ASCT2-Targeting Antibody-Drug Conjugate MEDI7247 in Adult Patients with Relapsed/Refractory Hematological Malignancies: A First-in-Human, Phase 1 Study.

Background: MEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer.

Objective: This first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies.

Patients And Methods: Adults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible.

First-time-in-human study of GSK923295, a novel antimitotic inhibitor of centromere-associated protein E (CENP-E), in patients with refractory cancer.

Purpose: GSK923295 is an inhibitor of CENP-E, a key cellular protein important in the alignment of chromosomes during mitosis. This was a Phase I, open-label, first-time-in-human, dose-escalation study, to determine the maximum-tolerated dose (MTD), safety, and pharmacokinetics of GSK923295.

Patients And Methods: Adult patients with previously treated solid tumors were enrolled in successive cohorts at GSK923295 doses ranging from 10 to 250 mg/m(2).

Effect of hepatic or renal impairment on the pharmacokinetics of casopitant, a NK-1 receptor antagonist.

Two studies were conducted in subjects with mild or moderate hepatic or renal impairment and subjects with normal organ function to evaluate the pharmacokinetics of casopitant and to assess its safety in these populations. A total of 26 subjects were enrolled in the hepatic impairment study and 18 subjects in the renal impairment study. All subjects received oral casopitant 100 mg once-daily for 5 days.

Effect of casopitant, a novel NK-1 receptor antagonist, on the pharmacokinetics and pharmacodynamics of steady-state warfarin.

Casopitant, a novel NK-1 receptor antagonist under investigation for the prevention of postoperative and chemotherapy-induced nausea and vomiting, is a weak to moderate inhibitor of CYP3A and a moderate inducer of CYP2C9 in vitro. Furthermore, both CYP enzymes are involved in the metabolism of R- and S-warfarin, respectively. This clinical study was conducted to explore the potential drug-drug interaction between casopitant and warfarin.

Ketoconazole and rifampin significantly affect the pharmacokinetics, but not the safety or QTc interval, of casopitant, a neurokinin-1 receptor antagonist.

Casopitant, an antiemetic, is a neurokinin-1 receptor antagonist metabolized primarily by cytochrome P450 3A4 (CYP3A4). Three phase 1 studies with 131 healthy subjects examined the impact of a strong CYP3A inhibitor (ketoconazole) and inducer (rifampin) on the pharmacokinetics and safety of casopitant. Oral casopitant was administered alone (study 1, 100-mg single dose; study 2, 150 mg on day 1, 50 mg on days 2 and 3; study 3, 150-mg single dose) with either 400 mg daily of oral ketoconazole or 600 mg daily of oral rifampin.

Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron.

Objective: The objective of this study was to characterize the impact of casopitant, a novel neurokinin-1 receptor antagonist under investigation for the prevention of postoperative and chemotherapy-induced nausea and vomiting, on the pharmacokinetics of the commonly prescribed 5-hydroxytryptamine receptor 3 receptor antagonists, dolasetron or granisetron.

Materials And Methods: In a phase I, open-label, two-part, two-period, single-sequence study, two cohorts of healthy subjects received either oral dolasetron (100 mg once daily for 3 days) or oral granisetron (2 mg once daily for 3 days) alone (period 1) and combined with oral casopitant, 150 mg day 1, 50 mg days 2 and 3 (period 2). Pharmacokinetics of hydrodolasetron and granisetron were assessed on days 1 and 3 of each period.

A dose-escalation study of recombinant human interleukin-18 using two different schedules of administration in patients with cancer.

Purpose: Interleukin-18 (IL-18) is an immunostimulatory cytokine with antitumor activity in preclinical models. A phase I study of recombinant human IL-18 (rhIL-18) was done to determine the toxicity, pharmacokinetics, and biological activities of rhIL-18 administered at different doses in two different schedules to patients with advanced cancer.

Experimental Design: Cohorts of three to four patients were given escalating doses of rhIL-18 as a 2-h i.