carfilzomib

Interestingly, carfilzomib-resistant cells were at least as sensitive to ATX-101 as the wild-type cells, suggesting both low cross-resistance between ATX-101 and proteasome inhibitors and elevated proteasomal stress in carfilzomib-resistant cells. Our multi-omics approach revealed a vital role of PCNA in regulation of proteasomal and ER stress in MM.

P1, N=125, Recruiting, K36 Therapeutics, Inc. | N=60 --> 125 | Trial completion date: Oct 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=17, Active, not recruiting, Hackensack Meridian Health | Trial completion date: Nov 2024 --> Sep 2025 | Trial primary completion date: Nov 2024 --> Sep 2025

P=N/A, N=26, Completed, University of Turin, Italy | Recruiting --> Completed | N=100 --> 26 | Trial completion date: Sep 2022 --> Dec 2024

Intriguingly, in an innovative co-culture system, canagliflozin enhanced CFZ-induced apoptosis in MM cells while protecting endothelial cells. These findings underscore the dual role of canagliflozin in reducing CFZ-induced endothelial toxicity, while enhancing its cytotoxic effect in MM.

A high-throughput screening of 221 anti-cancer drugs identified five candidates-bortezomib, carfilzomib, doxorubicin, panobinostat, and romidepsin-that demonstrated low IC50 values, indicating potential efficacy in treating CS. These findings suggest that NCC-CS1-C1 is a valuable tool for both preclinical and basic research on high-grade conventional central CS.

In the current ADVANCE study (NCT04268498), patients are randomly assigned to receive 8 cycles of carfilzomib-lenalidomide-dexamethasone with or without daratumumab (i.e. Dara-KRd versus KRd). High-dose melphalan (HDM) followed by autologous stem cell transplant (ASCT) is only offered to patients who remain MRD positive after 8 cycles with all patients transitioning to maintenance lenalidomide...Using MRD testing after completed combination therapy, patients will only be offered HDM-ASCT if they remain MRD-positive after 8 cycles; otherwise, they collected stem cells will be stored (delayed transplant) and transition to maintenance therapy. The aim of this translational effort is to define the underlying biology of sustained MRD negativity in NDMM patients.

P1, N=15, Not yet recruiting, Roswell Park Cancer Institute | Initiation date: Nov 2024 --> Feb 2025

P2, N=28, Not yet recruiting, Roswell Park Cancer Institute | Initiation date: Nov 2024 --> Feb 2025

Important advances include the development of compounds with novel MOA, including apratoxin and coibamide A analogues, modulating cotranslational translocation at the level of Sec61 in the endoplasmic reticulum, largazole and santacruzamate A targeting class I histone deacetylases, and proteasome inhibitors based on carmaphycins, resembling the approved drug carfilzomib...The review covers the state of current knowledge of marine cyanobacteria as anticancer agents with a focus on the mechanism, target identification and potential for drug development. We highlight the importance of solving the supply problem through chemical synthesis as well as illuminating the biological activity and in-depth mechanistic studies to increase the value of cyanobacterial natural products to catalyze their development.

P1/2, N=316, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Jun 2027 --> Apr 2025 | Recruiting --> Active, not recruiting

P1, N=100, Recruiting, University of Chicago | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P1/2, N=101, Active, not recruiting, University of Chicago | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=54, Completed, Amgen | Active, not recruiting --> Completed

DSF alone overcomes CFZ resistance through lipid peroxidation elevation and acts synergistically with CFZ in CFZ-resistant MM cell lines. Our results suggest that DSF is a promising anti-myeloma agent for overcoming CFZ resistance in MM through ferroptosisinduction.

P=N/A, N=50, Recruiting, The First Affiliated Hospital of Soochow University

We report results from the part 1, dose-finding component of the COMMANDER trial, testing the ability of Iber + daratumumab (dara) + dexamethasone (Iber-Dd) and Iber-Dd + carfilzomib (Iber-DKd) to upgrade response in MRD positive patients (pts) after AHCT. Conclusions Iber-Dd and Iber-DKd are safe combinations, able to significantly and rapidly reduce disease burden and lead to MRD negativity after modern induction therapy and AHCT in NDMM. This study is ongoing, complete safety and efficacy results from part 1 and updated results from part 2 will be presented.

P3, N=650, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Oct 2025 --> Feb 2026

Although the efficacy of carfilzomib was difficult to confirm due to its toxicity in our models, ibrutinib showed comparable efficacy to a standard combination of chemotherapy drugs. Together, our data provide a new culture method for IVLBCL PDX cells and a rationale for translating ibrutinib to clinical use in IVLBCL patients.

P1/2, N=70, Active, not recruiting, Wake Forest University Health Sciences | Trial completion date: Oct 2024 --> Nov 2032 | Trial primary completion date: Oct 2024 --> Apr 2029

P1/2, N=37, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

P1/2, N=63, Completed, European Myeloma Network B.V. | Active, not recruiting --> Completed

P2, N=50, Active, not recruiting, University of Arkansas | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P=N/A, N=586, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | N=1200 --> 586

P2, N=28, Not yet recruiting, Roswell Park Cancer Institute

P1, N=15, Not yet recruiting, Roswell Park Cancer Institute

Iber-Dd and Iber-DKd are safe combinations and able to eliminate MRD persistent after modern induction therapy and ASCT in NDMM. This study is ongoing, complete safety and efficacy results from part 1 and updated results from part 2 will be presented at the meeting.

P3, N=440, Not yet recruiting, Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

P=N/A, N=160, Recruiting, Takeda | N=320 --> 160 | Trial completion date: Oct 2025 --> Jun 2027 | Trial primary completion date: Oct 2025 --> Jun 2027

P2, N=74, Active, not recruiting, Weill Medical College of Cornell University | Trial completion date: Mar 2025 --> Mar 2026

P2, N=52, Active, not recruiting, Academic and Community Cancer Research United | Recruiting --> Active, not recruiting

P4, N=70, Recruiting, Beijing Chaoyang Hospital, Capital Medical University; Beijing Chaoyang Hospital, Capital Medical University

PIs enhance the anti-leukemic efficacy of CAR-expressing allogeneic NK cells against AML in vitro and in vivo, warranting further exploration of this combinatorial treatment within early phase clinical trials.

P1/2, N=300, Recruiting, Karyopharm Therapeutics Inc | Active, not recruiting --> Recruiting

Patients were treated either with carfilzomib, lenalidomide, and dexamethasone plus autologous stem cell transplant (KRd-ASCT, NCT01816971) or with daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd, NCT03500445). In addition to the prognostic significance of MS(-) at any level, the depth of MS negativity is associated with longer PFS. LC-MS(-) and/or 10-6 MRD(-) patients experience long term disease control. The potential of LC-MS to enhance the prognostic potential of MRD at 10-6 for predicting longer disease control is currently under evaluation in a larger sample set.

No abstract available

P1, N=189, Terminated, Pfizer | Active, not recruiting --> Terminated; A business decision was made by Pfizer to terminate the study. Termination was not due to any safety concerns, requests from regulatory authorities, changes to the benefit/risk profile or any new concerns regarding the investigational product.

P=N/A, N=36, Completed, Central Hospital, Nancy, France

P3, N=450, Recruiting, Kite, A Gilead Company | Not yet recruiting --> Recruiting

P1/2, N=66, Recruiting, Hackensack Meridian Health | Suspended --> Recruiting

P1, N=10, Recruiting, Tel-Aviv Sourasky Medical Center | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: Apr 2024 --> Apr 2026

P3, N=318, Not yet recruiting, Assistance Publique - Hôpitaux de Paris