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). 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.

P2, N=80, Active, not recruiting, Dan Zandberg | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: Jul 2026 --> Oct 2027

P2, N=468, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed

P1, N=60, Not yet recruiting, Memorial Sloan Kettering Cancer Center

P2, N=12, Not yet recruiting, Nationwide Children's Hospital

To address this limitation, we developed tobemstomig, a novel bispecific antibody to preferentially and simultaneously block PD-1 and LAG-3 in cis on tumor-specific CD8 TILs, while sparing Tregs. It provided superior tumor growth inhibition in mouse models by replenishing stem-like cells and cytotoxic effector CD8 TILs, resulting in durable responses compared to monospecific antibodies targeting PD-1 and LAG-3 separately, which eroded the stem-like T cell pool over time.

P2, N=70, Suspended, Thomas Jefferson University | Recruiting --> Suspended

A personalized surgical approach to neoadjuvant ICI was feasible, with comparable recurrence rates between the patients who underwent INE and those who underwent TLND. For the patients without MPR, subsequent adjuvant therapy improved recurrence-free survival (p = 0.046). The ctDNA results correlated with the clinical outcomes, suggesting that ctDNA may complement pathologic response in guiding management.

P2, N=79, Recruiting, NSABP Foundation Inc | Trial primary completion date: Jun 2028 --> Apr 2029 | Not yet recruiting --> Recruiting

P2, N=44, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2028 --> May 2030 | Trial primary completion date: May 2028 --> May 2030

P1/2, N=120, Not yet recruiting, Regeneron Pharmaceuticals

Immune checkpoint receptors (LAG3, CD27) connect via PPI intermediates to Ca2+ and K+ channels, targetable by relatlimab (FDA-approved) and varlilumab (Phase 2). This work maps previously unknown links between CRC driver genes and ion channel regulation, with the ataluren-RPS21-KCNQ2 axis ready for pharmacological testing.