Archer Biosciences initiates third drug-escalation cohort in TPI-287 trial for metastatic melanoma

Archer Biosciences, Inc. announced that the trial of its novel, proprietary drug TPI-287 (an abeotaxane) for the treatment of metastatic melanoma has initiated a third drug-escalation cohort. The primary objective of this study is to determine the safety, tolerability and maximum tolerated dose (MTD) of TPI-287 in combination with temozolomide (TMZ) in adult patients with metastatic melanoma. The study includes patients with disease metastatic to the brain as TPI-287, avoids the multidrug resistant (MDR) efflux pump and has demonstrated in pre-clinical studies its ability to cross the blood brain barrier.

In this trial, successive cohorts of three patients per cohort with refractory or recurrent metastatic melanoma are treated with escalating doses of both TPI-287 (given intravenously weekly for three weeks of every four week cycle) and Temozolamide (given daily for the first five days of the four week cycle). Doses of TPI-287 at 90mg/m² then 110mg/m² were administered to the first two cohorts, respectively, and were combined with 85 mg/m² TMZ. The third cohort is currently receiving TPI-287 at 125mg/m² and TMZ at 85mg/m².

It is known that TPI-287 is active in animal models of human melanoma. In addition, TPI-287 administered intravenously can penetrate the brain parenchyma to reach pharmacologically and clinically relevant levels, inasmuch as the drug demonstrated activity in an orthotopic model of glioblastoma. In this study, animals receiving TPI-287 in combination with TMZ had significantly improved overall survival compared to animals receiving no drugs or either of these drugs alone. These data suggest that tumors metastatic to the brain are an appropriate target for TPI-287 therapy. Numerous studies establishing the safety and efficacy of TPI-287 in over 100 adult patients with cancer have already been conducted.

The study is being conducted with the Department of Melanoma Medical Oncology under the direction of principal investigator, Agop Y. Bedikian, M.D. at the M.D. Anderson Cancer Center.