On March 18, 2020 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported preliminary antigen-specific immune response data from a Phase 2 randomized investigator-sponsored trial (IST) of nelipepimut-S (NPS) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in women with ductal carcinoma in situ (DCIS) of the breast who are HLA-A2+ or A3+ positive, express HER2 at IHC 1+, 2+, or 3+ levels, and are pre- or post-menopausal (Press release, Sellas Life Sciences, MAR 18, 2020, View Source [SID1234555668]).
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"We are pleased to report preliminary results from the National Cancer Institute-sponsored Phase 2 VADIS trial, showing NPS is capable of inducing an antigen-specific antitumor immune response in DCIS patients even after a single vaccination, which is particularly encouraging," said Angelos M. Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "Based on the immunobiological mechanism of action of NPS, we believe that NPS could be synergistic with standard therapies or novel immunotherapeutic approaches in women with DCIS. Moreover, these data correlate to previous findings of NPS in patients with invasive (non-DCIS) breast cancer. Given NPS’ low toxicity burden and high antigen-specific immune response, further clinical study of NPS as a therapeutic which could address the medical need of women with DCIS at an early stage of their therapeutic journey is likely warranted and these data further support our business development efforts to seek out-licensing opportunities to fund and conduct the future clinical development of NPS in order to maximize the potential of the program."
The study enrolled 13 patients, with nine patients receiving NPS plus GM-CSF and four patients receiving GM-CSF only. The relative frequency of NPS-specific CD8 cytotoxic T-lymphocytes as a percentage (NPS-CLT%) was twice as large in the NPS-treated patients. The NPS-CLT% was measured in the peripheral blood by a sensitive and specific assay using dextramer staining followed by flow cytometry, both at baseline (before vaccination or GM-CSF) and at 30 (+/-7) days after surgery. The mean difference in NPS-CTL% increase between the active and control groups was +0.10% vs +0.05%. The relative magnitude of change in NPS-CTL% mean values in NPS-treated patients over time was an 11-fold increase, from 0.01% at baseline to 0.11% after surgery, indicating a continued antigen-specific T-cell response post-NPS vaccination. NPS was generally well-tolerated in the study with no drug-related unexpected serious adverse reactions. The overall adverse event profile was consistent with previous safety data.
The final data is being further analyzed by the National Institute of Health, MD Anderson Cancer Center and the study principal investigator, Dr. Elizabeth Mittendorf, MD, PhD of the Dana-Farber/Brigham and Women’s Cancer Center, and will be presented at an upcoming medical conference.
"The preliminary data from the VADIS study showing a doubling of the difference in increase in antigen-specific CD8 cytotoxic T-lymphocytes in NPS-treated patients vs. controls, even with a single NPS inoculation, indicate in vivo immunogenicity of this cancer vaccine in DCIS. These data, as well as the previously reported clinical effects of NPS in the adjuvant setting after frontline therapy for invasive breast cancer, provide support for the possibility that NPS may be able to decrease the rate of recurrences in earlier-stage disease, such as DCIS, which I believe should be studied formally in future clinical studies," said Dr. Mittendorf. "While additional analyses of certain histologic and molecular markers of the patients’ immune responses against the NPS and other HER2 antigenic epitopes are currently ongoing, these initial immunobiological results from the VADIS study are encouraging."
About the Phase 2 VADIS Trial
This Phase 2 randomized trial is sponsored and operationalized by the National Cancer Institute (NCI) to study NPS’ potential clinical effects in earlier-stage disease. Patients are randomized to receive, prior to surgery, either GM-CSF followed by NPS two weeks later or GM-CSF alone. The primary endpoint of the trial is the difference in the frequency of newly induced NPS-cytotoxic T lymphocytes (CTL; CD8+ T-cell) in peripheral blood between the two arms of the study, using a dextramer assay. Secondary endpoints to be compared between the two arms include the nature and incidence of adverse events and in vivo immune response to NPS, in addition to other select histologic and molecular biomarkers.
About DCIS
DCIS is defined by the NCI as a noninvasive condition in which abnormal cells are found in the lining of a breast duct and have not spread outside the duct to other tissues in the breast. DCIS is the most common type of breast neoplasm with malignant potential. In some cases, DCIS may become invasive cancer and spread to other tissues and, currently, it is not possible to know which lesions could become invasive. Current treatment options for DCIS include breast-conserving surgery and radiation therapy with or without tamoxifen, breast-conserving surgery without radiation therapy, or total mastectomy with or without tamoxifen. Tamoxifen is given in cases with hormone receptor positivity only. No targeted or immune therapies have shown any definitive clinical activity in DCIS to date. The current standard treatment aims at forestalling the progression of DCIS to invasive cancer. In approximately 15-25% of cases progression does occur. DCIS is diagnosed in more than 60,000 women each year in the United States, comprising 1 in 5 newly diagnosed cases of breast cancer.