On February 14, 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 feedback from a Type C review with the U.S. Food and Drug Administration (FDA) regarding its clinical development program for nelipepimut-S (NPS) in patients with triple negative breast cancer (TNBC) (Press release, Sellas Life Sciences, FEB 14, 2020, View Source [SID1234554363]). Based on written feedback from the FDA and on the totality of clinical, safety and translational NPS data presented to date, the Company has finalized the design and plan for a Phase 3 registration-enabling study of NPS in combination with trastuzumab for the treatment of patients with TNBC in the adjuvant setting after standard treatment. If successful, this study may be considered as the basis for a Biologics License Application (BLA) submission to the FDA.
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"We are indeed pleased with the feedback and final outcome from our discussions with the Agency, after extended interaction with them, on the optimal and mutually acceptable design of a potential registration-enabling Phase 3 clinical trial for NPS in combination with trastuzumab. Importantly, we believe we have established an appropriate and expedient pathway to potentially bring NPS in combination with trastuzumab to patients in need as quickly as possible," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "We believe this regulatory clarity will enhance 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 as we continue to focus all of our resources on the development of our lead asset, galinpepimut-S, which recently entered a registrational Phase 3 study in acute myeloid leukemia."
The planned Phase 3 study will be a 1:1 randomized, blinded two-arm study to evaluate the efficacy and safety of the NPS vaccine (NPS plus granulocyte macrophage-colony stimulating factor (GM-CSF)) in combination with trastuzumab vs. GM-CSF alone as maintenance treatment in the adjuvant setting following standard-of-care therapy in patients with TNBC, defined as hormone receptor-negative, HER2 1+/2+ tumors (as assessed by immunohistochemistry tumors), at high risk of recurrence. The FDA indicated in its feedback that there is adequate safety information to support the use of NPS in combination with trastuzumab.
SELLAS previously reported the final efficacy and safety results from a Phase 2b study of NPS in combination with trastuzumab in TNBC patients (n=97). The disease-free survival (DFS) rate at 24 months was 92.6% for the combination arm vs. 70.2% for the trastuzumab alone arm, a clinically meaningful and statistically significant improvement in favor of the combination therapy (p=0.01). This was associated with a statistically significant reduction of 71.9% (p=0.01) in the frequency of clinically detected recurrences also in favor of the combination arm. Immune response analysis showed that non-recurrent TNBC patients mounted both vigorous NPS-specific clonal CD8+ cytotoxic T-lymphocyte expansion and enhanced in vivo post-antigen challenge cutaneous delayed type hypersensitivity. Most treatment-emergent adverse events were mild or moderate and consisted of manageable local injection site reactions, skin induration, pruritus, and fatigue.
"TNBC is an aggressive type of breast cancer with limited treatment options and poor prognosis, as it is associated with high levels of refractoriness and relapse not only in the metastatic setting, which is true for all types of breast cancer, but also at an early stage. Indeed, following standard frontline chemotherapy, TNBC can relapse as early as within 1−3 years, often with a pattern including visceral metastases. Therefore, optimizing relapse-mitigating approaches in women with TNBC following initial standard therapy (surgery + radiotherapy + chemotherapy) with further safe and effective adjuvant therapy is paramount," said Elizabeth A. Mittendorf, MD, PhD, Rob and Karen Hale Distinguished Chair in Surgical Oncology, Director of Research, Breast Surgical Oncology Brigham and Women’s Hospital, Director, Breast Immuno-Oncology Program Dana-Farber/Brigham and Women’s Cancer Center, and the Principal Investigator of this planned Phase 3 study. "A Phase 3 study investigating the potential clinical benefit accorded by NPS with trastuzumab, an easily-administered maintenance therapy with a generally manageable toxicity profile, has the potential, assuming positive results, to be practice-changing in the treatment of TNBC, by introducing the first peptide vaccine-based immunotherapy in the therapeutic choices for women with this aggressive malignancy."