Miripla (miriplatin) / Sumitomo Pharma - LARVOL DELTA

Clinical insight-driven micron-sized cholesterol oxidation platform for membrane lipid therapy of advanced ovarian cancer. (PubMed, J Nanobiotechnology) - "Subsequently, a novel cholesterol oxidation-mediated membrane lipid therapy employing PLGA microspheres co-loaded with miriplatin (MiR) and cholesterol oxidase (COD) was proposed for drug-resistant advanced ovarian cancer therapy...More importantly, PLGA encapsulation significantly decreased the toxic side effects associated with continuous platinum-based chemotherapy. Overall, cholesterol oxidation-mediated membrane lipid therapy represented a promising approach for treating advanced ovarian cancer."

Journal • Oncology • Ovarian Cancer • Solid Tumor

Transarterial Chemoembolization for Patients With Hepatocellular Carcinoma Using Miriplatin Without the Need for Hydration. (PubMed, Clin Transl Sci) - "The median survival time was 1490 days for the miriplatin group and 1,830 days for the cisplatin group (p = 0.4022; ratio = 0.814; 95% confidence interval 0.546-1.215). In conclusion, miriplatin will benefit patients with HCC who cannot tolerate perioperative hydration."

Journal • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor

A fluorinated prodrug strategy enhances the therapeutic index of nanoparticle-delivered hydrophilic drugs. (PubMed, Colloids Surf B Biointerfaces) - "Additionally, these optimized prodrugs significantly amplified miriplatin's stemness-suppressing activity...This formulation exhibited targeted action against CTCs, effectively preventing postoperative metastasis in a breast cancer mouse model and significantly improving survival rates in treated mice. In conclusion, the fluorinated aromatic prodrug strategy offers a promising method for optimizing hydrophilic small-molecule drugs, enhancing their druggability, and preventing postoperative metastasis."

Journal • Breast Cancer • Oncology • Solid Tumor • CTCs

An experimental study on the diagnostic advantage of dual-energy computed tomography over single-energy scan to evaluate the treatment effect following transcatheter arterial chemoembolization. (PubMed, PLoS One) - "More accurate and quantitative lipiodol evaluation in targeted tumors after TACE can be achieved by applying DECT rather than SECT."

Journal • Oncology

Metal complex lipid-based nanoparticles deliver metabolism-regulating lomitapide to overcome CTC immune evasion via activating STING pathway. (PubMed, Eur J Pharm Biopharm) - "This design includes MCL-miriplatin to increase NP stiffness and loads lomitapide (lomi) modulating cholesterol levels, resulting in the creation of PLTs@Pt-lipid@lomi NPs. Ultimately, PLTs@Pt-lipid@lomi NPs reduce metastasis in a post-surgery animal model. While cholesterol-regulating agents are limited in efficacy when being repositioned as immunomodulatory agents, this MCL-composing NP strategy demonstrates the potential to effectively deliver these agents to target CTC clusters."

Journal • Oncology

Matinas BioPharma Reports First Quarter 2024 Financial Results and Provides a Business Update (GlobeNewswire) - "LNC Platform Update....A new formulation of LNC-miriplatin, an insoluble platinum chemotherapeutic approved in Japan for hepatocellular carcinoma has been developed. In vitro testing demonstrated strong cellular uptake and tumor cell-killing capabilities. Next steps are to assess the formulation in vivo. LNC-miriplatin would be the second cancer agent successfully formulated with LNCs."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Lipid core-shell nanoparticles co-deliver FOLFOX regimen and siPD-L1 for synergistic targeted cancer treatment. (PubMed, J Control Release) - "FOLFOX regimen, composed of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (OXP), has been used as clinical standard therapeutic regimen in treatments of colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC)...Herein, a lipid core-shell nanoparticle codelivery platform was designed for simultaneous encapsulation of variant FOLFOX composed of miriplatin (MiPt), 5-Fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), calcium folinate (CF) and PD-L1 siRNA (siPD-L1) with high efficiencies, and their synergistic anti-tumor mechanisms were studied, respectively...CF worked as the sensitizer of FdUMP. The enhanced long-term anti-tumor effect of the prepared "all-in-one" formulation compared to free drug regimen and other controls, was verified in heterotopic CRC mice models and ESCC mice models, providing new thoughts for researchers and showing a promising prospect of translation into clinical applications."

