P2, N=0, Withdrawn, Wake Forest University Health Sciences | N=17 --> 0 | Not yet recruiting --> Withdrawn

P2, N=0, Withdrawn, Cornerstone Pharmaceuticals | Not yet recruiting --> Withdrawn | N=20 --> 0

P1, N=24, Recruiting, Medical College of Wisconsin | Trial primary completion date: Aug 2026 --> Aug 2025

P2, N=20, Not yet recruiting, Cornerstone Pharmaceuticals

P2, N=6, Terminated, Wake Forest University Health Sciences | N=12 --> 6 | Trial completion date: Jun 2025 --> Jul 2024 | Recruiting --> Terminated; Low accruals

P1/2, N=75, Completed, University of Michigan Rogel Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Apr 2024

P2, N=24, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=75, Active, not recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Nov 2025 --> May 2025 | Trial primary completion date: Nov 2024 --> Apr 2024

P2, N=12, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: May 2024 --> Nov 2024

P2, N=17, Not yet recruiting, Wake Forest University Health Sciences | Trial primary completion date: Dec 2024 --> Apr 2025

P1, N=49, Completed, Wake Forest University Health Sciences | Phase classification: P2 --> P1

In patient-derived xenograft models of GBM in mice, the combination treatment of ABT263 and CPI-613 suppressed tumor growth and extended animal survival more potently than each compound on its own. Therefore, combined inhibition of Bcl-xL along with interference of the TCA-cycle might be a treatment strategy for GBM.

siRNA-mediated downregulation of ERp57/PDIA3 did not significantly induce ICT-mediated apoptosis in melanoma cells in the presence of CPI-613 and hydroxychloroquine. Therefore, the ICT antibody acts as a tumor suppressor in melanoma cells by targeting the cell membrane ERp57/PDIA3, expression of which was enhanced by the combination of CPI-613 and hydroxychloroquine.

P1/2, N=75, Active, not recruiting, University of Michigan Rogel Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Nov 2025 | Trial primary completion date: Jun 2024 --> Nov 2024

P2, N=12, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Dec 2023 --> May 2024

P1, N=16, Completed, Wake Forest University Health Sciences | Active, not recruiting --> Completed

P2, N=17, Not yet recruiting, Wake Forest University Health Sciences | Initiation date: Nov 2023 --> Feb 2024

These effects were related to modulation of multiple cell signaling pathways, including AMPK, RAS/ERK, and AKT/mTOR. Our findings demonstrate that simultaneous inhibition of multiple glycolytic enzymes (PDK1 and LDHA) is a promising novel therapeutic approach for LUAD.

Moreover, Benz and 64 together significantly suppressed the tumor growth in HCC827 cell mouse xenograft model. Taken together, our study may suggest that combined inhibition of HK2 and PDK1 using Benz and 64 could be a viable anticancer strategy for NSCLC.

P2, N=24, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

Taken together, our results demonstrated the role of TCA cycle in immune checkpoint blockade and provided a novel combination strategy for anti-PD-1 immunotherapy in melanoma treatment.

The first study to evaluate the survival between metastatic patients treated with CPI-613 versus borderline-resectable cases undergoing curative resection. Analysis revealed no significant differences in survival outcomes between the cohorts. Study results are suggestive that there may be potential utility with the addition of CPI-613 to potentially resectable pancreatic adenocarcinoma, although additional research with more comparable study groups are required.

P2, N=34, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=19, Completed, Wake Forest University Health Sciences | Active, not recruiting --> Completed | Trial completion date: Jun 2023 --> Jan 2023

P1/2, N=49, Active, not recruiting, David Bajor | Trial completion date: Apr 2024 --> Oct 2024 | Trial primary completion date: Apr 2023 --> Oct 2023

Devimistat in combination with GC is well tolerated and has an acceptable safety profile in patients with untreated advanced BTC.

P1/2, N=60, Not yet recruiting, University of Michigan Rogel Cancer Center

P1, N=21, Completed, Wake Forest University Health Sciences | Active, not recruiting --> Completed

P1/2, N=16, Completed, Cornerstone Pharmaceuticals | Recruiting --> Completed | N=59 --> 16 | Trial completion date: Nov 2024 --> Mar 2023 | Trial primary completion date: Aug 2023 --> Mar 2023

P2, N=17, Not yet recruiting, Wake Forest University Health Sciences

P1, N=19, Active, not recruiting, Wake Forest University Health Sciences | Trial completion date: Feb 2023 --> Jun 2023

In this work, we conjugated CPI-alkyne modified by Devimistat (CPI-613) with ruthenium-arene azide precursor Ru-N by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to construct Ru complex CPI-Ru...Moreover, CPI-Ru could significantly downregulate the expression of CD47 on the surface of K562 accompanied by the enhanced immune response by targeting the blockade of CD47. This work provides a new strategy for utilizing metal-based anticancer agents to block CD47 signal to achieve chemoimmunotherapy in chronic myeloid leukemia treatment.

As a result, DLST targeting of aberrant glutamine metabolism will have the dual benefit of reducing CD11b+Gr1+ cell-mediated immunosuppression while also directly inhibiting tumor growth. Thus CPI-613 represents an attractive drug to target glutamine addiction and reduce immunosuppressive environment plaguing ovarian cancer.

AG‑induced cell death was partially suppressed via PDK1 overexpression in lung cancer cells. Therefore, the anticancer effects of AG on human lung cancer cells may negatively regulate the expression of PDK1.

Both devimistat-treated and PDHA knockout cells displayed increased sensitivity to 2-deoxyglucose, demonstrating reliance on residual glycolysis. Taken together, this suggests that AML cells compensate for PDH and glycolysis inhibition by gluconeogenesis for maintenance of essential glycolytic intermediates and fatty acid oxidation, ACLY and ACSS2 for non-glycolytic production of acetyl-CoA. Strategies to target these escape pathways should be explored in AML.

P3, N=200, Terminated, Cornerstone Pharmaceuticals | Trial completion date: Aug 2021 --> Jan 2022

The results demonstrated that the PDK1- and PDK2-mediated Warburg effect contributes to the TGFβ1-enhanced stemness properties of HNC. Therefore, PDK1 and PDK2 may serve as molecular targets for the combination therapy of HNC.

P2, N=34, Recruiting, Memorial Sloan Kettering Cancer Center | N=26 --> 34

Our proteomic and structural investigations on resistant sublines indicate that DLD may represent a novel and potent target for overcoming vemurafenib resistance in melanoma cells.

P1, N=24, Recruiting, Medical College of Wisconsin | Not yet recruiting --> Recruiting

Discussion In conclusion, by leveraging the largest single-cell RNA-sequencing cohort of bone marrow samples from patients with MGUS and SMM, we uncovered novel insights into plasma cell malignancy, as well as differences in gene expression dysregulation between disease stages. Observations gleaned from this dataset could be used to nominate novel targets and prioritize target validation for the development of novel therapeutics for the treatment or prevention of MM.