Challenge
A start-up biotechnology company was developing a new oncology therapeutic for the treatment of advanced solid tumors. The product consists of four FDA-approved and well-tolerated supplements, all of which have anti-cancer activity. Each of these supplements attacks one of the hallmarks of cancer – angiogenesis, evasion of apoptosis, avoidance of immune detection, and altered metabolism – that support tumor growth. The company was looking for an oncology drug development consultant to help with an investigational new drug (IND) application to the FDA for a Phase 1 trial.
Solution
Our experienced oncology drug development consultant, supported the client as a part-time Chief Medical Officer to develop an IND package for the initial FDA application.
All four compounds in the regimen were already known to be safe, both individually and sometimes in 2-drug combinations. They are bioavailable and have been widely used for years. He therefore sought a trial design that would assess the safety of this particular combination regimen in the most efficient manner possible. With four components involved, a standard Phase 1 drug escalation study would have been unwieldy and prohibitively complex. Based on conversations with former FDA officials, he designed a dose de-escalation trial. In this unusual strategy, an initial block of 10 patients would be treated with the combination therapy, and if the conservative safety threshold was breached then the study would revert to escalating doses of individual components. If the combination was safe at the chosen dose for each drug, however, then the overall cost and duration of the trial would be substantially smaller than for a conventional approach. He allowed for up to 20% of these patients to have a dose-limiting toxicity, a level that he thought would be sufficient to adequately test the safety of the therapy.
Our consultant successfully vetted this trial design in a pre-IND meeting. He then put together an IND package that was subsequently approved: the Phase 1 trial is slated to begin in 2017. Our consultant has stayed on in an advisory role to provide continuous support.
Our consultant’s expertise and experience, including sound relationships with FDA staff, was critical to finding the most cost-effective and time-efficient trial design.