NSABP FC-13 (EMPIRE): A phase II platform study of cemiplimab monotherapy or cemiplimab-based combinations in patients with colorectal cancer and minimal residual disease (MRD) after definitive therapy.

Abstract

TPS3685 Background: Patients with microsatellite-stable (MSS) colorectal cancer (CRC) who are ctDNA-positive following surgery and chemotherapy have a high risk of recurrence and limited treatment options. Immune checkpoint blockade with PD-1/PD-L1 inhibitors, alone or with other immune modulators, may be most effective in early-stage disease or in patients without liver metastases. However, no approved therapies currently exist for patients with MSS CRC and ctDNA-positivity after curative-intent therapy, making this high-risk population an area of critical unmet need and opportunity for new drug development. NSABP FC-13 (EMPIRE) is a Phase II platform trial evaluating cemiplimab alone or in combination with novel agents in this high-risk MRD setting, wherein ctDNA clearance serves as an early surrogate marker of therapeutic activity. Methods: This multicenter Phase II platform study randomizes patients with MSS stage II–III or oligometastatic stage IV CRC who are ctDNA-positive within 12 weeks of completing definitive therapy (surgery ± chemotherapy/chemoradiotherapy) to one of three arms: (1) Cemiplimab 350 mg IV q3w × 1 year; (2) Cemiplimab 350 mg + fianlimab 1600 mg IV q3w × 1 year; (3) Cemiplimab 350 mg + REGN7075 2700 mg IV q3w × 1 year. Eligibility includes ECOG 0–1, adequate organ function, and absence of radiographic recurrence at enrollment. Assessments include serial tumor-informed ctDNA testing (Signatera, Natera, Inc.), imaging, labs, and safety monitoring. The primary endpoint is ctDNA clearance at 12 weeks without radiographic recurrence. Secondary endpoints include recurrence-free survival (RFS), safety, ctDNA kinetics, and patterns of recurrence. Statistical design: Arm 1 follows a Simon two-stage design with up to 33 patients (α=0.047, power=0.80), and Arms 2 & 3 enroll up to 23 patients each (single-stage; α=0.05, power=0.78). Status: Enrollment began in September 2025 across NSABP Foundation sites and is ongoing. Clinical trial information: NCT07058012 .