A Phase 3 Randomized, Open-Label Study of Nivolumab (Anti-Pd-1; Bms-936558; Ono-4538) Versus Investigator'S Choice Chemotherapy (Icc) in Patients with Advanced Melanoma After Prior Anti-Ctla-4 Therapy

Weber, Jeffrey S.; Minor, David R.; D’Angelo, Sandra P.; Hodi, F. Stephen; Gutzmer, Ralf; Neyns, Bart; Höeller, Christoph; Khushalani, Nikhil I.; Miller, Wilson H.; Grob, J.J.; Lao, Christopher D.; Linette, Gerald P.; Grossmann, Kenneth F.; Hassel, J.C.; Lorigan, Paul; Maio, Michele; Sznol, Mario; Lambert, Alexandre; Yang, Allison L.; Larkin, James

doi:10.1093/annonc/mdu438.34

Cited by 57 publications

(33 citation statements)

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“…Response rates to nivolumab were 44% among patients whose tumors expressed PD-L1 compared with 20% of patients with PD-L1-negative tumors. 7 These data supported the US Food and Drug Administration’s (FDA) 2014 approval of nivolumab as therapy for patients with advanced melanoma refractory to ipilimumab and, for BRAF-mutant tumors, a BRAF inhibitor.…”

Section: Melanomamentioning

confidence: 64%

Antagonists of PD-1 and PD-L1 in Cancer Treatment

Lipson

Forde

Hammers

et al. 2015

Seminars in Oncology

276

199

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The PD-1 pathway, comprising the immune cell co-receptor Programmed Death 1 (PD-1) and its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), mediates local immunosuppression in the tumor microenvironment. Drugs designed to block PD-1 or PD-L1 “release the brakes” on anti-tumor immunity and have demonstrated clinical activity in several types of advanced cancers, validating this pathway as a target for cancer therapy. Two such drugs have recently been approved to treat refractory advanced melanoma, and regulatory approvals in first- and second-line settings for additional cancer types are anticipated. The manageable safety profile of PD-1/PD-L1 blocking drugs identifies them as suitable for outpatient administration and the development of combinatorial therapies. Ongoing studies aim to identify biomarkers to guide patient selection, which would further improve the risk:benefit ratio for these drugs.

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Section: Melanomamentioning

confidence: 64%

Antagonists of PD-1 and PD-L1 in Cancer Treatment

Lipson

Forde

Hammers

et al. 2015

Seminars in Oncology

276

199

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“…A randomised phase 3 study comparing another PD-1 inhibitor, nivolumab, with investigators choice chemotherapy (ICC) after failure of ipilimumab demonstrated higher response rates with nivolumab (51% vs 35%). This was despite a higher incidence of adverse prognostic factors in the nivolumab arm [9].…”

Section: Introductionmentioning

confidence: 87%

Optimal management of immune-related toxicities associated with checkpoint inhibitors in lung cancer

et al. 2015

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“…Pembrolizumab produced a 26% response rate in this patient population, and, at most recent data analysis, 88% (36/41) of patients with objective responses had ongoing responses at follow-up of 1.4 to 8.5+ months [120]. Nivolumab produced responses in 32% of patients compared to 11% response rate in chemotherapy arm, with 87% (33/38) of patients having ongoing responses at follow up of 2.6 to 10+ months [121]. …”

Section: Emerging Role Of Immune Checkpoints In Immune Escape By Amentioning

confidence: 99%

Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia

Knaus¹,

Kanakry²,

Luznik³

et al. 2017

CDT

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Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body’s own immune system to fight leukemic cells.

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A Phase 3 Randomized, Open-Label Study of Nivolumab (Anti-Pd-1; Bms-936558; Ono-4538) Versus Investigator'S Choice Chemotherapy (Icc) in Patients with Advanced Melanoma After Prior Anti-Ctla-4 Therapy

Cited by 57 publications

References 0 publications

Antagonists of PD-1 and PD-L1 in Cancer Treatment

Antagonists of PD-1 and PD-L1 in Cancer Treatment

Optimal management of immune-related toxicities associated with checkpoint inhibitors in lung cancer

Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia

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