Hana initiates PI/II NSCLC trial

Hana Biosciences, a biopharmaceutical company headquartered in San Francisco, CA, US, has initiated a Phase I/II clinical trial of PT-523 as a single agent in relapsed non-small cell lung cancer (NSCLC).

The Phase I component of the new study is a multi-centre, multi-national trial which will first determine the dose, safety, tolerability, pharmacokinetics and preliminary efficacy of PT-523 in NSCLC patients (second and third line patients). The Phase II component will utilise the maximally tolerated dose (MTD) in the same schedule, with the primary efficacy endpoint being overall survival. Secondary endpoints will include time-to-progression (TTP), progression-free survival (PFS), response rate (RR), and safety/tolerability. The trial is expected to enroll between 80-120 patients over the next 12 to 15 months. Several leading clinical research sites in the US and Eastern Europe are expected to participate in the trial.

PT-523 is currently completing a Phase I trial in patients with advanced solid tumours. This trial is being conducted at the Dana-Farber Cancer Institute, Massachusetts General Hospital, and Beth Israel-Deaconess Hospital. The new study will focus specifically on relapsed non-small cell lung cancer patients using a more common dosing schedule for lung cancer treatment.

'With five year overall survival currently at 10-15%, improving the standard of care for non-small lung cancer patients is an important priority for the oncology community. We look forward to exploring the potential of PT-523 in this patient population,' said Dr Ravi Salgia, director, thoracic oncology research program and associate professor of medicine, University of Chicago and one of the lead investigators on the new study.

'The initiation of this study marks another important milestone in the development of PT-523. The level of interest in this compound in the academic oncology community has been very encouraging, and we are particularly pleased that several leading lung cancer experts are involved with this clinical trial,' commented Dr Greg Berk, chief medical officer and vice-president of Hana Biosciences. In addition, Hana is planning trials with PT-523 in gynecologic cancers and lymphoid leukaemias.

PT-523

PT-523 is a novel, non-classical antifolate that is a water-soluble, nonpolyglutamatable analogue of aminopterin. Potential advantages of PT-523 include increased targeting to tumour cells, better tolerability and a superior resistance profile over existing therapies. PT-523 is 10-fold more efficiently transported by the membrane-bound transporter RFC into cells, 10-fold more tightly bound to the target enzyme, DHFR, and 10 to 100-fold more efficacious in a wide variety of tumour cell lines and animal models compared with methotrexate (MTX). PT-523 has also demonstrated efficacy in MTX resistant tumour models. Thus, PT-523 is a potentially exciting anticancer product because it enters the cell more efficiently because of increased water solubility, works through an established and proven mechanism of action, overcomes resistance typically associated with this class of therapies and selectively binds to the key target enzyme.