P2, N=29, Completed, Virginia G. Kaklamani | Unknown status --> Completed

These data support further clinical development for the combination of copanlisib and eribulin. These data led to a phase I/II trial of copanlisib and eribulin in patients with metastatic TNBC.

P1, N=50, Recruiting, TOLREMO therapeutics AG

P2, N=74, Recruiting, Fudan University

Here, we discover that targeting EP300/CBP using the domain-specific inhibitors, A485 (HAT) or CCS1477 (BRD) have different effects in select tumor types...Mechanistically, bromodomain inhibition causes rapid disruption of genetic dependency networks that are required for G3MB growth. These studies provide a domain-specific structural foundation for drug discovery efforts targeting EP300/CBP and identify a selective role for the EP300/CBP bromodomain in maintaining genetic dependency networks in G3MB.

Herein, we report the design, synthesis, and biological evaluation of a series of cereblon (CRBN)-recruiting CBP/p300 proteolysis targeting chimeras (PROTACs) based on the inhibitor CCS1477...14g and 14h displayed remarkable antitumor efficacy in the MV4;11 xenograft model (TGI = 88% and 93%, respectively). Our findings demonstrated that 14g and 14h are useful lead compounds and deserve further optimization and activity evaluation for the treatment of human cancers.

These findings provide an epigenetic mechanism of action of eribulin, supporting its use early in the disease process for MET induction to prevent metastatic progression and chemoresistance. These findings warrant prospective clinical evaluation of the chemosensitizing effects of eribulin in the treatment-naive setting.

P2, N=10, Not yet recruiting, Fudan University

P2; Changes in ctDNA can occur rapidly and reflect changes in patients' clinical tumour responses (NCT02681523).

A combined inhibitor of these three proteins, NEO2734, reduced the growth of both AR-positive and AR-null organoids, as measured by changes in viability, size, and composition..

We found that eribulin-induced cell death was reduced by ferroptosis inhibitors; deferoxamine, an iron chelator and ferrostatin-1, a lipid peroxidation inhibitor...The combination of eribulin and ML210, a glutathione peroxidase 4-inhibiting ferroptosis inducer, had a synergistic effect on ferroptosis. Taken together, our findings show firstly that eribulin triggers ferroptosis in OCCC and this effect occurs via the suppression of the Nrf2-HO-1 signaling pathway, SOD activity and the promotion of lipid peroxidation. These findings suggest that eribulin-induced ferroptosis is associated with its anti-tumor effect and also could be a potential therapeutic target in OCCC.

P1, N=181, Recruiting, Eisai Inc. | Trial completion date: Oct 2024 --> Mar 2027 | Trial primary completion date: Oct 2024 --> Mar 2027

P1, N=8, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

P1, N=15, Active, not recruiting, OHSU Knight Cancer Institute | Phase classification: P1b --> P1

P2, N=81, Not yet recruiting, Zhejiang Cancer Hospital

P2, N=30, Recruiting, Criterium, Inc. | Trial completion date: May 2025 --> Aug 2027 | Trial primary completion date: Nov 2023 --> Jun 2027

We also observed differential gene expression and induced immune cell infiltration in tumors pretreated with ICG-001 and then treated with CAR T cells as compared with single treatment groups or when ICG-001 treatment was administered after CAR T cell therapy. We conclude that specific Wnt/CBP/β-catenin antagonism results in pleotropic changes in the glioma TME, including glioma stem cell differentiation, modulation of the stroma, and immune cell activation and recruitment, thereby suggesting a possible role for enhancing immunotherapy in glioma patients.

P1, N=70, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting

P3, N=302, Recruiting, Sun Yat-sen University

P3, N=170, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P2; Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1/2, N=132, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Aug 2024 | Trial primary completion date: Dec 2023 --> Aug 2024

P3, N=170, Suspended, National Cancer Institute (NCI) | N=465 --> 170

Materials & MDA-MB 231 cells were treated with eribulin and paclitaxel, and the samples from 53 patients treated with neoadjuvant eribulin were compared with those from 14 patients who received the standard-of-care treatment using immunohistochemistry. Eribulin treatment caused significant DNA methylation changes in drug-tolerant persister TNBC cells, and it also elicited changes in the expression levels of epigenetic modifiers (DNMT1, TET1, DNMT3A/B) in vitro and in primary TNBC tumors. These findings provide new insights into eribulin's mechanism of action and potential biomarkers for predicting TNBC treatment response.

