Master Protocols

Organizers: Miaomiao Ge (Boehringer-Ingelheim), Freda Cooner (Amgen), Anastasia Ivanova (UNC)
Chair: Miaomiao Ge (Boehringer-Ingelheim)
Vice Chair: Freda Cooner (Amgen)

Sheng Qiu (Boehringer-Ingelheim)
Sirisha Mushti (FDA)
Joseph Marion (Berry Consultants)
Anastasia Ivanova (UNC)


Title: Master protocol – Pains and Gains
Speaker: Sheng Qiu (Boehringer-Ingelheim)

One of the biggest challenges that the pharmaceutical industry has always been facing is the cost of drug development. As an efficient and innovative method to run clinical trials across diseases and/or across drugs, master protocols have been carried out in many therapeutic areas. With its advantage of potentially reducing the sample size, reducing screen failure rate, being available to different patient cohorts and with more treatment options etc., there are certainly pain points when conducting such a trial, e.g., frequent update of the protocol, complicated treatment allocation, lengthy discussion with different stakeholders. In this presentation, I would like to share my experience running the first oncology master trial at Boehringer Ingelheim, and exploration of multiple Bayesian Hierarchical Modelling (BHM) approaches for master protocol design.

Title: Master protocols in Action – Applications in Oncology at FDA
Speaker: Sirisha Mushti (FDA)

The 21st Century Cures Act has helped accelerate the drug development process and bring new innovations and advances to patients in a faster and more efficient way. The new innovative designs like umbrella, basket and platform trials also shares this mission and are accomplished via master protocols.
In recent times, the trials implemented through master protocols has shown to be out-performing compared to the traditional drug development process that relies upon the ideology of one drug, one trial, and one phase at a time. There has been growing experience and interest in the use of master protocol designs within oncology. FDA has published a draft guidance on master protocols and also issued an article discussing modernization of clinical trials with master protocols. In this presentation, I will briefly present the concept of master protocols, regulatory review process of the master protocols, list few pros and cons of master protocols, things to consider when designing master protocols and the challenges encountered during the review process, and present few examples of approvals in oncology based on master protocols.

Title: Sharing is Caring (In Platform Trials)
Speaker: Joseph Marion (Berry Consultants)

Platform trials test multiple therapies within a single clinical trial infrastructure. This integrated approach can also be used to assess the effect of those therapies across patient subgroups. The ongoing I-SPY 2 trial, which was one of the first platform trials, estimates the effect of treatment on subgroups identified by patient biomarker values such as HER2 status. Other platform trials incorporating subgroups include GBM Agile, which uses line of therapy and methylation status, and the COVID-19 mpRCT, which analyzes treatment effects according to disease severity and D-Dimer levels. The identification of treatment-responsive subgroups is central to the platform trial mission of providing individualized treatments to patients.

In this talk, we discuss platform trial design in a setting where subgroups are not discrete but instead characterized by a continuous predictive measure or biomarker. This approach leverages a richer source of information and may improve our ability to identify targeted therapy options for patients. The design uses non-linear regression to model the relationship between the continuous measure and the treatment effect. Then, we use this analysis to establish a signature, which is a biomarker-based subgroup of patients that are more likely to benefit from treatment. We discuss aspects of this approach that are unique to the platform trial setting, such as developing drug-specific signatures, using the predictive measure for adaptive randomization, and re-enrolling successful interventions to the platform for signature confirmation.

Title: Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE)
Speaker: Anastasia Ivanova (UNC)

The NIH PrecISE program was established to conduct Phase 2 type proof-of-concept studies aimed at testing interventions in biomarker-defined subgroups of patients with severe asthma.  The PrecISE Network clinical trial uses an adaptive platform design conducted under a single Master Protocol to accommodate evaluation of multiple simultaneous and/or successive interventions in patients with severe asthma. We discuss several aspects of the PrecISE study design.