P1, N=10, Terminated, Bexion Pharmaceuticals, Inc. | Trial completion date: Dec 2025 --> Oct 2024 | Active, not recruiting --> Terminated; Bexion Pharmaceuticals has decided to close the BXQ-350.AD study to enrollment prior to the anticipated enrollment goal. Justification for this decision is due to slow enrollment and the competitive landscape of the indication.

P2, N=60, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1/2, N=195, Active, not recruiting, Bexion Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

P1, N=5, Terminated, Bexion Pharmaceuticals, Inc. | N=50 --> 5 | Enrolling by invitation --> Terminated; Bexion Pharmaceuticals no longer has open studies in which subjects would be eligible to rollover and continue treatment under the BXQ-350.AE protocol. Therefore, no additional subjects will be enrolled in this trial.

P=N/A, N=0, Available, Telix Pharmaceuticals (Innovations) Pty Limited

P1, N=21, Active, not recruiting, Bexion Pharmaceuticals, Inc. | Trial primary completion date: Sep 2024 --> Dec 2024

Our findings allow a novel interpretation of the interplay between NOX 2 activation and mitoO2.- formation induced by ATO, ultimately steering leukemic cells towards MPT-dependent apoptosis. These mechanistic insights provide a rationale for the disparate responses of APL and AML cells to ATO, offering potential avenues for the development of therapeutic intervention tailored to specific leukemia subtypes.

Diagnosis relies on clinical, morphological, phenotypic, and cytogenetic evidence, with treatment involving all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Hypogranular acute promyelocytic leukemia (AML3v) is a rare form and is even rarer when it is discovered following an ischaemic event, which is what makes our case so special.

KYNU can promote GC proliferation, invasion, metastasis, and cuproptosis resistance.This effect is not associated with its metabolite 3-HA, but is achieved by a non classical mechanisms that downregulating the expression of LIAS, a key gene of cuproptosis.

The additive effect of CTLA-4 knockdown together with Docetaxel treatment significantly downregulated BCL-2 level and upregulated BAX expression. Our findings support the idea that combining chemotherapy such as Docetaxel with efficient targeted therapy against inhibitory immune checkpoints can be a promising strategy in cancer treatment.

P3, N=180, Recruiting, Luye Pharma Group Ltd. | Not yet recruiting --> Recruiting

Interestingly, our study shows that lurbinectedin treatment upregulates MHC-I/II genes and CD8 in SCLC clinical samples. We provide mechanistic insights into the effect of lurbinectedin on STING-mediated multimodal immune activation and demonstrate that lurbinectedin treatment represents a promising therapeutic strategy to potentiate the efficacy of immunotherapy in SCLC.

Finally, p53 agonists and elesclomol coordinately suppress the growth of cancer in a xenograft mouse model. Altogether, our study uncovers that p53 promotes glycolytic reprogramming and cuproptosis via circFRMD4A and suggests a potential combination strategy against cancers with wild-type p53.

Notably, gene silencing experiments confirmed the critical roles of both NRF2 and AHR in mediating ATOIII-induced NQO1 expression. In conclusion, ATOIII exposure is found to upregulate the NQO1 enzyme through a transcriptional mechanism via AHR- and NRF2- dependent mechanisms, offering valuable insights into its therapeutic mechanisms.

This simple, cost-effective tool, with its easy-to-read format, is particularly valuable in under-resourced regions. The assay facilitates timely diagnosis and prompt administration of lifesaving therapies such as all-trans retinoic acid and arsenic trioxide in APL.

The classical cuproptosis inducer, ES-Cu (elesclomol plus copper), increases the protein stability of the transcription factor NFE2L2 (also known as NRF2), leading to the upregulation of gene expression of glutamate-cysteine ligase modifier subunit (GCLM) and glutamate-cysteine ligase catalytic subunit (GCLC)...Consequently, genetic inhibition of the NFE2L2-GSH-SLC25A39 pathway enhances cuproptosis-mediated tumor suppression in cell culture and in mouse tumor models. These findings not only reveal distinct mechanisms of GSH in inhibiting cuproptosis and ferroptosis, but also suggest a potential combination strategy to suppress PDAC tumor growth.

P1, N=9, Withdrawn, Flinders University | Recruiting --> Withdrawn

The present research depicted that BIS and TMZ have the potential to protect the heart and provide therapeutic benefits by preventing acute heart injury induced by ATO. This is achieved by reversing the redox-sensitive pathway, reducing inflammation, and inhibiting apoptosis.

This study demonstrates the therapeutic potential of venetoclax in combination with ATO in vitro and strongly encourages further investigation of relapsed/refractory APL with high BCL2 expression.

P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Trial completion date: Jun 2026 --> Jun 2027

P2, N=34, Active, not recruiting, TaiRx, Inc. | Trial completion date: Dec 2024 --> Dec 2025

Moreover, we observed a positive correlation between sample immune infiltration and sample resistance to elesclomol and panobinostat, whereas a negative correlation was found with venetoclax resistance. Our study enriches the current AML risk stratification and provides guidance for precision medicine in AML.