Consistent with this notion, β-catenin inhibition using XAV939 or ICG-001 partially prevented centrinone-induced death and rescued the growth two APC-mutant organoid lines tested. Our study reveals a novel role for canonical WNT signaling in regulating centrosome loss-induced growth defect/death in a subset of APC-mutant colorectal cancer independently of the classical p53 pathway.

Postoperative adjuvant fluorouracil plus epirubicin HCl plus cyclophosphamide(FEC)plus paclitaxel(PTX)therapy was administered...Capecitabine was selected for treatment of the recurrent lesion...At this time, eribulin mesylate was selected, along with intensity-modulated radiation therapy(IMRT)...Subsequently, liver metastasis was detected, and the drug was switched to vinorelbine ditartrate(a drug with less non-hematological toxicity)...About half a year later, ie, in October 2021(11 years after the surgery), we detected an increase in the size of the liver metastasis and selected atezolizumab and nab-PTX for treatment. Applicable regimens of drug therapy are still available at present and drug therapy has been continued based on a discussion and mutual understanding of the adverse reactions, etc. with the patient. Few reports have been published concerning long-term survivors among TN breast cancer cases.

Based upon the clinical p300/CBP bromodomain inhibitor CCS1477, a conformational restriction strategy was used to optimize the linker to generate a series of PROTACs, culminating in the identification of QC-182...Notably, QC-182 potently depletes p300/CBP proteins in mouse SK-HEP-1 xenograft tumor tissue. QC-182 is a promising lead compound toward the development of p300/CBP-targeted HCC therapy.

Our real-world study suggests that eribulin may be a potential treatment option for MBC patients who fail a prior PI3K inhibitor.

Promising antitumor activity was observed with E7389-LF in combination with nivolumab in patients with GC, and no new safety signals were observed, compared with either monotherapy.

P1, N=50, Recruiting, Aurigene Discovery Technologies Limited | Not yet recruiting --> Recruiting

The combination of eribulin and pembrolizumab demonstrated promising activity in LPS and angiosarcoma.

Results show complex synergistic interactions between eribulin, fulvestrant, and palbociclib, and point to a particularly robust synergy when combining all three drugs.

P1/2, N=106, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=30, Recruiting, Australia New Zealand Gynaecological Oncology Group

P2, N=252, Recruiting, Guangdong Provincial People's Hospital | Not yet recruiting --> Recruiting

Other drugs, such as imatinib, figitumumab, axitinib, and eribulin, are also being tested. Definitive radiotherapy appears to be a promising therapeutic modality. Since standards for the treatment of advanced and metastatic diseases are not available, further investigation of novel agents is necessary.

Of the drugs used in second-line chemotherapy for soft tissue sarcoma (STS), trabectedin is effective for liposarcoma and leiomyosarcoma (L-sarcoma), eribulin for liposarcoma, and pazopanib for non-liposarcoma. The present study demonstrated the potential of tailored therapy guided by mutation profiles established by comprehensive genomic profiling testing in optimizing second-line chemotherapy for STS. The findings of this study will hopefully contribute some valuable insights into enhancing STS treatment strategies and outcomes.

P1, N=181, Recruiting, Eisai Inc. | Phase classification: P1b --> P1

In summary, acetyl-α-tubulin-lys40 was increased in HCC and was associated with a shorter overall survival of HCC patients. Reducing the level of acetyl-α-tubulin-lys40 can enhance sensitivity to Eribulin treatment both in vitro and in vivo, thereby establishing acetyl-α-tubulin-lys40 as a potential prognostic marker and predictive indicator for Eribulin treatment in HCC patients.

These exploratory tumor biomarker analyses suggest that E7386 in combination with lenvatinib may affect the tumor microenvironment in HCC pts through effects on Wnt signaling, angiogenesis, hypoxic response, and glycolysis pathways. This concept is the basis for treatment with this combination. However, given the small sample size, further investigation is needed to confirm these effects on the tumor microenvironment.

P2, N=30, Recruiting, Sanhuan Cancer Hospital, Chaoyang District, Beijing; Sanhuan Cancer Hospital

P1/2, N=156, Recruiting, Eisai Inc. | Phase classification: P1b/2 --> P1/2