Science

Aug 3, 2025, 11:23

Daniel Weiss: Optimizing Dosage Selection Strategies in Oncology Clinical Trials

Daniel Weiss, Consultant of Drug Development at ECD Life Sciences, shared a post on LinkedIn about recent paper by Laura Levit et al., published in Journal of Clinical Oncology.

“Optimizing Dosage Selection Strategies in Oncology Clinical Trials

The field of oncology drug development is undergoing a fundamental transformation. The newly published American Society of Clinical Oncology (ASCO) Special Article, ‘Totality of the Evidence: Optimizing Dosage Selection Strategies in Oncology,’ underscores the FDA’s shift. Sponsors are now expected to optimize dosing—prior to approval—using the totality of evidence and reflecting on the patient experience.

The authors (Laura Levit, Mark Ratain, Elizabeth Garrett-Mayer, PhD, FSCT, Nam Atiqur Rahman, and R. Donald Harvey, PharmD, FCCP, FHOPA, FASCO) reflect on five concrete actions for project teams, clinical leaders, and sponsors to operationalize this paradigm:

Expand safety and tolerability data collection

Move beyond severe toxicities in cycle one. Integrate chronic, lower-grade adverse events and patient-reported outcomes (PROs) into phase I and II studies to ensure dose decisions truly reflect the lived patient experience—not just short-term snapshots.

Tailor development to the molecule and population

Targeted therapies and immuno-oncology agents often demonstrate wide therapeutic indices and plateauing dose-response curves. Don’t default to ‘more is better’—challenge old assumptions and leverage pharmacology to set rational starting and registration doses.

Adopt modern, randomized trial designs

Transition from single-arm RP2D trials to model-based and randomized, dose-ranging phase II designs. These approaches yield richer data and more meaningful benefit–risk assessments, supporting robust regulatory action and clinical guidance.

Broaden eligibility criteria

Stop excluding large swaths of real-world patients. Inclusive criteria improve recruitment, expand generalizability, and democratize access to innovative therapies.

Deepen and integrate clinical pharmacology analyses

Build robust pop-PK/PD models from the outset. Consider all sources of variability—demographic, genetic, environmental. Leverage pharmacodynamic and blood-based biomarkers to enable smarter, more individualized dosing.

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Title: Totality of the Evidence: Optimizing Dosage Selection Strategies in Oncology

Authors: Laura Levit, Mark Ratain, Elizabeth Garrett-Mayer, PhD, FSCT, Nam Atiqur Rahman, and R. Donald Harvey

Read The Full Article at Journal of Clinical Oncology.

Daniel Weiss: Optimizing Dosage Selection Strategies in Oncology Clinical Trials