Pixuvri (pixantrone) / Servier - LARVOL DELTA

PICKING STRONG BRIDGING REGIMENS BEFORE CD19 CAR-T CELL THERAPY OF LARGE B CELL LYMPHOMA – HOW HISTOLOGY AND HIGH LDH IMPACT LONG-TERM OUTCOMES (EBMT 2026) - "Bridging choices were grouped as No-Bridging, radiotherapy, ancient (Pixantrone, CHOP-variants), intensive (e.g., R-DHAP, R-MATRIX), R-gemcitabine/oxaliplatin (R-GemOx), sequential, R-Polatuzumab (R-Pola), or R-Pola-Bendamustine (Pola-BR)... 508 patients (384 DLBCL-NOS, 124 trFL) treated with Axi-cel (65.2%), Tisa-cel (25.4%), or Liso-cel (9.4%) were included... Our dataset is limited by the retrospective nature including a possible bias that worse bridging outcome may prevent patients from CAR-T infusion. We found outcomes were distinct for trFL and DLBCL-NOS. In NOS, responses to bridging as well as any LDH-elevation strongly and independently influenced outcomes."

CAR T-Cell Therapy • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

Design and optimization of small-molecule PROTACs targeting KRAS (AACR 2026) - "Based on this, we synthesized a library of PROTACs with various lengths of alkyl linkers tethering Pixantrone, the warhead targeting KRAS, to Pomalidomide, a well-known E3 ligase recruiter. Moving forward, we are shifting our efforts toward validating other candidates from the screen, since PROTAC efficacy may be independent of kinase inhibition efficacy of the warhead alone. If successful, an improved PROTAC design may overcome the clinical ineffectiveness of the current generation of allosteric inhibitors."

Oncology • Pancreatic Cancer • Solid Tumor • KRAS

PIVeR: Study of Pixantrone in CD20+ Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=74 | Completed | Sponsor: The Lymphoma Academic Research Organisation | Active, not recruiting ➔ Completed

Trial completion • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

S00854: Serial cardiac magnetic resonance imaging (CMR) with contrast agents and biomarker analysis for the detection of cardiotoxicity nunder anthracycline-containing cancer therapy - A monocentric, low interventional Phase IV pilot study (clinicaltrialsregister.eu) - P4 | N=93 | Recruiting | Sponsor: Robert Bosch Gesellschaft fuer medizinische Forschung mbH | Not yet recruiting ➔ Recruiting

Biomarker • Enrollment open • Cardiovascular • Oncology

Real-world single-center experience with pixantrone in DLBCL prior to its withdrawal: clinical outcomes and exploratory immunologic observations. (PubMed, Ann Hematol) - No abstract available

Clinical data • Journal • Real-world evidence • Diffuse Large B Cell Lymphoma • Oncology

A charge-reversal prodrug activated by tumor-acidity for selective cancer chemotherapy. (PubMed, Biomater Sci) - "Herein, we developed a charge-reversal prodrug, PIX-DMMA, synthesized through the reaction between primary amino groups of pixantrone (PIX) and 2,3-dimethylmaleic anhydride (DMMA)...Furthermore, in vivo studies in LoVo tumor-bearing mice showed significant tumor growth inhibition without significant systemic toxicity. This acid-triggered charge-reversal prodrug represents a promising strategy for selective cancer therapy."

Journal • Oncology

Search for acetylcholinesterase inhibitors by computerized screening of approved drug compounds. (PubMed, SAR QSAR Environ Res) - "Notable candidates include Pixantrone, Guanfacine and Hydroxystilbamidine. These compounds, although not previously known as AChE inhibitors, represent diverse chemical classes including substituted thiophenes, pyridines, and fused nitrogen-containing heterocycles, showing high potential for treating neurodegenerative diseases such as Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders • Pain

Histidinol dehydrogenase (HisD): a critical regulator of Staphylococcus aureus virulence and a promising target for antivirulence therapy. (PubMed, Microbiol Spectr) - "HisD inhibition by pixantrone was further evaluated...By uncovering HisD's role in connecting metabolism to virulence through the saeR/S system, we reveal a druggable target for fighting multidrug-resistant infections. This work addresses the urgent need for innovative solutions to the global antibiotic resistance crisis, paving the way for therapies that outsmart evolving superbugs."

Journal • Hematological Disorders • Infectious Disease • Inflammation • GLS2 • IL6 • TNFA

Mechanism-informed identification of FDA-approved topoisomerase inhibitors disrupting SARS-CoV-2 nucleocapsid-RNA interactions. (PubMed, BMC Chem) - "Inspired by adenosine triphosphate (ATP)'s competitive inhibition of NP-RNA binding, we screened 121 FDA-approved ATP-competitive kinase inhibitors, identifying mitoxantrone (IC₅₀ = 1.22 µM) as a potent inhibitor. Considering its known topoisomerase inhibitory activity, we further screened 23 additional topoisomerase inhibitors, uncovering four active compounds-pixantrone (IC₅₀ = 5.67 µM), doxorubicin (IC₅₀ = 20.19 µM), epirubicin (IC₅₀ = 7.23 µM), and suramin (IC₅₀ = 0.44 µM)...Our findings demonstrate the feasibility of a mechanism-informed repurposing strategy and identify FDA-approved topoisomerase inhibitors and suramin as valuable chemical starting points. Although these compounds are not directly suitable as antivirals due to toxicity concerns, they provide promising scaffolds for further optimization aimed at selective disruption of SARS-CoV-2 NP-RNA interactions."

