Abstract A125: External Control Arms: a vital strategy to create high quality scientific evidence with patient centric trial design for pancreatic cancer trials in light of introduction of highly effective targeted therapies
Ruthie DaviAbstract
ABSTRACT:
AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development
Background:
The evolution of targeted therapies in pancreatic ductal adenocarcinoma (PDAC) may pose challenges for future clinical research. Assigning patients to standard-of-care chemotherapies in randomized controlled trials (RCTs) may become ethically complex and practically infeasible, slowing drug development for this high-unmet-need population, if targeted therapies are available.
Objective:
This session will demonstrate how external control arms (ECAs), using patient-level data from prior trials or real-world sources, can:1. Create more patient-centric, operationally-feasible, late-phase RCTs that increase the chances of trial patients being randomized to new therapies while maintaining scientific credibility.2. Provide important contextual evidence to improve scientific certainty in early-phase trials.Key Use Cases Include:1. A multi-stakeholder validation pilot with Friends of Cancer Research to determine if an ECA can replicate overall survival (OS) outcomes from a historical PDAC trial’s randomized control arm.2. Contextualization of an early-phase, uncontrolled trial’s efficacy outcomes to inform internal decision-making and generate early comparative evidence.
Discussion:
We present findings evaluating ECA alignment to a randomized control in a Friends of Cancer Research pilot. Results highlight that with high-quality data and careful propensity score matching or weighting, external controls can replicate a randomized control. We also present the results of an ECA used to contextualize efficacy outcomes in a phase 1b uncontrolled trial.
Conclusion:
External controls represent a necessary shift in PDAC research. By providing alternatives to 1:1 randomized trials and gaining more insights from early-phase, single-arm trials, ECAs facilitate scientific progress and reduce patient burden. The work presented here underscores that with rigorous methodology and fit-for-purpose data, adopting these innovative designs is essential for maintaining momentum in pancreatic cancer research, ultimately delivering life-saving treatments faster.
Disclosure:
The text for this abstract was generated with the assistance of an AI tool.
Citation Format:
Ruthie Davi. External Control Arms: a vital strategy to create high quality scientific evidence with patient centric trial design for pancreatic cancer trials in light of introduction of highly effective targeted therapies [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A125.