455PDFirst-in-human, first-in-class phase I study of MTL-CEBPA, a RNA oligonucleotide targeting the myeloid cell master regulator C/EBP- α, in patients with advanced hepatocellular cancer (HCC)

AbstractBackgroundMTL-CEBPA is a first-in-class small activating RNA (saRNA) oligonucleotide which specifically up-regulates the myeloid cell master regulator, C/EBP- α (CCAAT/enhancer-binding protein alpha).MethodsWe conducted a phase I, 3  + 3 dose escalation and dose expansion trial of MTL-CEBPA in adults with HCC or secondary liver cancer. Patients received intravenous MTL-CEBPA at 28-160 mg/m2 for 3 weeks either QW, BIW at d1 and d2, BIW at d1 and d3, or TIW at d1, d2, and d3 followed by a rest period of 1 week. Adverse even ts (AEs), serum PK, WBC biomarkers and anti-tumour activity were assessed.Results38 participants (31 HCC, 4 colorectal, 2 fibrolamellar, 1 ampullary) have been treated across 6 dose levels (28-160  mg/m2) and 3 dosing schedules: 29M/9F, median age 66 years (range 27 - 80), ECOG PS 0/1: 16/22. In 28 HCC patients evaluable for efficacy, PR was achieved in 1 pt, SD >  1 year in 1 patient and SD 
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research

Related Links:

AbstractBackgroundWithin the context of metastatic colorectal cancer, patients with Eastern Cooperative Oncology Group (ECOG) performance score 0 –1 are usually pooled together in clinical practice guidelines and clinical trials’ reports. The current study aims to delineate potential differences in outcomes between metastatic colorectal cancer patients with ECOG score 0 versus 1 who are treated with currently accepted first-line fluoroura cil (5FU)-based chemotherapy.MethodsThe current study is based on a pooled dataset from five clinical trials of 5FU-based treatment for metastatic colorectal cancer (NCT002720...
Source: International Journal of Colorectal Disease - Category: Gastroenterology Source Type: research
Publication date: Available online 11 November 2019Source: Blood Cells, Molecules, and DiseasesAuthor(s): Jana Volejnikova, Petr Vojta, Helena Urbankova, Renata Mojzíkova, Monika Horvathova, Ivana Hochova, Jaroslav Cermak, Jan Blatny, Martina Sukova, Eva Bubanska, Jaroslava Feketeova, Daniela Prochazkova, Julia Horakova, Marian Hajduch, Dagmar PospisilovaAbstractDiamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia, underlied by haploinsufficient mutations in genes coding for ribosomal proteins (RP) in approximately 70% of cases. DBA is frequently associated with somatic malformations, endocrine dysfu...
Source: Blood Cells, Molecules, and Diseases - Category: Hematology Source Type: research
Conclusions This study did not achieve its primary objective of establishing an RP2D of combination prexasertib + ralimetinib that could be safely administered to patients with advanced cancer.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
AbstractBackgroundElevated microsatellite alterations at selected tetranucleotides (EMAST) is a poorly investigated form of microsatellite instability (MSI) in colorectal cancer (CRC).ObjectiveThe aim of this study was to investigate the clinicopathological features of EMAST in CRC and its relation to outcome.MethodsA population-based, consecutive cohort of surgically treated stage I –III CRC patients investigated for high-frequency MSI (MSI-H) and EMAST. Clinicopathological differences were reported as odds ratios (OR) and survival was presented as hazard ratios (HR) with 95% confidence intervals (CIs).ResultsOf 161...
Source: Annals of Surgical Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsIn this Phase 2 KSCC 1602 trial of bevacizumab plus FTD/TPI, the primary endpoint of PFS was achieved. This combination therapy showed favorable survival outcomes with an acceptable safety profile for elderly patients with previously untreated metastatic colorectal cancer.Clinical trial identificationUMIN000025241.Legal entity responsible for the studyKyushu Study group of Clinical Cancer.FundingTaho Pharmaceutical.DisclosureA. Makiyama: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lily Pharmaceutical; Speaker Bureau / Expert testimony: Chugai Pharmaceutical; Speaker Bureau / Expert testimony: ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsPembro in combination with mFOLFOX7 or FOLFIRI was safe and tolerable in patients with mCRC.Clinical trial identificationNCT03374254; Release date: December 15, 2017.Editorial acknowledgementJacqueline Kolston, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA); Funded by Merck Sharp&Dohme Corp., a subsidiary of Merck&Co., Inc., Kenilworth, NJ, USA.Legal entity responsible for the studyMerck Sharp&Dohme Corp., a subsidiary of Merck&Co., Inc., Kenilworth, NJ, USA, and Array BioPharma.FundingMerck Sharp&Dohme Corp., a subsidiary of Merck&Co., Inc., Kenilworth, NJ, USA, and Array Bi...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsIntravenous administrations of ISU104 were well tolerated up to 20  mg/kg/day without DLT, and showed disease control rate of 60.0%. Safety and efficacy of ISU104 as mono- or combination-therapy and potential biomarkers will be further explored in head and neck, colorectal and breast cancers.Clinical trial identificationNCT03552406.Legal entity responsible for the studyISU Abxis.FundingKDDF: Korea Drug Development Fund.DisclosureB. Keam: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Genexin; Research grant / Funding (self): ONO; Research grant / Funding (self): ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundThe KRASG12C mutation occurs in ∼13% of lung cancers (11% of non-small cell lung cancer [NSCLC]), 3% of colorectal cancer (CRC) and appendix cancers, and 1–3% of other solid tumors. KRASG12C is a driver of tumorigenesis, but there are no approved therapies targeting this mutation. AMG 510, a novel, orally administered small molecule, specifically and irreversibly inhibits KRASG12C by locking it in an inactive GDP-bound state. A phase 1, first-in-human, open-label, multicenter study is underway to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510 in adult patients ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThe oral small molecule AXL kinase inhibitor TP-0903 is well tolerated with a manageable safety profile. Hematologic toxicity was observed as a DLT. Future studies will evaluate the role of TP0903 in selected disease cohorts as monotherapy and in combination. Serum soluble AXL will be evaluated as a potential predictive biomarker of response.Clinical trial identificationNCT: 02729298.Legal entity responsible for the studyTolero Pharmaceuticals, Inc.FundingTolero Pharmaceuticals, Inc.DisclosureJ. Sarantopoulos: Research grant / Funding (institution): Tolero. G. Fotopoulos: Research grant / Funding (institution): ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThis is the first study evaluating a PRMT5 inhibitor. Overall, AEs were common but manageable. Patients with multiple tumor types responded to therapy. Part 2 of the study is open for subjects with predefined solid tumors and non-Hodgkin ’s lymphoma.Clinical trial identificationNCT02783300.Legal entity responsible for the studyGlaxoSmithKline.FundingGlaxoSmithKline.DisclosureL.L. Siu: Advisory / Consultancy: Merck (compensated), Pfizer (compensated), Celgene (compensated), AstraZeneca/Medimmune (compensated), Morphosys (compensated), Roche (compensated), GeneSeeq (compensated), Loxo (compensated), Oncorus ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
More News: Allergy & Immunology | Anemia | Bilirubin | Cancer | Cancer & Oncology | Clinical Trials | Colorectal Cancer | Genetics | Grants | Legislation | Liver | Study | Urology & Nephrology