BMS-986449 / BMS - LARVOL DELTA

A Study of BMS-986449 With and Without Nivolumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=100 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2027 ➔ Sep 2026 | Trial primary completion date: May 2025 ➔ Sep 2026

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

The discovery of BMS-986449, a highly potent and selective degrader of the transcription factors Helios (IKZF2) and Eos (IKZF4) for the treatment of solid tumors (AACR 2025) - "Regulatory T (Treg) cell abundance in the tumor microenvironment is associated with poor responses to immunotherapies, such as nivolumab. In cynomolgus monkeys, oral administration of BMS-986449 (0.3 mg/kg, QD) was well-tolerated and maintained ≥80% degradation of Helios in circulating Treg cells over 24h. Given the positive outcomes from these pre-clinical studies and an acceptable safety profile, BMS-986449 was advanced into Phase I/II clinical trials for patients with advanced solid tumors."

Oncology • Solid Tumor • CRBN • IKZF1 • IKZF2

Selective degradation of Helios induces Treg cell reprogramming and enhanced antitumor immunity (AACR 2025) - "In tumor bearing hCRBN-KI mice, BMS-986449 daily dosing induced monotherapy activity in the CT26, MB49, and MC38 tumor models with TGI values of up to 75%, 62%, and 42%, respectively; in combination with anti-PD-1 immune checkpoint blockade more robust efficacy was achieved with TGI values of 95%, 97%, and 92%, respectively. Additionally, in cynomolgus monkeys, daily dosing of BMS-986449 (0.1 mg/kg) maintained greater than 80% degradation of Helios in circulating Treg cells, supporting the advancement of BMS-986449 into Phase 1/2 clinical trials for patients with advanced solid tumors."

IO biomarker • Oncology • Solid Tumor • CRBN • FOXP3 • GZMB • IKZF2