Ninlaro (ixazomib)

The IRd regimen demonstrates enhanced clinical efficacy in RRMM management, maintaining a safety profile comparable to the conventional Rd regimen. Furthermore, it effectively improves bone metabolism, reduces serum inflammation, and modulates serum biochemical parameters. Elevated M-protein expression correlates with poorer treatment outcome in RRMM.

To mimic ChaC1 overexpression by inducing endogenous ChaC1 high expression, a complementary ChaC1-induction-based screening was performed and revealed proteasome inhibitors (e.g., bortezomib, ixazomib, delanzomib) as potent inducers of endogenous ChaC1 via ATF4-dependent transcriptional activation. This functional convergence demonstrates that ChaC1 activation, either achieved through genetic manipulation or pharmacological induction, creates a synthetic lethal context for AUR in HCC cells. Together, our study establishes a ChaC1-based pharmacological discovery platform that identifies proteasome inhibitor and auranofin combination as a mechanistically rational anti-HCC strategy, providing both methodological innovation in drug repurposing screening and immediate translational potential for HCC treatment.

P1, N=24, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

Rencofilstat increased extracellular secretion of cyclophilin B, but rencofilstat + ixazomib reduced glycosylation and, likely, the biological function of CD147 (CypB receptor) and decreased downstream ERK signaling. Rencofilstat + ixazomib may be a new strategy for increasing proteotoxic stress and apoptotic cell death in advanced prostate cancer cells with less toxic side effects.

P2, N=40, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027

Proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib are FDA-approved treatments for multiple myeloma, but resistance frequently limits their effectiveness...Importantly, aclarubicin, a non-DNA-damaging anthracycline, also attenuated Nrf1 transcriptional activity, indicating that DNA damage is not required for this inhibition. Doxorubicin co-treatment delayed proteasome recovery after pulse inhibition and partially restored sensitivity to carfilzomib in bortezomib-resistant U266 myeloma cells, consistent with genetic knockout of Nrf1. These findings identify a DNA-damage-independent mechanism by which anthracyclines directly obstruct Nrf1-mediated transcriptional induction. Thus, anthracyclines serve as chemical tools to probe the molecular control of proteostasis and suggest a strategy to mitigate Nrf1-driven adaptive response to proteasome inhibition.

P2, N=23, Terminated, University of California, San Diego | Completed --> Terminated; The trial met its primary endpoint.

P1, N=30, Terminated, University of Pennsylvania | Trial completion date: Jul 2026 --> Jul 2025 | Active, not recruiting --> Terminated; Slow accrual at the time when sufficient participants were already enrolled to answer the scientific question posed by the study.

P2, N=236, Active, not recruiting, Washington University School of Medicine | Trial completion date: Aug 2025 --> Aug 2026

To address this, we investigated the impact of the immune system on survival outcomes of 89 newly diagnosed MM patients in the HOVON-143 trial, where frail or intermediate-fit patients received daratumumab-ixazomib-dexamethasone. Using the most predictive immune parameters, we subsequently developed two immune risk scores-one for PFS and one for OS-which remained strongly associated with survival after adjusting for frailty status, disease stage, and cytogenetic risk. Our findings underscore the importance of a composite analysis of the immune system and demonstrate the association of baseline immune parameters with survival outcomes of first-line therapy in non-fit MM patients.

P2, N=23, Completed, University of California, San Diego | Active, not recruiting --> Completed | N=46 --> 23 | Trial completion date: Oct 2026 --> Jul 2025 | Trial primary completion date: Mar 2026 --> Jul 2025

P2, N=66, Completed, GWT-TUD GmbH | Active, not recruiting --> Completed