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We propose a flexible design for the identification of optimal dosecombinations in dual-agent dose-finding clinical trials. The design is calledAAA, standing for three adaptations: adaptive model selection, adaptive doseinsertion, and adaptive cohort divi- sion. The adaptations highlight the needand opportunity for innovation for dual-agent dose finding, and are supportedby the numerical results presented in the proposed simulation studies. To ourknowledge, this is the first design that allows for all three adaptations atthe same time. We find that AAA improves the statistical inference, enhancesthe chance of finding the optimal dose combinations, and shortens the trialduration. A clinical trial is being planned to apply the AAA design.

AAA: Triple-adaptive Bayesian designs for the identification of optimal dose combinations in dual-agent dose-finding trials