Amgen has announced the initiation of a clinical trial, NCT02366195, to determine whether baseline CD8+ T lymphocytes density is a biomarker of response to talimogene laherparepvec, an investigational oncolytic immunotherapy, in patients with unresected stages IIIB to IV melanoma. The first subject has enrolled into the study, with the goal of including approximately 110 patients across 49 clinical trial sites in 11 different countries in Europe.

CD8+ T lymphocytes are also known as killer, or cytotoxic T lymphocytes that express CD8 on the cell surface. CD8+ T lymphocytes are a critical component of the cellular immune response and they play a central role in destroying cancer cells and cells infected with viruses.

"Tumor-infiltrating CD8+ T cells are frequently associated with favorable clinical outcomes in a spectrum of cancers and we hope this trial will help us find those patients for whom talimogene laherparepvec may be most beneficial," said study investigator, Dr. Josep Malvehy, director of the Melanoma Unit, Dermatology Department, Hospital Clinic of Barcelona in Spain. "We expect the role of immunological biomarkers to increase significantly in the next few years, enabling personalized anti-cancer immunotherapy with optimal treatment selection for individual tumors, which is important for patients."

"We now know that infiltration of tumors by CD8+ T lymphocytes is emerging as a prognostic marker in many tumor types and may be predictive for response to immunotherapies. With this new study, we are excited to learn whether the change in the density of infiltrating intratumoral CD8 compared to baseline after talimogene laherparepvec treatment may help identify patients with regionally and distantly metastatic melanoma who might benefit from this treatment," said David Reese, M.D., senior vice president of Translational Sciences at Amgen. "Studies such as these are the important first step required to investigate potential prognostic and predictive biomarkers in patients who may respond to talimogene laherparepvec."

A Biologics License Application (BLA) and a Marketing Authorization Application for talimogene laherparepvec for the treatment of patients with regionally or distantly metastatic melanoma was accepted for review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), respectively. Amgen recently announced that the Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) and the Oncologic Drugs Advisory Committee (ODAC) of the FDA will jointly review the Company's BLA for talimogene laherparepvec.

The regulatory filings included data from more than 400 patients treated with talimogene laherparepvec and are based on a global, randomized, open-label Phase 3 trial evaluating the safety and efficacy of intralesional talimogene laherparepvec in patients with unresected stage IIIB, IIIC, or IV melanoma compared to granulocyte-macrophage colony-stimulating factor (GM-CSF).

About the Trial

The multicenter, Phase 2, single arm study is designed to evaluate the correlation between the baseline intratumoral CD8+ T lymphocytes density and objective tumor response rate and other efficacy end points in subjects with unresected stage IIIB to IVM1c melanoma treated with talimogene laherparepvec.

The study is scheduled to take approximately 32 months following the first patient enrolled. No formal statistical hypothesis will be tested in this trial. The study will explore the hypothesis that intratumoral CD8+ cell density at baseline correlates with objective response rate in subjects with unresected stage IIIB to IVMIc melanoma treated with talimogene laherparepvec.The primary endpoint of this trial is the correlation between baseline intratumoral CD8+ cell density and objective response rate. Secondary endpoints include correlation between changes in intratumoral CD8+ cell density during treatment (in injected and uninjected lesions) and ORR, DRR, DOR, and changes in tumor burden.

About Talimogene Laherparepvec

Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Talimogene laherparepvec was designed to work in two important and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor's cells causing the cell to rupture and die in a process called lysis. Then, the rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, that can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body.

Amgen has initiated a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.