A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development.

Exposure-response (E-R) analyses are an integral component in the development of oncology products. Characterizing the relationship between drug exposure metrics and response allows the sponsor to use modeling and simulation to address both internal and external drug development questions (e.g.

A unique series of chromium(iii) mono-alkynyl complexes supported by tetraazamacrocycles.

Described herein is the synthesis and characterization of macrocyclic Cr mono-alkynyl complexes. By using the meso-form of the tetraazamacrocycle HMC (HMC = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane), trans-[Cr(HMC)(CPh)Cl]OTf (1a), trans-[Cr(HMC)(CNp)Cl]OTf (2a), trans-[Cr(HMC)(CCHBu)Cl]OTf (3a), and trans-[Cr(HMC)(C(3,5-ClCH))Cl]OTf (4a) complexes have been realized. These complexes were synthesized in high yield through the reaction of trans-[Cr(meso-HMC)(CAr)]OTf (1b-4b) with stoichiometric amounts of methanolic HCl.

Immunogenicity of pembrolizumab in patients with advanced tumors.

Background: Pembrolizumab is a potent, humanized, monoclonal anti-programmed death 1 antibody that has demonstrated effective antitumor activity and acceptable safety in multiple tumor types. Therapeutic biologics can result in the development of antidrug antibodies (ADAs), which may alter drug clearance and neutralize target binding, potentially reducing drug efficacy; such immunogenicity may also result in infusion reactions, anaphylaxis, and immune complex disorders. Pembrolizumab immunogenicity and its impact on exposure, safety, and efficacy was assessed in this study.

Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE-029 Study.

Pembrolizumab monotherapy, ipilimumab monotherapy, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC. The phase Ib KEYNOTE-029 study (ClinicalTrials.