Our findings verify the therapeutic effects of targeting LIF in SFN-resistance, uncover the potential mechanism for the increased sensitivity to SFN and sought to elucidate how this intervention might contribute to overcoming SFN resistance. KLTI is a promising immunomodulatory drug by regulating LIF and macrophage-NK cell interaction, which could be a potential combination partner for HCC treatment.

P1, N=30, Recruiting, Taivex Therapeutics Corporation | Trial completion date: Dec 2025 --> Jul 2027 | Trial primary completion date: Jun 2024 --> Jun 2026

P1/2, N=62, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Jul 2025

Furthermore, combining ES@Cu(Ⅱ)-MOF with an anti-programmed cell death-ligand 1 (PD-L1) antibody converted the immunosuppressive tumor microenvironment to an immunogenic microenvironment, thus effectively inhibiting breast tumor growth. Overall, this work provides an innovative approach utilizing nanozymes to facilitate cuproptosis for cancer treatment, which potentially enhances the effectiveness of immune checkpoint inhibitor-based immunotherapy.

P1/2, N=0, Withdrawn, University of California, San Francisco | N=70 --> 0 | Not yet recruiting --> Withdrawn

Foretinib and elesclomol were predicted to exert strong inhibitory effects on SW13 cells by inhibiting the expression of CDH2 and CDH13. These data indicate that CDH2 and CDH13 are promising targets for precise treatment of ACC and may serve as new biomarkers for ACC prognosis.

Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.

P=N/A, N=15, Recruiting, The First Hospital of China Medical University; The First Hospital of China Medical University

Our research reveals that low-dose ATO, by regulating LOXL3, remodels the ECM and enhances CD8+T cell infiltration, thus sensitizing the efficacy of immunotherapy, which provides a novel strategy for comprehensive treatment to PC.

With Cu-DPPZ-Py+ and Cu-Elesclomol, there is strong evidence that the triggering cuproptosis significantly drives mitochondrial DNA (mtDNA) release to activate innate immunity via cyclic GMP-AMP synthase-stimulation of interferon genes (cGAS-STING), which can improve T cell antitumor immunity in vivo. By contrast, it is observed that Cu-DPPZ-Ph treated tumor cells could release intracellular caspase-3, resulting in apoptosis-associated immunosuppression. This study supports insights into how cuproptosis bridges cGAS-STING immune pathways, contributing to the development of cuproptosis-based antitumor immunotherapy.

This review discusses several potent alkaloids, such as homoharringtonine, chaetominine, matrine, and jerantinine B, which induce apoptosis, cell cycle arrest, and autophagy and inhibit signaling pathways including PI3K/Akt/mTOR, MAPK, and NF-κB...In addition, targeting leukemia stem cells (LSCs) with alkaloids such as zalypsis offers promise due to its ability to induce apoptosis without significantly affecting normal hematopoietic stem cells...For example, jerantinine B targets AML cells, while vincristine has shown success in lymphocytic leukemia...However, adverse effects such as neutropenia and hepatotoxicity necessitate careful management. Collectively, these findings emphasize the need for further research into alkaloid-based combination therapies to enhance efficacy and minimize toxicity, providing a promising avenue for innovative leukemia treatments.

Taken together, our results confirm that HHT is a substrate for MDR1. It opens the door to a new opportunity to clinically evaluate HHT and its derivatives for the treatment of AML and other cancers.

P1/2, N=158, Recruiting, Genprex, Inc. | Trial completion date: Dec 2027 --> Mar 2029 | Trial primary completion date: Dec 2026 --> Mar 2028

P1/2, N=49, Recruiting, Neonc Technologies, Inc. | Trial primary completion date: Jun 2024 --> Dec 2024

P1, N=15, Not yet recruiting, Neonc Technologies, Inc. | Trial completion date: Oct 2024 --> Oct 2025 | Initiation date: May 2024 --> Dec 2024 | Trial primary completion date: Oct 2024 --> Oct 2025

Our data provide additional insight into mitochondrial stress and ICD in response to PT-112. PT-112 anticancer immunogenicity could have clinical applications and is currently under investigation in a Phase 2 mCRPC study.

P=N/A, N=1000, Not yet recruiting, Karolinska Institutet

P1, N=30, Not yet recruiting, Virginia Commonwealth University

This multicenter phase 1 study sought to determine the MTD of oral Lisavanbulin in combination with standard RT (60 Gy/30 fractions) but without temozolomide in patients with newly diagnosed MGMT promoter unmethylated GBM (uGBM). Avanbulin exposures increased in a relatively dose-proportional manner with increasing oral dose of Lisavanbulin from 4 to 15 mg. Lisavanbulin in combination with RT was considered safe up to the highest predefined oral dose level of 15 mg daily.

In conclusion, the anti-inflammatory effect of ATO can effectively alleviate the ALV-J pathogenic process. ALV-J serves as a model virus for antiviral tumor research, while ATO provides references for the treatment of such tumors.