Safety and blood levels of daratumumab after switching from intravenous to subcutaneous administration in patients with multiple myeloma
In this study, we investigated the safety and blood levels of daratumumab after switching from IV to SC in patients with multiple myeloma (MM). Patients who switched from IV to SC of daratumumab between June 2021 and May 2022 at Kobe City Medical Center General Hospital were included in the study. Blood daratumumab levels were measured using liquid chromatography-tandem mass spectrometry. Safety after switching from IV to SC was evaluated for six months and graded according to the Common Terminology Criteria for Adverse Events, version 5.0. The median body weight of ten patients included in the analysis was 57.4 kg (rang...
Source: Investigational New Drugs - September 18, 2023 Category: Drugs & Pharmacology Source Type: research
A novel anticancer quinolone, (R)-WAC-224, has anti-leukemia activities against acute myeloid leukemia
This study evaluated the anti-leukemia potential ofR-WAC or racemic WAC-224 (WAC) in vitro and in vivo. R-WAC significantly inhibited the human AML cell line proliferation (MV4-11, HL60, and KG1a), which was comparable to daunorubicin and cytarabine, not affected by P-glycoprotein overexpression. WAC did neither increase serum troponin-T nor decrease the crypt numbers in the small intestine, indicating WAC was less toxic than doxorubicin.R-WAC monotherapy demonstrated prolonged survival in the AML mice model and inhibited tumor growth in the MV4-11 xenograft mice model. Moreover, the combination ofR-WAC and cytarabine demo...
Source: Investigational New Drugs - September 13, 2023 Category: Drugs & Pharmacology Source Type: research
A novel bivalent anti-c-MET/PD-1 bispecific antibody exhibits potent cytotoxicity against c-MET/PD-L1-positive colorectal cancer
In this study, in addition to the tumor intrinsic mechanism investigation with molecular biology assay in vitro, a humanized mouse model was used to evaluate antitumor activity of the BsAbin vivo. The BsAb could inhibit c-MET/PD-L1+ CRC cell migration and show strong antitumor activity against HCT116 tumors in mice, potentially by inducing the degradation of c-MET protein in a dose and time-dependent manner. The BsAb could suppress the phosphorylation of c-MET downstream proteins GRB2-associated-binding protein 1 (Gab1) and focal adhesion kinase (FAK). Considering the tumor extrinsic mechanism, the BsAb may promote phagocy...
Source: Investigational New Drugs - August 30, 2023 Category: Drugs & Pharmacology Source Type: research
The efficacy and safety of selective RET inhibitors in RET fusion-positive non-small cell lung cancer: a meta-analysis
Conclusions Selective RET inhibitors Pralsetinib and Selpercatinib have shown a good effect on RET fusion-positive NSCLC, with a low incidence of adverse events. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 21, 2023 Category: Drugs & Pharmacology Source Type: research
Early on-treatment C-reactive protein and its kinetics predict survival and response in recurrent and/or metastatic head and neck cancer patients receiving first-line pembrolizumab
Conclusion: On-treatment CRP was identified as a prognostic biomarker for objective response and survival in R/M HNSCC patients receiving first-line pembrolizumab and could be easily incorporated into clinical practice as a widely avai lable and cost-effective biomarker. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 21, 2023 Category: Drugs & Pharmacology Source Type: research
Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma
SummaryImmune-related liver injuries are closely associated with the liver ’s fundamental state. Patients with advanced biliary tract carcinoma (BTC) have poor liver function. We evaluated the clinical data of immune-related liver injury in patients with advanced BTC and gastric cancer (GC) during immune checkpoint inhibitor (ICI) treatment between February 2019 and July 2022 at Peking University First Hospital. Twenty-five patients with advanced BTC were identified. Fifteen patients (60%) experienced immune-related liver injury during ICI treatment. We also evaluated the clinical status of patients with GC in another gr...
Source: Investigational New Drugs - August 17, 2023 Category: Drugs & