Abstract OT3-01-04: VADIS trial: Phase II trial of the nelipepimut-S peptide <u>v</u> <u>a</u>ccine in women with <u>D</u>C<u>IS</u> of the breast
Authors: EA Mittendorf, G Plitas, J Garber, K Crew, B Heckman-Stoddard, M Wojtowicz, L Vornik, GE Peoples, PH Brown
Journal: Cancer Research (2017)

Abstract Background: Our group has been investigating vaccination strategies in breast cancer. Specifically, we have been evaluating HER2-derived peptide vaccines including nelipepimut-S+GM-CSF administered adjuvantly to breast cancer patients who have been rendered disease-free with standard of care therapy but are at high risk for recurrence. Early phase clinical trials showed an approximately 50% reduction in relative recurrence risk in vaccinated patients. Based on these data, nelipepimut-S+GM-CSF is being evaluated in a phase III registration trial. Having shown the vaccine to be safe, effective in stimulating an antigen-specific immune response and potentially having clinical efficacy in the setting of secondary prevention, the current study was initiated to evaluate vaccination in DCIS patients. This trial represents an initial step to move the vaccine into the primary prevention setting. Trial Design: Phase II, randomized, single-blind study. Patients will be randomized 2:1 to receive vaccine or GM-CSF alone. After enrollment, patients will receive 3 inoculations administered every other week preoperatively followed by surgery then completion of the vaccination series (3 additional inoculations) in the adjuvant setting. Eligibility: The trial will enroll pre- or post-menopausal women with a diagnosis of DCIS made by core biopsy. The area of radiographic abnormality must measure at least 1 cm. Because the vaccine is a MHC class I, CD8+ T cell-eliciting vaccine, it is HLA restricted, and patients must be HLA-A2+ to enroll. Participants must also have an ECOG performance status &amp;lt;2, adequate cardiac, kidney and liver function and be willing to comply with all study interventions and follow-up procedures. Specific Aims: The trial's primary endpoint is to evaluate for nelipepimut-specific CD8+ T cells in the peripheral blood of vaccinated patients compared to patients receiving GM-CSF alone. Secondary endpoints include evaluating toxicity; determining the immune response in vivo by DTH, in vitro by evaluating for epitope spreading to other tumor antigens, and importantly in the tumor by assessing the degree of lymphocytic infiltration in surgically resected specimens. The extent of HER2 expression, Ki67 and cleaved caspase 3 in the resected specimen will also be assessed. Statistical Methods: A total of 108 DCIS patients will be consented and screened for eligibility. 48 (45%) are expected to be HLA-A2 positive. These 48 patienst will be randomized 2:1 to vaccine or GM-CSF alone groups. Accounting for 10% attrition rate and for an approximately 5% non-evaluable sample rate, we expect to have 40 evaluable patients, 27 in the vaccine group and 13 in the GM-CSF alone group, that have baseline, pre-surgery, and post-surgery measures of nelipepimut-S-specific CD8+ T cells. We will have 82% power to detect a significant increase in nelipepimut-S-specific CD8+ T cells in the vaccine group versus the GM-CSF alone group. Contact Info: The study is accruing at four sites to include Columbia University, Dana Farber Cancer Institute, MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center. Additional information can be obtained from the overall study PI, Dr. Elizabeth Mittendorf (eamitten@mdanderson.org). NCT0236582. Citation Format: Mittendorf EA, Plitas G, Garber J, Crew K, Heckman-Stoddard B, Wojtowicz M, Vornik L, Peoples GE, Brown PH. VADIS trial: Phase II trial of the nelipepimut-S peptide vaccine in women with DCIS of the breast [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-01-04.