598 A Phase 1b Study of Demcizumab Plus Pemetrexed and Carboplatin in Patients with 1st Line Non-Small Cell Lung Cancer (NSCLC)

McKeage, Mark J.; Kotasek, Dusan; Millward, Michael; Markman, B.; Jameson, Michael B.; Hidalgo, María Jesús Cancelo; Harris, D.; Stagg, Robert; Dupont, Jakob; Hughes, Brett Gordon Maxwell

doi:10.1016/s0959-8049(12)72395-x

Cited by 5 publications

(2 citation statements)

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“…OMP-21M18 plus pemetrexed and carboplatin phase 1b trial has reported a 44% PR and 94% disease control rate (PR + SD) among 17 evaluable advanced NSCLC patients. Fatigue and hypertension were the most common drug-related toxicities (McKeage et al, 2012). …”

Section: Agents Targeting Notch Signaling Pathwaymentioning

confidence: 99%

Targeting Notch signaling pathway in cancer: Clinical development advances and challenges

Takebe

Nguyen

Yang

2014

Pharmacology & Therapeutics

350

263

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Notch signaling plays an important role in development and cell fate determination, and it is deregulated in human hematologic malignancies and solid tumors. This review includes a brief introduction of the relevant pathophysiology of Notch signaling pathway and primarily focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as γ-secretase inhibitors (GSIs) or interfere with the Notch ligand–receptor interaction by monoclonal antibodies (mAbs). Antitumor activity by GSIs and mAbs administered as single agent in early phases of clinical trials has been observed in advanced or metastatic thyroid cancer, non-small cell lung cancer, intracranial tumors, sarcoma or desmoid tumors, colorectal cancer with neuroendocrine features, melanoma and ovarian cancer. A number of mechanism-based adverse events particularly gastrointestinal toxicities emerged and mitigation strategies are developed after testing multiple GSIs and Notch targeting mAbs. We also discuss pharmacodynamic biomarkers in conjunction with methods of assessment of the molecular target inhibition validation. Biomarkers of efficacy or benefit may be of importance for a successful development of this class of drugs.

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Section: Agents Targeting Notch Signaling Pathwaymentioning

confidence: 99%

Targeting Notch signaling pathway in cancer: Clinical development advances and challenges

Takebe

Nguyen

Yang

2014

Pharmacology & Therapeutics

350

263

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“…Demcizumab is a humanised monoclonal antibody that blocks DLL4. In a phase Ib study, demcizumab showed some activity in combination with carboplatin and pemetrexed in non-squamous NSCLC in the first line setting [ 114 ]. This has led to a phase II study, which is currently recruiting.…”

Section: Current Therapies Availablementioning

confidence: 99%

The Evolution of Therapies in Non-Small Cell Lung Cancer

Boolell¹,

Alamgeer²,

Watkins³

et al. 2015

Cancers

107

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The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 receptor (PD-1), which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

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