Oncothyreon Inc. (Nasdaq: ONTY) today announced the initiation of a Phase 1/2 trial of PX-866 in combination with vemurafenib (Zelboraf®). 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. Vemurafenib is a kinase inhibitor indicated for the treatment of unresectable or metastatic melanoma with the BRAFV600E mutation.
The Phase 1 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 2. The Phase 2 portion of the trial will compare the anti-tumor activity and safety of PX-866 and vemurafenib at the doses recommended from Phase 1 with vemurafenib alone administered at the approved dose. This randomized Phase 2 trial is expected to enroll 110 patients with advanced BRAF-mutant melanoma and has a primary endpoint of progression-free survival.
This Phase 1/2 trial is being conducted in collaboration with the Melanoma Research Foundation Breakthrough Consortium (MRFBC). Lynn M. Schuchter, M.D., Chief of the Hematology Oncology Division and leader of the melanoma program at the Abramson Cancer Center 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, M.D., President and Chief Executive Officer of Oncothyreon. “With the initiation of this trial, Oncothyreon is now conducting five Phase 2 trials of PX-866 in six different tumor types, a broad development program reflecting our enthusiasm for this product candidate.”