Oncothyreon Inc., a biotechnology company specializing in the development of innovative therapeutic products for the treatment of cancer, has started phase I/II trial of PX-866 in combination with vemurafenib (Zelboraf), a kinase inhibitor indicated for the treatment of unresectable or metastatic melanoma with the BRAFV600E mutation.

PX-866 is Oncothyreon's investigational small molecule compound designed to inhibit the activity of phosphatidylinositol-3-kinase (PI-3K), a component of an important cell survival signaling pathway.

The phase I portion of this trial will evaluate the safety and tolerability of PX-866 in combination with twice daily oral administration of vemurafenib in up to 36 patients with any BRAF-mutant cancer. The trial will use a dose-escalation design to evaluate up to three dose levels of PX-866 with up to two dose levels of vemurafenib to determine the maximally tolerated or recommended dose of both PX-866 and vemurafenib to be used in phase II. The phase II portion of the trial will compare the anti-tumor activity and safety of PX-866 and vemurafenib at the doses recommended from phase I with vemurafenib alone administered at the approved dose. This randomized phase II trial is expected to enroll 110 patients with advanced BRAF-mutant melanoma and has a primary endpoint of progression-free survival.

This phase I/II trial is being conducted in collaboration with the Melanoma Research Foundation Breakthrough Consortium (MRFBC). Lynn M Schuchter, MD, Chief of the Haematology Oncology Division and leader of the melanoma programme at the Abramson Cancer Centre of the University of Pennsylvania, a member of the MRFBC, said, “While vemurafenib has significantly prolonged the lives of patients with BRAF-mutant melanoma, many patients develop resistance.  Preclinical evidence suggests that the PI-3 kinase pathway may contribute to this resistance, and we are therefore excited to begin this study.”

“We are grateful to the MRFBC for proposing and performing this study,” said Robert L Kirkman, MD, president and CEO of Oncothyreon. “With the initiation of this trial, Oncothyreon is now conducting five phase II trials of PX-866 in six different tumor types, a broad development program reflecting our enthusiasm for this product candidate.”

The mission of the Melanoma Research Foundation Breakthrough Consortium (MRFBC) is to accelerate research and development of the most promising therapeutics in melanoma to deliver curative treatment options to patients. The MRFBC works through collaborative private, public and nonprofit partnerships to facilitate, conduct or enhance the development of the most promising combination therapies - a strategy which has been shown to be the cornerstone of success in treating diseases such as TB and HIV. Clinical trials supported by the MRFBC are opening this year.

PX-866 is a pan inhibitor of the PI-3K/PTEN/AKT pathway, a critical cell signaling pathway that is activated in many types of human cancer. Aberrant activation and regulation of PI-3K is implicated in a large proportion of human cancers, where it leads to increased proliferation and inhibition of apoptosis (programmed cell death).

Oncothyreon is conducting a broad development program of PX-866 as a single agent and in combination with other agents in multiple cancer types. In addition to the above trial, current trials include a phase I/II trial of PX-866 in combination with cetuximab (Erbitux) in patients with metastatic colorectal carcinoma or progressive, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) and a phase I/II trial of PX-866 in combination with the chemotherapeutic agent docetaxel in patients with locally advanced, recurrent or metastatic non-small cell lung cancer or SCCHN. In addition, the NCIC Clinical Trials Group is conducting two Phase 2 trials, one in patients with recurrent or metastatic castration- resistant prostate cancer and one in patients with glioblastoma multiforme that has recurred during or following primary therapy.

Oncothyreons' goal is to develop and commercialize novel synthetic vaccines and targeted small molecules that have the potential to improve the lives and outcomes of cancer patients.