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Moving beyond 3 plus 3: design innovations for precision oncology and implications for decision-makers

Brian Hobbs, Associate Professor, Dell Medical School University of Texas
August 2, 2023 (SDP Invited Talk)

Abstract: Over the years, the FDA has established several pathways to speed up the review process for emerging therapies for serious conditions with unmet medical need. One such mechanism is Accelerated Approval. It is based on surrogate endpoints, where efficacy is often quicker to establish. The changes in the approval pathway prompted innovations in trial design with master protocol and seamless designs. Immune checkpoint inhibitors (ICIs) have yielded promising therapies for patients experiencing refractory cancers. Trials evaluating ICIs made extensive use of phase Ib, enrolling hundreds and even more than one thousand patients into dose expansion cohorts following dose-escalation spanning multiple tumor types. This represents a departure from conventional drug development strategies, for which dose expansion cohorts were used in roughly 25% of phase trials.

Moreover, in 2021 two drugs, Atezolizumab and Durvalumab, were voluntarily withdrawn from accelerated approvals for PD-L1 inhibition in advanced or metastatic bladder cancer.

 This presentation considers the statistical implications of expansive, uncontrolled early phase trials as well as the challenges to leveraging real-world evidence in this setting. The design of these early clinical trials has direct implications to the future success of a program. Thoughtful and appropriate statistical designs can potentially decrease later stage clinical failures, therefore impacting the overall clinical development of a program through approval.

Click on the file below to hear a sample of the presentation.  

 Click here for access to the full video.

SDP membership is required for access to this webinar.

 Keywords: analysis and modeling anamod, risk and uncertainty riskunc, medical decisions meddec, statistics,