BCC020: Difluoromethylornithine (DFMO) and AMXT 1501

Summary

AMXT 1501 will be used in an open label, multicenter, study in combination with Difluoromethylornithine (DFMO) for subjects with neuroblastoma (NBL), CNS tumors (DIPG, ATRT, ETMR), and sarcomas(Ewing and Rhabdomyosarcoma). The Phase I portion of the study uses a standard 3+3 design in which groups of 3 subjects will receive 28-day cycles of oral AMXT 1501 combined with DFMO for up to 24 cycles. For phase II, all cohorts besides NBL will receive AMXT 1501 and DFMO as the dose level identified in Phase I to evaluate efficacy. NBL subjects will be randomized to receive the combination or DFMO alone with the ability to cross over to the combination once their endpoint is met.

Trial Information

What is AMXT 1501 and DFMO?

AMXT 1501 is an oral small molecule polyamine uptake inhibitor, while DFMO is a polyamine synthesis inhibitor recently FDA approved to prevent relapse in high-risk neuroblastoma. AMXT 1501 is designed to work in conjunction with DFMO to constrain the production and uptake of polyamines – molecules found in high concentrations in cancer cells and linked to immune system suppression. Reducing polyamines and, in turn, decreasing myeloid-derived suppressor cells in the tumor microenvironment, allows for activation of the immune system to attack solid tumors.

Approach

Primary Objective:

Phase I:

To evaluate the safety, tolerability, and recommended phase 2 dose (RP2D) of AMXT-1501 in combination with DFMO in pediatric and young adult patients.

Phase II:

To evaluate the activity of AMXT-1501 in combination with DFMO on: Progression free survival (PFS) and Overall response rate (ORR)
To evaluate the pharmacokinetics (PK) of AMXT-1501 and DFMO in the blood and CSF.

Secondary Objectives:

Phase I:

To evaluate, in a prospective clinical trial, the efficacy of difluoromethylornithine (DFMO) in combination with AMXT-1501 in 4 separate disease cohorts based upon PFS.

Phase II:

To evaluate the efficacy of DFMO in combination with AMXT 1501 in 4 disease cohorts outlined above, based upon: Overall response rate (ORR) and Overall Survival (OS)
To evaluate the safety and tolerability profile of DFMO in combination with AMXT 1501 in pediatric and young adult patients.