February 24, 2019

COMBO

Dual-agent Drug Combination Dose Finding Design


COMBO can be used for the identification of the combination-dose MTD and optimal dose combinations in dual-agent dose-finding for phase I or phase I/II clinical trials of combination drug development.

Through customization of different functional modules, the COMBO design is applicable to the dose finding for cytotoxic drug development (only considering dose toxicity relationship) as well as biological or immunological drug development (considering both dose toxicity relationship and dose efficacy relationship). In addition, COMBO allows for other adaptive scheme, such as adaptive dose insertion and patients enrollment in parallel cohorts in the AAA design (JRSSC; Lyu et al., 2018)

Benefits

  1. It can incorporate the dose efficacy – dose-toxicity relationship in the dose finding to find out the optimal biological dose combination while meeting the demand of safety and reliability. This design is typically tailored for non-cytotoxic drugs, such as biological and immune therapies.
  2. It allows new doses to be adaptively inserted during the trial, which reduces the difficulty of presetting the dose range, number of doses and each dose regimen, and benefits the enrolled patients by assigning optimal doses to them.
  3. The patients are allowed to be enrolled simultaneously in parallel cohorts and allocated on multiple doses, which shortens the trial duration and protects patients safety.