The Mathematical Quest of Administering the Right Dose/schedule of the Right Drug to the Right Patient in BioOncology

Deliberate data-driven development of BioOncology molecules is by necessity a front-loaded process characterized by evolution in our understanding of the link between exposure/tumor response/treatment outcome. This is facilitated by a sequential development process - early to late research followed by sequential clinical trials to elucidate the safety and efficacy of new molecular entities. With the advent of targeted cancer therapies, the ability to administer the right dose/schedule of the right drug to the right patient becomes an attainable goal. A novel Translational BioOncology platform for projecting target clinical efficacious doses for cytotoxic/cytostatic agents based on linking mouse xenograft data to clinical objective responses has been developed. These methods allow for the estimation of an optimal clinical dose/regimen and definition of the most efficient Phase I dose escalation scheme to reduce the number of patients dosed at suboptimal levels while rapidly approaching the projected target therapeutic doses without risking the safety of patients. This approach has been used successfully to support efficacious dose projections in IND submissions, enabled informed Go/No go decision-making, and provided justification for novel clinical trial design. Further application of these modeling and simulation approaches will also prove their utility in combination therapies and treatment optimization.

Nelson (Shasha) Jumbe, Genentech

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