What question did this study set out to answer?

The trial aims to assess the effectiveness of cemiplimab monotherapy and combinations in colorectal cancer patients with ctDNA positivity post-therapy.

May 30, 2026

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.

Key Points

The trial aims to assess the effectiveness of cemiplimab monotherapy and combinations in colorectal cancer patients with ctDNA positivity post-therapy.
Multicenter Phase II randomized trial
Patients with MSS stage II–III or oligometastatic stage IV CRC who are ctDNA-positive
Three treatment arms: Cemiplimab alone or with fianlimab or REGN7075, each for 1 year.
Primary endpoint: ctDNA clearance at 12 weeks without radiographic recurrence is evaluated
Secondary endpoints include recurrence-free survival and safety monitoring
Statistical design allows up to 33 patients in Arm 1 and 23 each in Arms 2 and 3.

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 α=0.05, power=0.78). Status: Enrollment began in September 2025 across NSABP Foundation sites and is ongoing. Clinical trial information: NCT07058012 .

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