Case Study: Biomarker-Driven Enrollment Using Notch Mutation Targeting

Written by Alexis Hobbins-White | Oct 7, 2025 1:21:01 PM

Biomarker-driven trials are transforming oncology research, enabling targeted therapies for genetically defined populations. Precision partnered with a biotech sponsor developing a Notch-targeted therapy to manage two concurrent Phase 2 trials—one in Adenoid Cystic Carcinoma (ACC) and one in triple-negative breast cancer (TNBC).

Study Type	Phase 2
Therapeutic Area	Oncology
Indication	ACC with activating Notch mutations
Geography	US, Canada, EU
Sites	24 total (17 US/Canada, 7 EU)
Precision’s Role	End-to-end operational support including site selection, biomarker strategy, NGS coordination, and regulatory guidance
Key Challenges	Biomarker-driven eligibility, NGS coordination, regulatory risk determination, and minimizing screen failures

This case study focuses on the ACC trial, which required identifying patients with activating Notch mutations through next-generation sequencing (NGS). The study was split into two parts:

Part 1: 35+ patients enrolled over 12 months
Part 2: 50+ additional patients targeted over the following 12 months

Strategic Design and Site Selection

Precision’s success began with identifying the right sites—those capable of performing NGS testing either internally or through a vendor. This capability was critical to minimizing screen failures and accelerating enrollment.

Key considerations included:

Targeting Notch 1–4 mutations
Implementing pre-screening informed consent (ICF) to reduce screen failures
Navigating Significant Risk Determination as part of regulatory submission
Sponsor review and approval of NGS results prior to patient enrollment

Precision worked closely with sites to coordinate sample collection and pre-screening logistics, including the use of standardized kits and early activation of the NGS vendor.

Lessons Learned and Operational Wins

Despite the complexity of biomarker-driven enrollment, the ACC trial exceeded expectations:

Enrollment rates were better than anticipated, thanks to strategic site selection and pre-screening
NGS testing was streamlined, with vendor activation completed upfront
Site coordination was optimized, enabling consistent sample handling and data flow
Regulatory alignment was achieved early, avoiding delays in patient entry

Precision’s proactive approach ensured that biomarker testing did not become a bottleneck, but rather a catalyst for efficient enrollment.

Precision’s Path to Biomarker-Driven Enrollment in Rare Oncology

The ACC trial demonstrated that biomarker-driven studies can succeed with the right infrastructure, planning, and site partnerships. Precision’s experience in coordinating NGS workflows, managing regulatory complexity, and supporting site operations was instrumental in achieving strong enrollment and data quality.

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