Journal • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • PD-L1

Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication. (PubMed, Acta Pharm Sin B) - "Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CAV1 • TFAM

Enhanced binding of β-catenin and β-TrCP mediates LMPt's anti-CSCs activity in colorectal cancer. (PubMed, Biochem Pharmacol) - "Here, we report a liposome loaded with low toxicity and high effectiveness of miriplatin, lipo-miriplatin (LMPt) with high miriplatin loading, and robust stability, exhibiting a superior inhibitory effect on CSCs and non-CSCs. LMPt predominantly inhibits the survival of oxaliplatin-resistant (OXA-resistant) cells composed of CSCs...Further studies revealed that the strengthened binding of β-catenin and β-TrCP initiates ubiquitination and degradation of β-catenin induced by LMPt. In addition,the Apctransgenicmouse model, in which colon tumors are spontaneously formed, demonstrates LMPt's potent anti-non-CSCs activity in vivo."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CTNNB1 • NANOG • POU5F1

Transcatheter arterial chemoembolization for hepatocellular carcinoma in super-elderly patients aged ≥ 85 years (SIR 2023) - " TACE using powdered cisplatin without Lipiodol, epi- rubicin –Lipiodol emulsion, miriplatin –Lipiodol suspension, and drug-eluting beads were performed in 11, 20, 15, and 9 cases, respectively. Transcatheter arterial chemoembolization for hepa- tocellular carcinoma in super-elderly patients aged /C2185 years may be safe and acceptable."

Clinical • Gastrointestinal Cancer • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Pain • Solid Tumor

Combination Therapy by Transarterial Injection of Miriplatin-Iodized Oil Suspension with Microwave Ablation for Medium-Sized Hepatocellular Carcinoma: the Preliminary Experience. (PubMed, Interv Radiol (Higashimatsuyama)) - "No local tumor progression was observed during the follow-up period (mean 12.0 ± 2.0 months, range 2.7-23.9 months). Miriplatin-iodized oil suspension-microwave ablation for medium-sized hepatocellular carcinomas can be safely performed with good local control."

Combination therapy • Journal • Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Oncology • Respiratory Diseases • Solid Tumor

A chemical perspective on the clinical use of platinum-based anticancer drugs. (PubMed, Dalton Trans) - "Since then, carboplatin and oxaliplatin have been approved world-wide and nedaplatin, lobaplatin, heptaplatin, dicycloplatin, and miriplatin have been approved in individual countries...Cisplatin is typically formulated in saline-based solutions while carboplatin and oxaliplatin are formulated in dextrose...As cancer is predominantly a disease of old age, many cancer patients who are administered a platinum drug may have other medical conditions which means they may also be taking many non-cancer medicines. The co-administration of non-cancer medicines to patients can potentially affect the efficacy of platinum drugs and/or change the severity of their side effects through drug-drug interactions."

Journal • Review • Oncology

Promoted antitumor therapy on pancreatic cancer by a novel recombinant human albumin-bound miriplatin nanoparticle. (PubMed, Eur J Pharm Sci) - "In vitro, the half-maximal inhibitory concentration (IC) of rHSA-miPt was 12.7 μM vs more than 100 μM of gemcitabine (Gem). Compared with Gem, rHSA-miPt was identified to be safer and less toxic based on body weight loss in mice (0% vs 20%), the survival rate of mice (100% vs 80%) and hematological and biochemical parameters of the mice including leukocytes, lymphocytes, neutrophils, monocytes, serum alanine aminotransferase and aspartate aminotransferase. The present study revealed that rHSA-miPt might be a promising candidate for pancreatic cancer therapy."

Journal • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Regorafenib-loaded poly (lactide-co-glycolide) microspheres designed to improve transarterial chemoembolization therapy for hepatocellular carcinoma. (PubMed, Asian J Pharm Sci) - "Transarterial chemoembolization (TACE) has been widely introduced to treat hepatocellular carcinoma (HCC) especially for unresectable patients for decades. In vivo anti-tumor efficacy was further determined in HepG2 xenograft tumor mouse model, demonstrating that REGO microspheres could improve the antitumor efficacy of miriplatin remarkably compared with miriplatin monotherapy. In conclusion, the obtained REGO microspheres demonstrated promising therapeutic effects against HCC when combined with TACE."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

Combination therapy by transarterial injection of miriplatin-iodized oil suspension with radiofrequency ablation (RFA) versus microwave ablation (MWA) for small hepatocellular carcinoma: a comparison of therapeutic efficacy. (PubMed, Jpn J Radiol) - "MPT-MWA may have improved therapeutic efficiency in the treatment of small HCCs."

