carfilzomib

P2, N=20, Recruiting, Shanghai Changzheng Hospital

Anti-glioma effects with the lowest drug concentrations were achieved for proteasome inhibitors (carfilzomib, bortezomib, ixazomib), and HDAC inhibitors (panobinostat, romidepsin). The impact of their drug targets PSMB5 and HDAC1/2 on the growth of GBM cells was successfully validated by RNAi experiments. We established an aHTS platform for GBM TOs, and identified proteasome and HDAC inhibitors as promising drugs for the treatment of GBMs.

Mezigdomide-carfilzomib-dexamethasone provided a significant PFS benefit compared with carfilzomib-dexamethasone alone, with higher rates of grade 3 or 4 adverse events, including infections, which were mostly manageable with standard clinical practice and supportive care. These findings support mezigdomide-carfilzomib-dexamethasone as a clinically meaningful treatment option as early as first relapse in predominantly triple-class-exposed, anti-CD38 antibody-refractory and lenalidomide-refractory patients, a growing population with substantial unmet need.

Moreover, insulin and IGF-II attenuated apoptosis and the inhibition of cell migration induced by the proteasome inhibitors (PIs) bortezomib and carfilzomib, and these effects were reversed by IFITM1 knockdown. The ability of insulin to reduce bortezomib-induced apoptosis and G2/M phase cell cycle arrest was likewise dependent on IFITM1 expression. Collectively, these findings suggest that insulin-induced IFITM1 plays a pivotal role in MM progression and resistance to bortezomib, highlighting IFITM1 as a potential prognostic biomarker and therapeutic target.

P1/2, N=140, Recruiting, Australasian Myeloma Research Consortium | Active, not recruiting --> Recruiting | N=68 --> 140

This indicates that although proteasomal inhibition is not inflammatory, TNF present in the microvascular environment synergizes with the drugs to compromise endothelial function. Our observations provide an explanation for how microvascular damage potentially underlies tissue injury driven by Bortezomib or Carfilzomib.

P1, N=165, Recruiting, K36 Therapeutics, Inc. | N=125 --> 165

P3, N=500, Recruiting, Janssen Research & Development, LLC | Trial completion date: Jan 2029 --> Dec 2029

P2, N=50, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Mar 2026 --> Dec 2026

P2/3, N=153, Not yet recruiting, AstraZeneca AB | N=38 --> 153

P1/2, N=80, Active, not recruiting, University of Alabama at Birmingham | Trial completion date: Oct 2026 --> Aug 2028 | Trial primary completion date: Apr 2026 --> Aug 2028

P=N/A, N=100, Completed, Fondazione IRCCS Policlinico San Matteo di Pavia