Phase 2 cemiplimab PD-1 antibody trial adds fianlimab LAG-3 and REGN7075 EGFR×CD28 bispecific.

NSABP Foundation’s EMPIRE (NSABP FC-13) is an open-label, randomized Phase 2 platform study testing whether adjuvant immunotherapy can clear ctDNA-defined minimal residual disease (MRD) and reduce recurrence after definitive therapy for colorectal cancer. Eligible patients have microsatellite-stable (MSS) stage II–III colon/rectal cancer or oligometastatic stage IV CRC and are ctDNA-positive (Signatera) after surgery and standard chemotherapy/chemoradiotherapy, but without radiographic recurrence. Arms compare Regeneron/Sanofi’s cemiplimab (Libtayo; anti–PD-1) alone vs cemiplimab + fianlimab (anti–LAG-3) vs cemiplimab + REGN7075 (EGFR×CD28 costimulatory bispecific designed to enhance T-cell activation in the tumor microenvironment) given on a q3-week schedule for about a year. The key scientific/commercial angle is bringing “MRD interception” into largely IO-resistant MSS CRC, using ctDNA to enrich for patients at highest relapse risk and then intensifying immune activation beyond PD-1 alone. Today’s care after curative-intent surgery is observation/surveillance after completing adjuvant chemo (and pelvic chemoradiation for many rectal cases), with treatment typically restarting only at overt recurrence—this study tests whether acting earlier at ctDNA positivity can change that trajectory.