William Howard Sharfman

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PURPOSE Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. (More)
PURPOSE Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or(More)
PURPOSE Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term follow-up on three patients from that trial who sustained(More)
BACKGROUND The alpha (v) beta (3) (alpha(v)beta(3)) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of etaracizumab(More)
BACKGROUND Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express(More)
BACKGROUND Bortezomib is a proteasome inhibitor with manageable clinical toxicity and laboratory evidence of anti-melanoma activity. Therefore, it was considered for clinical testing in patients with metastatic melanoma. METHODS Patients with metastatic melanoma and adequate hematologic, renal, and hepatic function were treated with bortezomib (a(More)
BACKGROUND The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. Although most patients achieve complete remission with surgical treatment, those with advanced disease have a poor prognosis. The American Joint Committee on Cancer (AJCC) is responsible for the staging criteria for all cancers. For the past 20 years, the AJCC cancer staging(More)
Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in patients with non-small cell lung cancer after initial response to immune checkpoint blockade with(More)
PURPOSE Preclinical and early clinical studies have demonstrated that initial therapy with combined BRAF and MEK inhibition is more effective in BRAF(V600)-mutant melanoma than single-agent BRAF inhibitors. This study assessed the safety and efficacy of dabrafenib and trametinib in patients who had received prior BRAF inhibitor treatment. PATIENTS AND(More)
Immune checkpoint inhibitors (ICIs) targeting cytotoxic Tlymphocyte associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and its ligand PD-L1, are established cancer immunotherapies for solid tumor and hematologic malignancies [1–10]. At present, ipilimumab, nivolumab, pembrolizumab, and the ipilimumab/nivolumab combination are U.S. Food(More)