Advancement in bioscience and technology has yielded a number of new efficacy endpoints for phase 2 proof-of-concept (POC) trials to consider. In this presentation, we will provide practical measures for evaluation of such endpoints. We will further provide optimal design strategies for POC trials that include Go-No Go decision criteria for initiation of phase 3 and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology POC trials are used for illustration purpose, the same idea also applies to similar situations in other therapeutic areas or in early stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.