Safety, pharmacokinetics (PK) and pharmacodynamics (PD) data from a phase I dose-escalation study of OX40 agonistic monoclonal antibody (mAb) PF-04518600 (PF-8600) in combination with utomilumab, a 4-1BB agonistic mAb

Hamid, Omid; Ros, Willeke; Thompson, John A.; Hu‐Lieskovan, Siwen; Eskens, Fredericus; Diab, Adi; Doi, Toshihiko; Wasser, Jeffrey S.; Jp, Spano; Rizvi, Naiyer A.; Angevin, Eric; Chiappori, Alberto; Ott, Patrick A.; Ganguly, Bishu; Fleener, Catherine; Dell, Vanessa; Liao, Kuo‐Wei; Joh, Tenshang; Chou, Jeffrey; El-Khoueiry, A.

doi:10.1093/annonc/mdx376.008

Cited by 2 publications

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“…Regarding the 4 evaluable urothelial cancer patients, 2 experienced stable disease (50%) and 2 progressive disease (50%) as best response. Biomarker analysis showed that combination treatment resulted in greater increases in expression of activation and proliferation markers on CD8 memory T cells, in particular, and memory T-cell subsets overall, than with PF-04518600 alone (31).…”

Section: Combinations With Ox40 Agonistsmentioning

confidence: 97%

“…A phase I doseescalation study is testing the safety and preliminary anticancer activity of PF-04518600 in combination with utomilumab in advanced solid tumors (NCT02315066; Table 2; ref. 31). Because OX40 acts predominantly on CD4 T-cell function, while 4-1BB primarily impacts on CD8 T-cell and natural killer cell function, dual stimulation of both OX40 and 4-1BB has been postulated as a promising treatment combination.…”

Section: Combinations With Ox40 Agonistsmentioning

confidence: 99%

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Immunotherapy Combinations and Sequences in Urothelial Cancer: Facts and Hopes

Rodríguez‐Vida

Perez-Gracia

Bellmunt

2018

Clinical Cancer Research

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Immune checkpoint inhibitors (ICI) have emerged as a novel therapeutic strategy that achieves significant clinical benefit in several tumor types, including urothelial cancer. Overall, these agents have shown objective response rates of around 20% to 23%, which indicates that a significant proportion of patients do not benefit from immunotherapy when given as monotherapy. Moreover, despite an initial response to therapy and an improvement in the median duration of response compared with chemotherapy, still only half of the patients develop long-term maintained remissions. Active research is ongoing in several fields, aiming to increase the number of patients that benefit from ICI, and this research is largely based on the development of biomarkers for personalized immunotherapy and novel combinations of ICI with other agents. This article will review ongoing efforts to develop combinations of ICI with other therapeutic strategies in patients with urothelial cancer, including chemotherapy, targeted agents, other immunotherapy strategies, and radiotherapy.

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Section: Combinations With Ox40 Agonistsmentioning

confidence: 97%

Section: Combinations With Ox40 Agonistsmentioning

confidence: 99%

Immunotherapy Combinations and Sequences in Urothelial Cancer: Facts and Hopes

Rodríguez‐Vida

Perez-Gracia

Bellmunt

2018

Clinical Cancer Research

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Emerging therapeutic agents for genitourinary cancers

Zarrabi

Paroya

2019

J Hematol Oncol

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The treatment of genitourinary malignancies has dramatically evolved over recent years. Renal cell carcinoma, urothelial carcinoma of the bladder, and prostate adenocarcinoma are the most commonly encountered genitourinary malignancies and represent a heterogeneous population of cancers, in both histology and approach to treatment. However, all three cancers have undergone paradigm shifts in their respective therapeutic landscapes due to a greater understanding of their underlying molecular mechanisms and oncogenic drivers. The advance that has gained the most recent traction has been the advent of immunotherapies, particularly immune checkpoint inhibitors. Immunotherapy has increased overall survival and even provided durable responses in the metastatic setting in some patients. The early success of immune checkpoint inhibitors has led to further drug development with the emergence of novel agents which modulate the immune system within the tumor microenvironment. Notwithstanding immunotherapy, investigators are also developing novel agents tailored to a variety of targets including small-molecule tyrosine kinase inhibitors, mTOR inhibitors, and novel fusion proteins to name a few. Erdafitinib has become the first targeted therapy approved for metastatic bladder cancer. Moreover, the combination therapy of immune checkpoint inhibitors with targeted agents such as pembrolizumab or avelumab with axitinib has demonstrated both safety and efficacy and just received FDA approval for their use. We are in an era of rapid progression in drug development with multiple exciting trials and ongoing pre-clinical studies. We highlight many of the promising new emerging therapies that will likely continue to improve outcomes in patients with genitourinary malignancies.

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Safety, pharmacokinetics (PK) and pharmacodynamics (PD) data from a phase I dose-escalation study of OX40 agonistic monoclonal antibody (mAb) PF-04518600 (PF-8600) in combination with utomilumab, a 4-1BB agonistic mAb

Cited by 2 publications

References 0 publications

Immunotherapy Combinations and Sequences in Urothelial Cancer: Facts and Hopes

Immunotherapy Combinations and Sequences in Urothelial Cancer: Facts and Hopes

Emerging therapeutic agents for genitourinary cancers

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