With the rise of targeted and immunotherapies, we have recently seen a shift away from finding a drug’s maximum tolerated dose (MTD) in Phase II dose-finding studies and toward identifying the optimal biological dose (OBD) — the dose that optimally balances safety, tolerability, and early efficacy. A new method, PKBOIN-12, extends the BOIN12 framework to integrate Pharmacokinetic (PK) parameters to refine the dose-finding and final OBD selection.

Here, we discuss PKBOIN-12, recent regulatory shifts regarding dose finding, including the FDA’s Project Optimus, and Cytel’s East Horizon™ dose-finding module.

What is PKBOIN-12?

PKBOIN-12, developed by Dr. Hao Sun of Bristol Myers Squibb and Tu Jieqi of the University of Illinois Chicago, is an innovative dose-finding method that enhances the established BOIN12 algorithm by incorporating Pharmacokinetic (PK) information into the Optimal Biological Dose (OBD) determination process. In recent years, particularly with the rise of targeted and immunotherapies, the focus in early-phase dose-finding studies has shifted away from finding the Maximum Tolerated Dose (MTD) and toward identifying the OBD, the dose that optimally balances safety, tolerability, and early efficacy.

BOIN12 is one such method that assesses both safety and efficacy, but, like many dose-finding designs, it typically does not formally use auxiliary data. Researchers routinely collect PK measurements in order to characterize drug exposure associated with the various tested dose levels, but these are not usually incorporated into the risk-benefit analysis when designing clinical trials. PKBOIN-12 addresses this by extending the BOIN-12 framework to integrate collected PK data to refine the dose-finding and final OBD selection.

Indeed, simulation results comparing PKBOIN-12 and BOIN-12 demonstrate that the former more effectively identified the OBD and allocated a greater proportion of patients to that optimal dose.

Project Optimus: A regulatory shift toward the OBD

In addition to the general industry trend in collecting and considering a broader set of data in early-phase dose-finding oncology studies, we have seen a real shift in regulatory interest in this area, encapsulated in the FDA’s Project Optimus.

In a previous blog post, James Matcham and Michael Fossler highlight how a recognition of the changing nature of oncology therapies — away from chemotherapies and towards more advanced biologics — necessitated a change in how these products are developed and assessed for efficacy and safety.

Project Optimus posits that the dose-finding paradigm must shift away from safety and tolerability alone, and towards incorporating efficacy considerations at this stage. An ideal dose-finding study under the Project Optimus lens emphasizes the determination of a dose range that does not focus on the MTD, but rather the OBD, or the dose range that considers efficacy, tolerability, safety, and pharmacokinetics.

PKBOIN12 is therefore well-suited to meet the challenges presented by Project Optimus and is indeed at the forefront of both industry trends and regulatory expectations.

Dose finding with the East Horizon™ platform

Cytel’s software development teams will soon be launching the dose-finding module, the sixth installation of the East Horizon platform. This module completes an almost two-year journey of migrating Cytel’s flagship software heritage, East, into a cloud-native, modern, and updated East Horizon platform. Over these months, our teams worked tirelessly to select from our wide repertoire of software solutions, those features, methods, and tests most relevant to our user base, and thoughtfully curated additional frequentist and Bayesian methods that are completely new for Cytel software. One such method is the new PKBOIN-12 dose-finding method.

Interested in learning more?

On November 18, 2025, Cytel will host Dr. Hao Sun for a webinar to discuss this new method in depth, and to highlight the technical as well as tactical aspects of implementing this method. Register today and join us for a fascinating conversation:

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