  We consider a modified Ci3+3 (MCi3+3) design for dual-agent dose-finding
trials in which both agents are tested on multiple doses. This usually happens
when the agents are novel therapies. The MCi3+3 design offers a two-stage or
three-stage version, depending on the practical need. The first stage begins
with single-agent dose escalation, the second stage launches a model-free
combination dose finding for both agents, and optionally, the third stage
follows with a model-based design. MCi3+3 aims to maintain a relatively simple
framework to facilitate practical application, while also address challenges
that are unique to novel-novel combination dose finding. Through simulations,
we demonstrate that the MCi3+3 design adeptly manages various toxicity
scenarios. It exhibits operational characteristics on par with other
combination designs, while offering an enhanced safety profile. The design is
motivated and tested for a real-life clinical trial.
