Laiya-One: A 21st Century Phase 1 Trial Design Suite

A proposal to transform phase 1 oncology trials at company xyz

Laiya Consulting, Inc.
September 28, 2019

Purpose: To promote the use of a novel phase 1 trial design suite that tailors to the modern needs of phase 1 clinical trials in oncology.

Introduction: Based on a set of innovative statistical designs and approaches, Laiya proposes a suite of solutions to transform phase 1 trials for new drug development (Figure 1). The solutions aim to short the trial duration, reduce sample size and cost, but still maintain safety and sufficient power. Innovatively, we also provide decision tools that help control the type I error of critical decision making to reduce the failure rates of phase 2 and 3 trials.


Figure 1: Laiya One — A 21st Century Phase 1 Trial Design Suit

How/Where can Laiya-One Help During Phase 1 Development

Laiya-One provides end-to-end services on the entire phase 1 trial and drug develop (Figure 2)


Figure 2 Laiya-One main functions for the phase 1 trial and drug development

Available Designs and Benefits:
The suite includes four novel designs.

  1. The i3+3 design (and extensions). It is a cohort-based dose-finding design suitable for standard DLT-based phase 1a trials. Below are some notable features and benefits.
    1. i3+3 has a much higher chance of identifying the true MTD
    2. i3+3 has proven a success at the US and Chinese IND applications
    3. i3+3 is operationally as simple as the 3+3 design
    4. i3+3 variations (mi3+3 and ci3+3) allows biomarker subgroups and combo dose finding
  1. The PoD-TPI design. It is a break-through type of design allowing faster patient enrollment for standard DLT-based phase 1a trials. Below are some notable features and benefits. It is the first type of dose-finding design that offers the following features and benefits.
    1. PoD-TPI quantifies the risk of dose-finding decisions – this is critical if we want to speed up enrollment
    2. PoD-TPI accelerates patient enrollment while maintaining the safety
    3. PoD-TPI assesses existing designs and their risks – important to benchmark future designs
  1. The MUCE design. It is a novel design and decision-making tool allowing a more efficient sample size/power/decision-making process for phase 1b multiple expansion cohorts studies.
    1. MUCE can accommodate multiple doses, schedules, combinations, and indications to be included in a single study.
    2. MUCE results in a smaller sample size (as much as half) than the standard designs, such as the Simon’s two-stage design
    3. MUCE has a build-in function to control the overall type I error rate – to reduce the false selection of indication and dose for phase 2 trials

Examples:

The i3+3 design and its alternatives

  1. Laiya has helped a US company to secure an IND approval including a mi3+3 design is used to help guide all comers and a biomarker-positive subpopulation goes through dose-finding states simultaneously. This greatly reduced the time and cost since, without the mi3+3 design, two sequential dose-finding trials will be needed, one for the all-comers and one for the subpopulation.
  2. Laiya has helped multiple Chinese and US companies designs seamless phase 1a dose-escalation and multiple expansion cohort trials. The dose-escalation part is based on the i3+3 design and the expansion cohort part is based on the MUCE design. This helps speed up the drug development with a single protocol, and the MUCE design results in a 10-40% sample size reduction.
  3. Laiya has helped with investigator-initiated trials (IITs) in which the MUCE design is applied to multi-arm phase 2 basket trials. In a three-arm trial targeting different lines of therapy, the MUCE design results in a 50% sample size reduction when compared to Simon’s two-stage design.

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