FDA event • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Nanoscopy Reveals Heparan Sulfate Clusters as Docking Sites for SARS-CoV-2 Attachment and Entry. (PubMed, bioRxiv) - "Blocking HS binding with the clinically used HS- binding agent pixantrone strongly inhibited the clinically relevant SARS-CoV-2 Omicron JN.1 subvariant from attaching to and infecting human airway cells...This new model suggests perturbation of HS binding as a more effective anti-COVID-19 strategy than previously recognized. It may apply broadly beyond COVID-19 because, analogous to SARS-CoV-2, HS binds many other viruses but is only considered an attachment regulator."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Evaluating the multitargeted potency of Pixuvri against cell cycle regulation proteins in cervical cancer. (PubMed, Front Oncol) - "Molecular dynamics (100 ns, NVT ensemble at 300K) validated stability by deviation and fluctuation studies and found many interactions to stabilize the complex, with binding free energy computations confirming its affinity. While the results support Pixuvri's repurposing for cervical cancer, experimental validation is essential for clinical application."

Journal • Cardiovascular • Cervical Cancer • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

PIXBRIDGE: Pixantrone as Bridging Therapy to Allogenic Transplant or CAR-T Cell Therapy in DLBCL Patients (clinicaltrials.gov) - P=N/A | N=15 | Active, not recruiting | Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

New trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Characterization of pixantrone regioisomeric conjugates arising from AP sites in DNA by NMR spectroscopy (ACS-Fall 2024) - "AP sites are reactive and recent studies showed they may form Schiff base conjugates with exocyclic amines on the anthracycline-class drugs pixantrone and mitoxantrone, analogs of the anti-tumor antibiotic doxorubicin. The two regioisomers are distinguished by NOESY NMR data. The NMR data also differential rates of formation of the two isomers favoring regioisomer A."

Oncology

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 • Oncology • Ovarian Cancer • Solid Tumor • MCM2

Interactions of pixantrone with apurinic/apyrimidinic sites in DNA. (PubMed, MicroPubl Biol) - "Here, pixantrone was demonstrated to have similar properties, but relative to mitoxantrone, it was significantly less potent in both DNA incision and APE1 inhibition. Consistent with these observations, pixantrone had ~ 15-fold lower affinity for DNA containing an AP site analogue, tetrahydrofuran, as measured by a Thiazole Orange (ThO) displacement assay."

Journal • Oncology

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 • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SMARCA2

Delineating Pixantrone Maleate's adroit activity against cervical cancer proteins through multitargeted docking-based MMGBSA, QM-DFT and MD simulation. (PubMed, PLoS One) - "We also explore the stability of the multitargeted potential of Pixantrone Maleate through 100ns MD simulations and investigate the RMSD, RMSF and intermolecular interactions between all three proteins-ligand complexes. All computational studies favour Pixantrone Maleate as a multitargeted inhibitor of the TBK1, DNA polymerase epsilon, and integrin α-V β-8 and can be validated experimentally before use."

Journal • Cervical Cancer • Oncology • Solid Tumor

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 • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • NOTCH1

PIVeR: Study of Pixantrone in CD20+ Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=74 | Active, not recruiting | Sponsor: The Lymphoma Academic Research Organisation | Recruiting ➔ Active, not recruiting

Enrollment closed • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Pharmacokinetic and Safety Study of Pixantrone in Patients With Metastatic Cancer and Hepatic Impairment (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: CTI BioPharma | N=32 ➔ 0 | Unknown status ➔ Withdrawn

Enrollment change • Metastases • Trial withdrawal • Hepatology • Oncology

Pixantrone (BBR 2778) in Patients With Refractory Acute Myelogenous Leukemia (AML) (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: CTI BioPharma | N=119 ➔ 12

Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Epcoritamab (Epkinly) for diffuse large B-cell lymphoma (DLBCL). (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Pixantrone as bridging therapy to allogeneic transplantation or in CAR T-cell pathway in patients with diffuse large B-cell lymphoma. (PubMed, Hematol Oncol) - No abstract available

CAR T-Cell Therapy • Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Insight into the structural effects of anthracycline drugs, pixantrone and mitoxantrone, in duplex DNA (ACS-Fall 2023) - "AP sites are reactive and recent studies showed they may form Schiff base conjugates with exocyclic amines on the anthracycline-class drugs pixantrone and mitoxantrone, analogs of the anti-tumor antibiotic doxorubicin. The hydroquinone moiety of mitoxantrone features two hydrogen bond donors, which may form two hydrogen bonds in the DNA duplex. The pixantrone, hydroquinone moiety features a nitrogen atom, which may only form one hydrogen bond as a hydrogen bond acceptor."

Oncology

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 • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD20 • NCF4 • NCOA3 • PLA2G2A