Phase II study of the antibody-drug conjugate TAK-264 (MLN0264) in patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing guanylyl cyclase C.

Background The first-in-class antibody-drug conjugate TAK-264 (formerly MLN0264) consists of an antibody targeting guanylyl cyclase C (GCC) conjugated to monomethyl auristatin E (MMAE) via a peptide linker. This phase II study evaluated the efficacy and safety of TAK-264 in patients with adenocarcinoma of the stomach or gastroesophageal junction expressing GCC, who had progressed on ≥1 line of prior therapy. Methods This study used a two-stage design, with an interim analysis conducted after stage I to determine whether to continue to stage II or discontinue on the grounds of futility.

Phase I Study of the Investigational Anti-Guanylyl Cyclase Antibody-Drug Conjugate TAK-264 (MLN0264) in Adult Patients with Advanced Gastrointestinal Malignancies.

Purpose: To assess the safety, tolerability, and preliminary antitumor activity of the investigational anti-guanylyl cyclase C (GCC) antibody-drug conjugate TAK-264 (formerly MLN0264) in adult patients with advanced gastrointestinal malignancies.

Experimental Design: Adult patients with GCC-expressing gastrointestinal malignancies (H-score ≥ 10) were eligible for inclusion. TAK-264 was administered as a 30-minute intravenous infusion once every 3 weeks for up to 17 cycles.

Brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive haematologic malignancies and hepatic or renal impairment.

Aims: Brentuximab vedotin, an antibody-drug conjugate (ADC), selectively delivers the microtubule-disrupting agent monomethyl auristatin E (MMAE) into CD30-expressing cells. The pharmacokinetics of brentuximab vedotin have been characterized in patients with CD30-positive haematologic malignancies. The primary objective of this phase 1 open label evaluation was to assess the pharmacokinetics of brentuximab vedotin in patients with hepatic or renal impairment.

Pharmacokinetic properties of infliximab in children and adults with Crohn's disease: a retrospective analysis of data from 2 phase III clinical trials.

Background: Infliximab is a chimeric monoclonal antibody against TNFα. The pharmacokinetic (PK) properties of infliximab have been studied in several adult patient populations, but a literature search identified no reported comparative population PK properties of this drug in pediatric patients.

Objectives: The current analysis applied population PK techniques to compare data on the PK properties of infliximab in pediatric and adult patients with moderately to severely active Crohn's disease (CD) from 2 Phase III studies.

Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis.

Purpose: Infliximab, a monoclonal antibody, is approved for the treatment of inflammatory diseases at doses that depend on the patient disease population. It was the aim of this study to evaluate its population pharmacokinetics in patients with moderately to severely active ulcerative colitis and characterize patient covariates that affect its disposition in this population.

Methods: Information collected from 482 patients in two randomized, double-blind, placebo-controlled international studies were analyzed using NONMEM.

Absence of adverse effects in cynomolgus macaques treated with CNTO 95, a fully human anti-alphav integrin monoclonal antibody, despite widespread tissue binding.

Purpose: CNTO 95 is a fully human anti-alphav integrin monoclonal antibody that inhibits macaque and rodent angiogenesis and inhibits human tumor growth in rodents. The purpose of these studies was to evaluate the preclinical safety of long-term administration of CNTO 95 in cynomolgus macaques.

Experimental Design: The in vitro binding profiles of CNTO 95 to human and macaque tissues and the in vivo binding to macaque tissues was evaluated by immunohistochemistry.

Kinetics of thermal decomposition of 4-carboxyl-2,6-dinitrobenzenediazonium ion (CDNBD).

The kinetics of thermal decomposition of 4-carboxyl-2,6-dinitrobenzenediazonium ion (CDNBD), an arenediazonium ion newly developed as a derivatizing reagent for drug analysis, are described. The arenediazonium ion, in an optimized concentrated sulfuric acid/orthophosphoric acid medium, was incubated for various time intervals at 30 degrees, 45 degrees, 55 degrees , 65 degrees , 75 degrees, and 85 degrees C. The amount of ion left after each time interval was quantified selectively by colorimetric assay at 490 nm, using mefenamic acid as a model diazo-coupling component.

Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial.

Background: Preclinical and preliminary clinical data have suggested that tumor necrosis factor-alpha (TNFalpha) may play a role in the evolution and progression of heart failure and that inhibition of TNFalpha may favorably modify the course of the disease. We evaluated the efficacy and safety of infliximab, a chimeric monoclonal antibody to TNFalpha, in patients with moderate-to-severe heart failure.

Methods And Results: One hundred fifty patients with stable New York Heart Association class III or IV heart failure and left ventricular ejection fraction View Article and Find Full Text PDF

Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-alpha monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris.

Objective: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial.

Methods: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6.

The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial.

Objective: To investigate the relationship between serum concentrations of infliximab, a monoclonal anti-tumor necrosis factor alpha antibody, and clinical improvement from infliximab therapy for rheumatoid arthritis (RA).

Methods: Multiple blood samples were obtained from each of 428 subjects with active RA who were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (ATTRACT [Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy]) evaluating the clinical efficacy and safety of infliximab therapy. Serum levels of infliximab were measured by enzyme-linked immunosorbent assay.