Platform, Basket, Umbrella Trials in Precision Medicine

Basket Trials

Basket trials assess the safety and efficacy of a single targeted therapy across multiple diseases or disease sub-groups that share a common biomarker. By grouping these patients into one “basket,” researchers can evaluate how a treatment performs across different conditions simultaneously.

• Single therapy across multiple cancer types
• Patients grouped by shared biomarkers
• Data sharing across cohorts
• Typically single-arm, non-randomized
• Early-phase (Phase I/II) exploratory
• Identifies early proof-of-concept signals

Basket Trial as an Accelerated Pathway to Proof-of-Concept

A real-world example highlights how basket trials can accelerate development. Precision for Medicine collaborated with a sponsor to design an adaptive basket trial that could explore multiple tumor types simultaneously. The goal was to create a faster pathway to proof-of-concept while maintaining scientific rigor.

Despite its innovative approach, the trial faced several operational and scientific challenges, including limited patient availability, non-standard biomarker usage, and complex screening requirements. Site teams also needed the expertise to manage advanced genomic data, adding to operational complexity.

Through careful planning and execution, the trial successfully scaled and evolved over time.

• Target population represented only 2%–8% of all solid tumors
• Required non-standard biomarker testing and complex screening processes
• Site staff needed capabilities to handle advanced genomic data
• Expanded to 20 tumor-specific cohorts
• 7 treatment approaches were discontinued based on interim data
• Continued to add new cohorts and explore combination therapies
• Grew from 100 patients across 6 sites to 250+ patients across ~50 global sites

Umbrella Trials

Umbrella trials evaluate one or more targeted therapies within a single disease, such as a specific type of cancer. Patients are first screened for different biomarkers or genetic characteristics and then assigned to treatment groups (sub-studies) based on those profiles. This design allows researchers to test multiple hypotheses within one trial, making it more efficient than running separate studies.

• Focus on a single disease type
• Patients are grouped based on biomarkers or molecular profiles
• Test multiple therapies simultaneously
• Can be randomized or non-randomized
• May include a shared/common control arm
• Enable testing of multiple hypotheses in one trial
• Can reduce overall patient numbers and trial costs

Platform Trials

Platform trials are flexible, ongoing studies designed to evaluate multiple treatments over time within the same disease area. Unlike traditional trials with a fixed end, platform trials are “open-ended,” meaning new treatment arms can be added and ineffective ones can be removed as the study progresses.

• Focus on a single disease or condition
• Open-ended design with no fixed end date
• Allow adding or dropping treatment arms over time
• Can be randomized or non-randomized (often randomized)
• Used across different phases of clinical research
• Improve efficiency through adaptive design

Common Adaptive Design Elements:

• Group sequential design: Stop treatment arms early for futility, safety, or success
• Multi-arm, multi-stage (MAMS): Add new treatments during the trial
• Sample size re-estimation: Adjust patient numbers to maintain statistical power
• Population enrichment: Focus on patients most likely to benefit
• Adaptive randomization/dose adjustment: Allocate more patients to promising treatments

Master Protocols and Their Potential in IBD Clinical Trials

Master protocols offer a promising way to improve the clinical trial landscape in inflammatory bowel disease (IBD). By allowing multiple treatments to be studied under a single trial framework, these designs can significantly reduce the number of patients required especially through the use of shared control groups.

With a growing pipeline of new therapies in IBD, testing one drug at a time using traditional trial designs is no longer practical. Master protocols enable multiple treatments to be evaluated simultaneously, making them especially valuable in early-stage development. They are particularly effective at the proof-of-concept or Phase II stage, where recruitment is difficult and faster decision-making (go/no-go) is critical.

• Reduce overall sample size through shared control groups
• Minimize patient exposure to placebo
• Address declining recruitment rates in IBD trials
• Enable simultaneous testing of multiple therapies
• Support faster go/no-go decision-making
• Particularly useful in proof-of-concept and Phase II trials
• Offer a more patient-centric and adaptive approach

Challenges with Master Protocol–Based Trials

• Represent a significant shift from traditional trial designs
• Limited experience and familiarity among sponsors and trialists
• Require advanced planning and coordination
• Increased regulatory scrutiny and detailed review
• Need clear justification of:
• Statistical validity and error control
• Rules for stopping or modifying treatment arms
• Simulation-based design characteristics