Efficacy, safety, and cost-minimization analysis of axicabtagene ciloleucel and tisagenlecleucel CAR T-Cell therapies for treatment of relapsed or refractory follicular lymphoma
AbstractAxicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are chimeric antigen receptor (CAR) T-cell therapies used to treat adult patients with relapsed or refractory follicular lymphoma (rrFL) after two or more lines of systemic therapy. In the absence of head-to-head clinical trials, this study aimed to compare the efficacy, safety, and cost of axi-cel and tisa-cel in the treatment of rrFL after at least two lines of treatment. Overall response rate (ORR) and safety signals were compared using reporting odds ratios (RORs) with 95% confidence intervals (CIs) at p < 0.05. Progression-free survival...
Source: Investigational New Drugs - August 12, 2023 Category: Drugs & Pharmacology Source Type: research
Cytotoxicity of poly-guanidine in medulloblastoma cell lines
SummaryMedulloblastoma (MB) is the most common pediatric brain tumor. The therapy frequently causes serious side effects, and new selective therapies are needed. MB expresses hyper sialylation, a possible target for selective therapy. The cytotoxic efficacy of a poly guanidine conjugate (GuaDex) incubated with medulloblastoma cell cultures (DAOY and MB-LU-181) was investigated. The cells were incubated with 0.05–8 µM GuaDex from 15 min to 72 h. A fluorometric cytotoxicity assay (FMCA) measured the cytotoxicity. Labeled Gu aDex was used to study tumor cell interaction. FITC-labelSambucus nigra confirmed high express...
Source: Investigational New Drugs - August 9, 2023 Category: Drugs & Pharmacology Source Type: research
Lurbinectedin in patients with pretreated endometrial cancer: results from a phase 2 basket clinical trial and exploratory translational study
In conclusion, considering the exploratory aim of this trial and the hints of antitumor activity observed together with a predictable and manageable safety profile, further biomarker-based development of lurbinectedin is recommended in this indication in combination with other agents.Clinicaltrials.gov identifier: NCT02454972. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 9, 2023 Category: Drugs & Pharmacology Source Type: research
Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease
This study evaluated the efficacy of intracerebroventricular (ICV) delivery of an adeno-associated viral vector encoding ovine CLN5 (scAAV9/oCLN5) in a naturally occurring sheep model of CLN5 disease. CLN5 affected (CLN5−/−) sheep received low, moderate, or high doses of scAAV9/oCLN5 at three disease stages. The treatment delayed disease progression, extended survival and slowed stereotypical brain atrophy in most animals. Of note, one high dose treated animal only developed mild disease symptomology and survived to 60.1 months of age, triple the natural life expectancy of an untreated CLN5−/− sheep. Eyesight was n...
Source: Frontiers in Genetics - August 8, 2023 Category: Genetics & Stem Cells Source Type: research
Enhanced antitumor and anti-metastasis by VEGFR2-targeted doxorubicin immunoliposome synergy with NK cell activation
SummaryLiposomal doxorubicin exhibits stronger drug accumulation at the tumor site due to the Enhanced Permeability and Retention (EPR) effect. However, the prognosis for the patient is poor due to this drug ’s lack of targeting and tumor metastasis during treatment. Vascular epidermal growth factor receptor (VEGFR2) plays an important role in angiogenesis and cancer metastasis. To enhance antitumor efficacy of PEGylated liposomal doxorubicin, we constructed a VEGFR2-targeted and doxorubicin-loaded im munoliposome (Lipo-DOX-C00) by conjugating a VEGFR2-specific, single chain antibody fragment to DSPE-PEG2000-MAL, and the...
Source: Investigational New Drugs - August 5, 2023 Category: Drugs & Pharmacology Source Type: research
Development and characterization of fused human arginase I for cancer therapy
In this study, we described the generation and characterization of a fused human arginase I variant (FHA-3) having improved circulatory half-life. FHA-3 protein was engineered by fusing rhArg I with a half-life extension partner (domain of human serum albumin) via a peptide linker and was produced usingP. pastoris expression system. This purified biopharmaceutical (FHA-3) exhibits (i) increased arginine-hydrolyzing activity in buffer, (ii) cofactor - independency, (iii) increased circulatory half-life (t1/2) and (iv) potent anti-cancer activity against human cancer cell lines under in vitro and in vivo conditions. (Source:...
Source: Investigational New Drugs - August 3, 2023 Category: Drugs & Pharmacology Source Type: research
Development of novel palbociclib-based CDK4/6 inhibitors exploring the back pocket behind the gatekeeper
SummaryCDK4/6 inhibitors plus endocrine therapy is a standard therapy for HR+/HER2- breast cancer. Herein, using structure-based drug design strategy, a novel series of palbociclib derivatives were designed and synthesized as CDK4/6 inhibitors, among which compound17m exhibited more potent CDK4/6 inhibitory activity and in vitro antiproliferative activity against the phosphorylated Rb-positive cell line MDA-MB-453 than the approved drug palbociclib. Moreover, compound17m possessed remarkable CDK4/6 selectivity over other CDK family members including CDK1, CDK2, CDK3, CDK5, CDK7 and CDK9. The potent and selective CDK4/6 inh...
Source: Investigational New Drugs - July 20, 2023 Category: Drugs & Pharmacology Source Type: research
Pharmacological assessment of the antineoplastic and immunomodulatory properties of a new spiroindolone derivative (7 ’,8’-Dimethoxy-1’,3’-dimethyl-1,2,3’,4’-tetrahydrospiro[indole-3,5’-pyrazolo[3,4-c]isoquinolin]-2-one) in chronic myeloid leukemia
In conclusion, the spiroindolone-derived compound evaluated in this study has demonstrated significant potential as a therapeutic agent for the treatment of chronic myeloid leukemia. Further investigations are warranted to explore its clinical applications. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 15, 2023 Category: Drugs & Pharmacology Source Type: research
Idarubicin versus epirubicin in drug-eluting beads-transarterial chemoembolization for treating hepatocellular carcinoma: A real-world retrospective study
Summary
The purpose of this study was to compare the efficacy and safety of idarubicin-loaded drug-eluting beads-transarterial chemoembolization (IDA-TACE) and epirubicin-loaded drug-eluting beads-TACE (EPI-TACE) in treating hepatocellular carcinoma (HCC).
