Early Phase Oncology design in light of ProjectOptimus
The US-FDA’s Project Optimus has reshaped the early phase development pathway for Oncology therapies, regardless of where the studies are conducted. The Maximum Tolerated Dose is no longer the sole basis for choosing a dose, and a randomized dose optimization phase is now required. This dose optimization phase in turn, then changes the optimal design of the escalation phase – choosing between 3+3, BOIN, CRM or mTPI is no longer critical. In contrast, details that apply similarly to all designs do become critical. This includes the use of accelerated titration, choice of target toxicity, capon patients at each dose level, whether to re-test a dose from which you previously de-escalated, and judicious use of backfill.
During randomized doseoptimization, solutions that keep this phase flexible, such as multiple interimanalyses, parallel escalation or further expansion in the event of exceptionalefficacy enable this phase to be used as the primary tool for dose selection. Counter-intuitively, rather than increasing the size and complexity of oncologyprograms, the randomized dose-optimization phase creates opportunities forprograms to have lower sample sizes, and run quicker than traditional single-doseprograms, as well as opening new pathways for an early claim of efficacy. For example, randomized studies provide a valid basis for the use ofProgression Free Survival and Overall Survival as endpoints in addition toOverall Response Rate. To leverage the potential of these designs,studies need to be analyzed with appropriate statistical models.
Speaker: Dr William Reece, Biostatistics Director at Fortrea
Location: Virtual – please contact apbgsteering@gmail.com for meeting link
