Dose Optimization
Chair: Jingjing Schneider (BeiGene)
Vice Chair: Shibing Deng (Pfizer)
Speaker: Naitee Ting (Boehringer Ingelheim)
Title: Proof of Concept in a Phase II Trial Combined with Dose Ranging
Abstract: Traditional Phase II clinical development of new drugs treating chronic diseases separates one study for proof of concept (PoC), and other studies for dose ranging purposes. With the availability of ordinal linear contrast test (OLCT) and MCPMod, most recent Phase II combines PoC and dose ranging into a single trial. Under this circumstance, the PoC step can be considered from various angles. Accordingly, sample size based on various scenarios can reflect different considerations. Given a fixed total sample size of 300, this presentation discusses simulation results of PoC with different number of dose groups, and various sample size allocation strategies.
Speaker: Hongqian Wu (BeiGene)
Title: Oncology Dose Selection Conundrum: can we pick the winner in a randomized dose ranging study?
Abstract: The randomized dose-ranging study, although commonly done in therapeutic areas other than oncology, is usually not implemented in oncology drug development. With the initiative “Project Optimus” launched by the FDA Oncology Center of Excellence to reform the dose optimization and dose selection paradigm in oncology, it is suggested to evaluate at least two doses of cancer treatment in a randomized manner by FDA and other researchers. The background and motivation of this suggestion together with recent and current randomized dose-ranging studies are reviewed. We then discuss multiple relevant aspects of a randomized dose selection design in oncology.
Speaker: Jun Zhang (BeiGene)
Title: From MTD to Optimized Dose Selection in Oncology Drug Development
Abstract: Historically, a maximum tolerated dose (MTD) based dose selection diagram has been widely used. The decision to select the highest tolerable dose evaluated for pivotal clinical studies is a carryover from the cytotoxic drug development era. The underlying belief is that higher drug doses will have better therapeutic activity. However, for new oncology drugs (e.g., targeted therapies or I/O), giving excess drug over a target may not enhance antitumor activity and may add to DLTs or long-term tolerability issues after multiple cycles. Project Optimus is a recent initiative by US FDA Oncology Center of Excellence that reforms the dose optimization and dose selection paradigm in Oncology drug development in the new era of blooming targeted and immuno therapies. There has been a shift of focus from Maximum Tolerated Dose identification to dose / dosing regimen optimization in the Oncology dose finding studies. In this talk, case studies under various situations will be shared. The challenges and proposed designs will be discussed.