All patients with HCC treated with TACE in our hospital between June 2020 and January 2022 were screened. The included patients were divided into the IDA-TACE group and EPI-TACE group to compare overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events.
There were 55 patients each in the IDA-TACE and EPI-TACE groups. Com...
Source: Investigational New Drugs - July 12, 2023 Category: Drugs & Pharmacology Source Type: research
Indirect comparisons of efficacy of zanubrutinib versus orelabrutinib in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or relapsed or refractory mantle cell lymphoma
SummaryWe conducted two indirect comparisons to estimate the efficacy of zanubrutinib versus orelabrutinib in Chinese patients with relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or R/R mantle cell lymphoma (MCL). An unanchored matching-adjusted indirect comparison (MAIC) was performed in R/R CLL/SLL patients. Individual patient data from zanubrutinib trial (BGB-3111-205) were adjusted to match the aggregated data from the orelabrutinib trial (ICP-CL-00103). A na ïve comparison was performed in R/R MCL for the different response assessment methodology and efficacy analysis s...
Source: Investigational New Drugs - July 8, 2023 Category: Drugs & Pharmacology Source Type: research
Assessment of the potential of the MET inhibitor tepotinib to affect the pharmacokinetics of CYP3A4 and P-gp substrates
SummaryTepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer harboringMET exon 14 skipping alterations. The aims of this work were to investigate the potential for drug-drug interactions via cytochrome P450 (CYP) 3A4/5 or P-glycoprotein (P-gp) inhibition. In vitro studies were conducted in human liver microsomes, human hepatocyte cultures and Caco-2 cell monolayers to investigate whether tepotinib or its major metabolite (MSC2571109A) inhibited or induced CYP3A4/5 or inhibited P-gp. Two clinical studies were conducted to i...
Source: Investigational New Drugs - July 6, 2023 Category: Drugs & Pharmacology Source Type: research
The p53 reactivator PRIMA-1MET synergises with 5-fluorouracil to induce apoptosis in pancreatic cancer cells
This study involved p53-mutant (AsPC-1) and p53-wild type (Capan-2) PC cell lines. The cytotoxicity of PRIMA-1MET alone or in combination with 5-FU was evaluated by MTT assay. Synergism was assessed by calculating the combination index (CI) via CalcuSyn software. Fluorescence microscopy was used to analyse apoptosis following acridine orange/ethidium bromide (AO/EB) staining. Morphological changes were investigated with an inverted microscope. Quantitative reverse transcription PCR (RT ‒qPCR) was used to measure gene expression. Both PC cell lines were sensitive to PRIMA-1MET monotherapy. Furthermore, PRIMA-1MET and 5-FU...
Source: Investigational New Drugs - July 4, 2023 Category: Drugs & Pharmacology Source Type: research
High-Content Small Molecule Screen Identifies a Novel Compound That Restores AP-4-Dependent Protein Trafficking in Neuronal Models of AP-4-Associated Hereditary Spastic Paraplegia
In this study, we developed a high-throughput screening assay to identify molecules that correct aberrant protein trafficking in adaptor protein complex 4 (AP-4) deficiency, a rare but prototypical form of childhood-onset hereditary spastic paraplegia, characterized by mislocalization of the autophagy protein ATG9A. Using high-content microscopy and an automated image analysis pipeline, we screened a diversity library of 28,864 small molecules and identified a lead compound, C-01 , that restored ATG9A pathology in multiple disease models, including patient-derived fibroblasts and induced pluripotent stem cell-derived neuro...
Source: Cell Research - July 3, 2023 Category: Cytology Authors: Afshin Saffari Barbara Brechmann Cedric Boeger Wardiya Afshar Saber Hellen Jumo Dosh Whye Delaney Wood Lara Wahlster Julian Alecu Marvin Ziegler Marlene Scheffold Kellen Winden Jed Hubbs Elizabeth Buttermore Lee Barrett Georg Borner Alexandra Davies Musta Source Type: research
Hybrid 18F-Fluoroethyltyrosine PET and MRI with Perfusion to Distinguish Disease Progression from Treatment-Related Change in Malignant Brain Tumors: The Quest to Beat the Toughest Cases
Conclusion: Hybrid 18F-FET PET/MRI positively impacted the routine clinical care of challenging malignant brain tumor cases at a U.S. institution. The results add to a growing body of literature that 18F-FET PET complements MRI, even rescuing MRI when it fails. (Source: Journal of Nuclear Medicine)
Source: Journal of Nuclear Medicine - June 30, 2023 Category: Nuclear Medicine Authors: Smith, N. J., Deaton, T. K., Territo, W., Graner, B., Gauger, A., Snyder, S. E., Schulte, M. L., Green, M. A., Hutchins, G. D., Veronesi, M. C. Tags: Clinical Investigations Source Type: research
Safety and efficacy of immunotherapy plus chemotherapy as neoadjuvant treatment for patients with locally advanced gastric cancer: a retrospective cohort study
Conclusions: PD-1 inhibitors plus chemotherapy demonstrated promising efficacy, with encouraging pCR and survival outcomes in a neoadjuvant setting for patients with LAGC. The combined therapy also showed a good safety profile. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 27, 2023 Category: Drugs & Pharmacology Source Type: research
