Horizon Two: HR NDMM (MMRC-100)

The master protocol has broad scope and substantial flexibility, allowing each investigational arm within the platform to have its own design. The master protocol specifies general principles but the analysis plan for each investigational arm will be specified in its appendix. Details outlined in each investigational arm's appendix will include any co-primary endpoints (if applicable), the comparator arm, sample size and justification, inclusion of a safety run-in (if required), and any potential adaptations within the appendix. Accrual to an investigational arm will terminate in accord with its appendix. As an adaptive platform trial, MMRC Horizon Two will evaluate multiple investigational arms against common controls. It is expected that the common controls may vary over time as standard of care therapy evolves. An initial common control arm will be specified in the control arm appendix. Changes in the common controls will be made through amendments to this appendix. All patients will be randomized to an arm in the study. The default for the platform will be equal randomization to all arms that a patient is eligible. However, when there are more than two investigational arms and response adaptive randomization is deemed beneficial, it may be implemented in the trial. Participants will be on study for 5 years from the date of randomization, inclusive of treatment and follow-up periods. Specifics on treatment duration and duration of follow up will be included in the respective arm appendix.