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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
EMPIRE (NSABP FC-13): a biomarker-driven phase II platform trial evaluating cemiplimab-based immunotherapy in
Anwaar Saeed1,2, Greg Yothers3, Shannon L Puhalla1,2
1NSABP Foundation, Inc., Pittsburgh, PA, USA.
Abstract:
Microsatellite-stable (MSS) colorectal cancer (CRC), which accounts for approximately 85% of cases annually, has demonstrated limited responsiveness to immune checkpoint blockade in the metastatic setting. Circulating tumor DNA (ctDNA) enables sensitive detection of minimal residual disease (MRD) following curative-intent therapy and identifies patients at high risk of recurrence who may benefit from additional treatment. The EMPIRE (NSABP FC-13) study is a multicenter, open-label, randomized phase II platform trial evaluating cemiplimab-based immunotherapy in patients with MSS CRC and ctDNA-defined MRD after definitive surgery and chemotherapy. Eligible patients have postoperative ctDNA positivity in the absence of radiographic recurrence and are allocated to one of three treatment arms: cemiplimab monotherapy; cemiplimab plus fianlimab (a lymphocyte activation gene-3 inhibitor); or cemiplimab plus REGN7075 (an EGFR×CD28 costimulatory bispecific antibody). The primary endpoint is ctDNA clearance at 12 weeks assessed by tumor-informed assay, with secondary endpoints including recurrence-free survival, safety and tolerability, longitudinal ctDNA kinetics, and patterns of recurrence. Arms 2 and 3 use single-stage phase II designs, whereas Arm 1 follows a Simon two-stage design with early futility stopping. The study integrates comprehensive correlative analyses to characterize mechanisms of response and resistance.Clinical trial registration: The http://www.clinicaltrials.gov identifier is NCT07058012.
Insights
This study investigates novel immunotherapies for microsatellite-stable colorectal cancer (MSS CRC) with minimal residual disease (MRD) detected by circulating tumor DNA (ctDNA). It aims to improve treatment outcomes for high-risk patients post-surgery and chemotherapy.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- Microsatellite-stable colorectal cancer (MSS CRC) shows poor response to current immunotherapies.
- Circulating tumor DNA (ctDNA) detects minimal residual disease (MRD) after treatment, identifying high-risk patients.
- Novel therapeutic strategies are needed for MSS CRC patients with ctDNA-defined MRD.
Purpose of the Study:
- To evaluate cemiplimab-based immunotherapy in patients with MSS CRC and ctDNA-defined MRD.
- To assess the efficacy of cemiplimab monotherapy, cemiplimab plus fianlimab, and cemiplimab plus REGN7075.
- To identify patients who may benefit from adjuvant immunotherapy after surgery and chemotherapy.
Main Methods:
- A multicenter, open-label, randomized phase II platform trial (EMPIRE/NSABP FC-13).
- Patients with MSS CRC and postoperative ctDNA positivity (no radiographic recurrence) were enrolled.
- Three treatment arms: cemiplimab alone, cemiplimab + fianlimab, or cemiplimab + REGN7075.
Main Results:
- Primary endpoint: ctDNA clearance at 12 weeks via tumor-informed assay.
- Secondary endpoints: recurrence-free survival, safety, ctDNA kinetics, and recurrence patterns.
- Correlative analyses will explore mechanisms of response and resistance.
Conclusions:
- The study will provide critical data on the efficacy of novel immunotherapy combinations for MSS CRC with MRD.
- Findings may lead to new treatment paradigms for high-risk MSS CRC patients.
- Understanding response and resistance mechanisms is key for future therapeutic development.
