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First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors.
  • T. Yap, Li Yan, A. Tolcher
  • Medicine, Biology
    Journal of clinical oncology : official journal…
  • 10 December 2011
TLDR
MK-2206 was well tolerated, with evidence of AKT signaling blockade, and Rational combination trials are ongoing to maximize clinical benefit with this therapeutic strategy.
Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors.
TLDR
Abemaciclib represents the first selective inhibitor of CDK4 and CDK6 with a safety profile allowing continuous dosing to achieve sustained target inhibition, and this first-in-human experience demonstrates single-agent activity for patients with advanced breast cancer, NSCLC, and other solid tumors.
PD‐1 Blockade with Cemiplimab in Advanced Cutaneous Squamous‐Cell Carcinoma
TLDR
Among patients with advanced cutaneous squamous‐cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors.
The KRASG12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers in Mouse Models and Patients.
TLDR
Comprehensive pharmacodynamic and pharmacogenomic profiling in sensitive and partially resistant non-clinical models identified mechanisms implicated in limiting anti-tumor activity including KRAS nucleotide cycling and pathways that induce feedback reactivation and/or bypass KRAS dependence.
Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors
TLDR
Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors, and Mechanism-based translational models with a focus on intratumor exposure prediction suggested robust clinical activity would be observed at doses ≥2 mg/kg every 3 weeks.
Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors.
TLDR
RO4929097 was well tolerated at 270mg on schedule A and at 135 mg on schedule B; the safety of schedule C has not been fully evaluated and further studies are warranted on the basis of a favorable safety profile and preliminary evidence of clinical antitumor activity.
Clinical Pharmacokinetics, Metabolism, and Drug-Drug Interaction of Carfilzomib
TLDR
It is concluded that the rapid systemic clearance and short half-life of carfilzomib limit clinically significant DDI and there were no safety signals indicative of potential drug interactions.
The Clinical Effect of the Dual-Targeting Strategy Involving PI3K/AKT/mTOR and RAS/MEK/ERK Pathways in Patients with Advanced Cancer
TLDR
The results suggest that dual inhibition of both pathways may potentially exhibit favorable efficacy compared with inhibition of either pathway, at the expense of greater toxicity.
A phase I dose-escalation trial of 2-deoxy-d-glucose alone or combined with docetaxel in patients with advanced solid tumors
TLDR
The recommended dose of 2DG in combination with weekly docetaxel is 63 mg/kg/day with tolerable adverse effects, and this phase I trial found this to be the clinically tolerable dose.
Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1.
TLDR
AMG 479 can be administered safely at 20 mg/kg IV Q2W and the absence of severe toxicities, attainment of serum concentrations associated with high levels of IGF-1R binding on neutrophils, and provocative antitumor activity warrant additional studies of this agent.
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