Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers.

Objectives: Single-agent heat shock protein 90 (HSP90) inhibition has demonstrated activity in oncogene-driven non-small cell and small cell lung cancers. SNX-5422 is an oral HSP90 inhibitor with increased activity in vitro with the addition of carboplatin and paclitaxel. Therefore, we conducted a phase 1, open-label, multicenter study to evaluate SNX-5422, carboplatin and paclitaxel followed by SNX-5422 maintenance in patients with advanced lung cancers.

A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke).

Background: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion.

Phase I dose-escalation studies of SNX-5422, an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumours.

Background: Orally administered SNX-5422, a novel, selective prodrug of the Heat shock protein 90 (Hsp90) inhibitor SNX-2112, was investigated in two sequential phase I studies to determine the safety, maximum tolerated doses (MTDs) and pharmacokinetic profile of SNX-5422.

Methods: Using a dose-escalation design, 3-6 adults with advanced solid tumours received SNX-5422 every-other-day (QOD) or once-daily (QD) 3weeks on/1week off or QD continuously, with disease assessments every 8 weeks. Single-dose and steady-state pharmacokinetic parameters of SNX-2112 were determined.

Development of a flow cytometry-based pulse-width assay for detection of aggregates in cellular therapeutics to be infused by catheter.

Background Aims: Delivery of cell-based therapies through the carotid artery with the use of an intra-arterial catheter could introduce aggregates and cause focal ischemia in the brain. We developed a pulse-width flow cytometry method for aggregate detection and quantification. The assay was designed to be used as a cell product release assay in a clinical trial seeking to treat ischemic stroke with sorted cells brightly expressing aldehyde dehydrogenase (ALDH(br) cells) delivered through intra-arterial catheters.

Phase I trial of the HSP90 inhibitor PF-04929113 (SNX5422) in adult patients with recurrent, refractory hematologic malignancies.

Background: Heat shock protein (HSP)90 regulates the function of proteins responsible for cell growth and survival, is overexpressed in many cancers and is an attractive therapeutic target. We undertook a phase 1 trial of PF-04929113 (SNX-5422), a novel oral HSP90 inhibitor, to estimate the maximum tolerated dose and describe the pharmacokinetic and toxicity profiles.

Patients And Methods: Patients with relapsed, refractory, hematologic malignancies and adequate organ function were eligible.