Breast Cancer
RANDOMIZED, BLINDED, CONTROLLED INVESTIGATOR-SPONSORED TRIAL (IST) WITH NPS IN COMBINATION WITH TRASTUZUMAB (HERCEPTIN®; GENENTECH/ROCHE) VS. TRASTUZUMAB ALONE IN HER2 1+/2+ BREAST CANCER PATIENTS.
This Phase 2b clinical trial is a randomized, multicenter, investigator-sponsored, 275 patient study which enrolled HER2 1+ and 2+, including triple-negative breast cancer (TNBC) patients, HLA A2+, A3+, A24 and/or A26, node positive, and high-risk node negative breast cancer patients. Eligible patients were randomized to receive NPS + GM-CSF + trastuzumab or trastuzumab + GM-CSF alone. (ClinicalTrials.gov Identifier: NCT01570036). Based on the final analysis of the full data-set from the clinical trial, and with a median follow-up of 25.7 months, no safety-related statistically significant differences were seen between the treatment and control arms in the rate of grade 1-3 adverse events of either local or systemic nature, while no grade 4/5 toxicities were observed in either arm. Also, there was no statistically significant difference between the treatment arms in the cardiac ejection fraction measured at baseline, as well as at four additional time-points up to 24 months post-randomization. In the intent-to-treat (ITT) population, the disease-free survival (DFS) landmark rate at 24 months was in favor of the combination (NPS plus trastuzumab) arm (89.8%) versus trastuzumab alone (83.8%) with a hazard ratio of 0.62 (P=0.18). In the 97-patient TNBC cohort, the DFS landmark rate at 24 months for patients treated with NPS plus trastuzumab was 92.6% compared to 70.2% for those treated with trastuzumab alone, a clinically and statistically significant improvement with a hazard ratio of 0.26 (P=0.01). In the TNBC cohort, there was a statistically significant reduction of 71.9% (P=0.01) in the frequency of clinically detected recurrences in those patients treated with the combination (NPS plus trastuzumab) versus trastuzumab alone (Hickerson A, et al. J Clin Oncol. 2019;37[Suppl 8], Abstr. 1). This IST was a clinical collaboration between SELLAS, Genentech/Roche, and the Henry M. Jackson Foundation.
FULLY ENROLLED, ONGOING RANDOMIZED, BLINDED, CONTROLLED IST WITH NPS IN COMBINATION WITH TRASTUZUMAB (HERCEPTIN®; GENENTECH/ROCHE) VS. TRASTUZUMAB ALONE IN HER2-POSITIVE (HER2 IHC3+) PATIENTS.
This multi-center, prospective, randomized, single-blinded Phase 2 trial has enrolled 100 patients with a diagnosis of HER2-positive (HER2 IHC3+) breast cancer who were HLA A2+ or HLA A3+ and determined to be at high-risk for recurrence. High-risk is defined as having received neoadjuvant therapy with an approved regimen that includes trastuzumab but not obtaining a pathological complete response at surgery, or those who undergo surgery as a first intervention and are found to be pathologically node-positive. Eligible patients were randomized to receive NPS + GM-CSF plus trastuzumab or GM-CSF plus trastuzumab alone. The primary endpoint of the study is disease-free survival (ClinicalTrials.gov Identifier: NCT02297698). Funding for this trial was awarded through the Congressionally Directed Medical Research Program (CDMRP), funded through the Department of Defense (DoD), via a Breast Cancer Research Program (BCRP) Breakthrough Award.
FULLY ENROLLED ONGOING RANDOMIZED, BLINDED, CONTROLLED IST WITH NPS PLUS GM-CSF VS. GM-CSF ALONE IN PATIENTS WITH DUCTAL CARCINOMA IN SITU (DCIS), ENTITLED: VADIS: PHASE 2 TRIAL OF THE NELIPEPIMUT-S PEPTIDE VACCINE IN WOMEN WITH DCIS OF THE BREAST.
VADIS is a randomized Phase 2 investigator-sponsored trial to evaluate women diagnosed with DCIS who are HLA-A2 positive, who express HER2 at IHC 1+, 2+, or 3+ levels, and who are pre or post menopausal. Patients were randomized to one of two arms: NPS plus GM-CSF or GM-CSF alone. The primary endpoint is immunologic and will evaluate the effect of the NPS on NPS -specific cytotoxic T lymphocytes to determine whether long-lasting immunity is induced (ClinicalTrials.gov Identifier: NCT02636582). DCIS is a noninvasive cancer in which abnormal cells are found in the lining of the breast duct and have not spread outside the milk duct to invade other parts of the breast. DCIS is the most common type of breast cancer, and in some cases, DCIS may become invasive cancer and spread to other tissues; currently it is extremely challenging to identify which lesions may convert to invasive cancer. This trial is being run in collaboration with the National Cancer Institute (NCI) Division of Cancer Prevention. The University of Texas-M.D. Anderson Cancer Center (MDACC) Phase I and II Chemoprevention Consortium is the lead for this multi-center trial. Preliminary antigen-specific immune response data from this Phase 2 IST showed that the relative frequency of NPS-specific CD8 cytotoxic T-lymphocytes as a percentage (NPS-CLT%) was twice as large in the NPS-treated patients, and the relative magnitude of change in NPS-CTL% mean values in NPS-treated patients over time was an 11-fold increase.