BMS-986288

Furthermore, compared to the currently used Probody therapeutics for anti-CTLA-4 (BMS986288), ProCTLA-4 has more advantages in efficacy amplification, such as in poor immunogenic melanoma. Our design establishes an alternative paradigm for antibody agents that limits the emergence of immune-related adverse events (irAE) while increasing therapeutic efficacy.

P1/2, N=219, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | N=494 --> 219 | Trial completion date: May 2025 --> Aug 2024

P1/2, N=494, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Jun 2024 --> Oct 2024

P1/2, N=494, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

Background: Blockade of the CTLA-4 pathway with ipilimumab (IPI) as monotherapy or in combination with nivolumab (anti–PD-1) is an effective treatment for a variety of cancers...Here, we describe the preclinical characterization of 2 novel anti–CTLA-4 PB mAbs: anti–CTLA-4 PB (BMS-986249) is a peptide-masked version of IPI, and anti‒CTLA-4 nonfucosylated (NF) PB (BMS-986288) is a peptide-masked version of anti–CTLA-4 NF, which has enhanced antibody-dependent cellular cytotoxicity (ADCC) and regulatory T-cell (Treg) depletion compared with IPI. Antibody binding to CD16 was studied by surface plasmon resonance... These data demonstrate the potential of the PB-Tx technology platform to improve the therapeutic indices of anti–CTLA-4 PB and anti–CTLA-4 NF PB relative to their parental mAbs. The safety and antitumor activity of anti–CTLA-4 PB (NCT03369223) and anti–CTLA-4 NF PB (NCT03994601) are being investigated in patients with advanced solid cancers in ongoing phase 1 studies.