dosed patients in the early phase trials? I think that is unlikely, but the study is not powered to show that. It’s powered to show a lesser but still very clinically relevant benefit. We’re hoping that that will be the case so that the vaccine would be offered to patients to whom it might be of benefit
Let's not minimize the non-futile result. It's important. Consequential. Transformative.
Galena (and future partners) have done the math -i.e. the statistical analyses. Trigger is 70th event/non-futile PR.
After Dr Fujii's latest update on S.Alpha, I really believe that non-futility will support the theory of achieving primary end-point.
go to this: breastcancertrials.o r g
Type in breast cancer vaccine or breast cancer immunotherapy.
Then, see how much clinical development is being done in this field. None are as advanced as Neuvax, PRESENT trial.
A good reference vs. listening to some idiots on this board or Fartstein and his buddies.
Oncology Clinical Trials: Successful Design, Conduct and Analysis
publié par Susan Halabi, PhD,Wm. Kevin Kelly.
Agree. Absolutely. One PR. Late June. If other PR before then, it will be related to other vaccine, interim phase II neuvax combo study, or partnership, of course. Otherwise, late June.
Means that the Independent data committee recommends to go forward with the trial as according to their statistical projections, study will meet primary end point.
Let's not minimize this outcome. Huge.
Also, despite the fact that the study has no stoppage rules at the interim point, the committee may recommend a halt for efficacy, especially if overall survival is skewed, and/or if the recurrence rate is extremely skewed in favour of neuvax. BUT, decision is to be taken by GALE only. That's when I would expect them to meet with FDA and discuss future plan of action.
Interesting. Somewhat strange that if 70th event to occur end of March, assessed by the central evaluating committee, say in April, data rolled up to independent committee in May, one day meeting, recommendation to GALE late May.....and only announced late June? Not sure what to make of it, but looks like a great sign to me
Trastuzumab increases uptake and cross-presentation of HER2-derived antigens by dendritic cells
Presentation Time: Sunday, Apr 17, 2016, 1:00 PM - 5:00 PM
Abstract Number: CT073
Presentation Title: Comparing an attenuated booster (E39’) vs E39 booster to potentiate the clinical benefit of the folate binding protein (FBP)-derived vaccine (E39 + GM-CSF) in a phase I/IIa trial to prevent recurrence in endometrial (EC) and ovarian cancer (OC) patients
Presentation Time: Tuesday, Apr 19, 2016, 8:00 AM -12:00 PM
Secondary prevention is the NEUVAX, PRESENT, phase III trial.
Dr. Mittendorf is the super-key investigator. Says tons of how well it will work.
March 15, 2016 | MBCC 2016, Breast Cancer
By Elizabeth A. Mittendorf, MD, PhD
Cancer Network: How has being both a surgeon and immunologist, shaped your views of the potential clinical roles of cancer vaccines?
Dr. Mittendorf: As a surgeon, I see and treat patients with early-stage breast cancer that is potentially curable. Unfortunately, despite our best treatment—surgery, chemotherapy when indicated, radiation if required—we still see recurrences in up to 20% of these patients. I think it is not unreasonable to hypothesize that this recurrence is in part attributable to a failure of the immune response against the cancer—hence my enthusiasm for vaccines that could potentially augment that antitumor immunity, thereby decreasing the risk of recurrence.
Cancer Network: In what settings do breast cancer vaccines show the most promise?
Dr. Mittendorf: Secondary prevention. There is currently one vaccine that is being investigated in a phase III trial—NeuVax—which is made up of an immunogenic peptide combined with an immunoadjuvant. The trial is vaccinating patients in the adjuvant setting with the goal being to determine if vaccination can decrease the risk of recurrence.