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DRUG:

Pixuvri (pixantrone)

i
Other names: BBR 2278, BBR-2278, BBR 2778, BBR-2778
Company:
Servier
Drug class:
Topoisomerase II inhibitor
Related drugs:
5ms
Pixantrone as a novel MCM2 inhibitor for ovarian cancer treatment. (PubMed, Eur J Pharmacol)
These findings suggest that pixantrone may be a promising drug for ovarian cancer patients by targeting MCM2 in the clinic.
Journal
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MCM2 (Minichromosome maintenance complex component 2)
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Pixuvri (pixantrone)
8ms
Oncogenic functions and therapeutic potentials of targeted inhibition of SMARCAL1 in small cell lung cancer. (PubMed, Cancer Lett)
Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.
Journal
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SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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Pixuvri (pixantrone)
1year
Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for hepatocellular carcinoma. (PubMed, Hepatology)
HOIL-1 is critical in promoting sorafenib resistance and CSC properties of HCC through Notch1 signaling. Pixantrone targeting HOIL-1 restrains the sorafenib resistance and provides a potential therapeutic intervention for HCC.
Journal
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NOTCH1 (Notch 1)
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sorafenib • Pixuvri (pixantrone)
1year
PIVeR: Study of Pixantrone in CD20+ Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma (clinicaltrials.gov)
P2, N=74, Active, not recruiting, The Lymphoma Academic Research Organisation | Recruiting --> Active, not recruiting
Enrollment closed
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CD20 (Membrane Spanning 4-Domains A1)
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Rituxan (rituximab) • ifosfamide • etoposide IV • Pixuvri (pixantrone)
over1year
Long-term efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma achieving a complete response with pixantrone. (PubMed, Eur J Haematol)
In this real-life experience, pixantrone demonstrated long-term efficacy in a cohort of R/R DLBCL cases who had previously received at least two prior regimens; many of whom had characteristics associated with poor prognosis.
Observational data • Retrospective data • Journal
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Pixuvri (pixantrone)
over1year
Journal
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Rituxan (rituximab) • lenalidomide • doxorubicin hydrochloride • cyclophosphamide • Xpovio (selinexor) • vincristine • prednisone • Epkinly (epcoritamab-bysp) • Pixuvri (pixantrone) • Monjuvi (tafasitamab-cxix) • Lunsumio (mosunetuzumab-axgb)
over1year
LONG-TERM FOLLOW-UP AND GENE EXPRESSION PROFILES ASSOCIATED WITH OUTCOME IN PATIENTS WITH RELAPSED AGGRESSIVE B- OR T-CELL LYMPHOMAS TREATED IN THE NORDIC P[R]EBEN TRIAL (ICML 2023)
"The research was funded by: Servier Laboratoires Introduction: The Nordic Lymphoma Group (NLG) performed a dose-finding/expansion trial evaluating pixantrone, etoposide, bendamustine and, in CD20+ lymphomas, rituximab (P[R]EBEN) in patients (pts) with relapsed diffuse large B-cell (DLBCL) or peripheral T-cell (PTCL) lymphomas. The P[R]EBEN regimen is feasible on an out-pt basis and shows encouraging response rates and DoR. In PTCL, we observed an overrepresentation of AML/MDS, possibly related to the use of etoposide in multiple treatment lines. Gene expression analysis identified signatures and single genes predictive of long-term response."
Clinical
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CD20 (Membrane Spanning 4-Domains A1) • NCF4 (Neutrophil Cytosolic Factor 4) • NCOA3 (Nuclear Receptor Coactivator 3)
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nCounter® PanCancer Immune Profiling Panel • nCounter® PanCancer Pathways Panel
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Rituxan (rituximab) • etoposide IV • bendamustine • Pixuvri (pixantrone)
over2years
Randomized Phase II Study of Two Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance). (PubMed, Oncologist)
Pixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: NCT01086605).
P2 data • Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 negative
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mitoxantrone • Pixuvri (pixantrone)
almost3years
In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives. (PubMed, Cells)
Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. Compound 4 enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.
Preclinical • Journal
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PARP1 (Poly(ADP-Ribose) Polymerase 1) • CASP3 (Caspase 3) • MAP1LC3A (Microtubule Associated Protein 1 Light Chain 3 Alpha)
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mitoxantrone • Pixuvri (pixantrone)
over3years
[VIRTUAL] FINAL ANALYSIS OF A NORDIC LYMPHOMA GROUP PHASE IB/IIA TRIAL OF PIXANTRONE, ETOPOSIDE, BENDAMUSTINE AND, IN CD20-POSITIVE TUMORS, RITUXIMAB IN RELAPSED AGGRESSIVE B- OR T-CELL LYMPHOMAS (ICML 2021)
The P[R]EBEN regimen is a feasible out-patient based treatment, applicable in frail, heavily pre-treated aggressive lymphoma pts and shows encouraging CR rates and DoR, particularly in early responders.
P1/2 data
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CD20 (Membrane Spanning 4-Domains A1)
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CD20 positive
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Rituxan (rituximab) • etoposide IV • bendamustine • Pixuvri (pixantrone)
over3years
[VIRTUAL] CLINICAL OUTCOMES IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA RECEIVING CONVENTIONAL THIRD-LINE THERAPY: A MULTICENTER, RETROSPECTIVE, REAL-WORLD STUDY IN THE UNITED KINGDOM (EHA 2021)
All patients had received rituximab, 11% received prior auto-HSCT (n=14), and 57% were chemotherapy refractory (n=73). The most common 3L treatment regimens were salvage chemotherapy without an anti-CD20 mAb (44%, n=57), salvage chemotherapy with an anti-CD20 mAb (22%, n=28), salvage chemotherapy followed by auto-HSCT (10%, n=13) or allogeneic HSCT (8%, n=10), pixantrone (4%, n=5), and lenalidomide (4%, n=5), respectively...Additional analyses for patient subgroups will be presented. Conclusion This UK real-world analysis provides insights into clinical practice and highlights the poor outcomes achieved with conventional (non–CAR T cell) 3L treatment options in the UK, demonstrating the need for more effective treatments in patients with R/R LBCLs.
Clinical data • Retrospective data • Real-world evidence
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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BCL6 rearrangement • BCL2 rearrangement
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Rituxan (rituximab) • lenalidomide • Pixuvri (pixantrone)
4years
Clinical • Enrollment change • Trial withdrawal
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CD20 (Membrane Spanning 4-Domains A1)
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Rituxan (rituximab) • fludarabine IV • Pixuvri (pixantrone)
4years
Effectiveness and Safety of Pixantrone for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Every-Day Clinical Practice: The Italian Cohort of the PIXA Registry. (PubMed, Acta Haematol)
Our data documented drug efficacy that is satisfactory for this high-risk subset of patients with an acceptable toxicity profile. Results indicate that pixantrone could be a significant treatment option in patients with R/R aggressive DLBCL treated in everyday clinical practice.
Clinical • Journal
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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BCL2 positive
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Pixuvri (pixantrone)
4years
Enrollment change • Trial withdrawal
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CD20 (Membrane Spanning 4-Domains A1)
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Rituxan (rituximab) • fludarabine IV • Pixuvri (pixantrone)