Clinical • Combination therapy • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

Nanoparticle-delivered miriplatin ultrasmall dots suppress triple negative breast cancer lung metastasis by targeting circulating tumor cells. (PubMed, J Control Release) - "It was found that uPtDs NPs displayed a superior DNA damage capability via enhanced-interactions with DNA and a significantly stronger effect in reducing CSC-like property of TNBC cells, compared to conventional cisplatin and miriplatin. Given the desired-safety profile of miriplatin, the uPtDs represent a promising therapeutic agent of the metal-based nanomedicines to reduce cancer metastasis. SIGNIFICANCE: The miriplatin ultrasmall dots developed from clinically-prescribed miriplatin may serve as a potent systemically-administered agent to target CTCs and reduce cancer metastasis."

Journal • Breast Cancer • Gastrointestinal Cancer • Hepatology • Liver Cancer • Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTCs • ITGA5

In vivo evaluation of a monodisperse solid-in-oil-in-water miriplatin/ lipiodol emulsion in transcatheter arterial chemoembolization using a rabbit VX2 tumor model. (PubMed, PLoS One) - "The results show that Lipiodol accumulation and retention in VX2 tumor can possibly be improved with a monodisperse emulsion; however, it should be verified with a larger study. Moreover, no significant adverse events are associated with the use of the emulsion."

Journal • Preclinical • Gastroenterology • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma. (PubMed, J Gastroenterol) - "Miriplatin plus irradiation had synergistic anti-tumor activity on HCC cells through PUMA-mediated apoptosis and cell cycle arrest. This combination may possibly be effective in treating locally advanced HCC."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • TP53

Transcatheter arterial chemotherapy with miriplatin for patients with hepatocellular carcinoma and chronic renal failure (Nihon Shokakibyo Gakkai Zasshi) - P=NA, N=67; Estimated GFR within 2 months after miriplatin administration did not decrease significantly by Wilcoxon signed rank test (pretreatment: 46ml/min, 1 month: 48ml/min, p=0.019, 2 months: 45ml/min, p=0.619) (p<0.003 was significant by the Bonferroni correction); CR in terms of tumor necrosis was achieved in 14 of 67 pts & no serious AEs were observed

Retrospective data • Hepatocellular Cancer • None

Database analysis of patients with hepatocellular carcinoma and treatment flow in early and advanced stages. (PubMed, Pharmacol Res Perspect) - "Epirubicin was the most frequently (44.1%) used chemotherapeutic agent for first-line TACE, followed by miriplatin (23.6%) and cisplatin (12.3%)...Sorafenib was used concomitantly for first-line TACE in 3.2% of patients, and its use increased significantly in advanced stages. Clear differences in baseline characteristics and treatment flow between early and advanced stages were identified. Continuous analysis of the database with longer follow-up may provide useful information about treatment selection and prediction of outcome such as survival."

Clinical • Journal • Cardiovascular • Diabetes • Dyslipidemia • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Hepatitis C Virus • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Liver Cancer • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial. (PubMed) - BMC Cancer - "The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve."

Journal • Biosimilar • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Venous Thromboembolism

Therapeutic efficacy of miriplatin in combination with radiotherapy for advanced hepatocellular carcinoma (JSMO 2019) - No abstract available.

Clinical • Combination therapy

Acute Exacerbation of Idiopathic Interstitial Pneumonia in a Patient with Hepatocellular Carcinoma after Transcatheter Arterial Therapy Using Miriplatin. (PubMed, Intern Med) - "Chest computed tomography revealed extensive ground-glass opacity and traction bronchiectasis in bilateral lung fields; subsequently, she was diagnosed with AE-IIP triggered by transcatheter arterial therapy using miriplatin. Despite systemic administration of high-dose corticosteroid and cyclophosphamide, she died of respiratory failure on day 36."

Clinical • Journal

Therapeutic Efficacy of Chemoradiotherapy with Miriplatin for Hepatocellular Carcinoma (DDW 2019) - "Recently, therapeutic efficacy of combination with radiation and CDDP for advanced HCC has been reported. CONCLU- SION Our data suggested that the combination with MPT and radiation showed their synergistic effect on apoptosis induction in HCC cells and that PUMA played an important role in apoptosis. Our results also suggest that combination with MPT and radiation is effective and safe, and is a promising treatment strategy for advanced HCC."

Clinical • PARP Biomarker