Amgen has initiated a trial of talimogene laherparepvec, an investigational oncolytic immunotherapy, in combination with an investigational use of Merck's FDA approved, anti-PD-1 therapy, Keytruda (pembrolizumab) in patients with regionally or distantly metastatic melanoma. The trial has enrolled its first patient and will evaluate the combination of these two therapies in approximately 110 patients across 35 clinical trial sites in the U.S., Australia and Europe.

"Data from this trial will help us further understand the safety and efficacy that comes from combining two immunotherapeutic agents," said F. Stephen Hodi, M.D., director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Cancer Institute and Steering Committee Chair for this study. "Talimogene laherparepvec is designed to promote tumor antigen release and presentation to initiate an anti-tumor immune response, which may be complementary to Keytruda's role in releasing PD-1 pathway-mediated inhibition of anti-tumor immune responses. Antigen release and presentation is a fundamental step required for mounting a systemic effect against melanoma, and we think there is a strong rationale for combining the oncolytic immunotherapy talimogene laherparepvec with the immune checkpoint inhibitor Keytruda."

Sean E. Harper, M.D., executive vice president of R&D at Amgen, said, "We are excited to partner with Merck and explore the potential of talimogene laherparepvec and Keytruda. This also will give us insights into talimogene laherparepvec beyond the monotherapy setting, where a phase III trial has shown encouraging results."

A Biologics License Application has recently been accepted for review by the FDA as has a Marketing Authorization Application in the E.U. for talimogene laherparepvec for the treatment of patients with regionally or distantly metastatic melanoma. The FDA has set a review goal date under the Prescription Drug User Fee Act (PDUFA) of July 28, 2015.

The regulatory filings included data from more than 400 patients and is based on a global, randomized, open-label phase III trial evaluating the safety and efficacy of intralesional talimogene laherparepvec in patients with stage IIIB, IIIC or IV melanoma that are not surgically resectable compared to granulocyte-macrophage colony-stimulating factor (GM-CSF). An Amgen-sponsored expanded access protocol (EAP) is currently active for qualified patients with unresected, stage IIIB to IV melanoma who are not eligible for or who cannot access ongoing talimogene laherparepvec trials.

The multicenter, open-label clinical trial is designed to evaluate the safety of talimogene laherparepvec in combination with Keytruda, as well as the efficacy of this combination versus Keytruda alone and following progression after treatment with Keytruda alone.

The study will be conducted in two phases:

• Phase I will determine the safety and tolerability of talimogene laherparepvec in combination with Keytruda in patients with previously untreated, unresected, stage IIIB to IVM1c melanoma.
• The randomized phase will further evaluate the safety and efficacy of talimogene laherparepvec in combination with Keytruda.