durcabtagene autoleucel (PHE885)

In 2021, idecabtagene vicleucel, a BCMA-targeting agent, became the first CAR-T therapy approved for relapsed/refractory MM, marking a significant milestone in MM treatment. Subsequently, ciltacabtagene autoleucel has also been approved...To address these challenges, strategies such as BCMA non-targeted or dual-targeted CAR-T, memory T cells, humanized CAR-T, and rapidly manufactured PHE885 cells have been developed...In conclusion, studies are exploring the use of CAR-T at an earlier stage, including at diagnosis, with an aim to replace ASCT. CAR-T has introduced a new dimension to MM treatment; however, limited efficacy in high-risk MM and the emergence of resistance to CAR-T remain key challenges to be addressed.

P2, N=147, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; The study was terminated since the sponsor made the decision to discontinue further development of the study drug durcabtagene autoleucel (PHE885).

P2, N=147, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P1, N=96, Terminated, Novartis Pharmaceuticals | Trial completion date: Feb 2026 --> Apr 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2026 --> Apr 2025; Business decision

P2, N=147, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2025 --> Jun 2025 | Trial primary completion date: Feb 2025 --> Jun 2025

P2, N=146, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2025 --> Feb 2025 | Trial primary completion date: Dec 2025 --> Feb 2025

P2, N=136, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting

P2, N=136, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P1, N=96, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

Our findings demonstrate that the T-Charge™ manufacturing platform successfully maintains highly heterogeneous transduced Tscm clones with self-renewal potential in durcabtagene autoleucel products. Maintenance of Tscm in manufactured products contributes to robust CAR-T expansion and long-term persistence of CAR-T cells with a highly diverse TCR repertoire after infusion.

In addition to its unique phenotype, PHE885 secretes up to 25 fold more target specific IL-2 and ~7 fold more IFN gamma in vitro , when comparing to the TM products either using the same lentiviral vector (TM_PHE885) or a clinically validated anti-BCMA vector (MCM998) . Based on these results, a Phase 1, open-label trial assessing PHE885 in patients with r/r MM (NCT04318327) was initiated. Initial data from the dose escalation portion of the Phase 1 study will be presented separately.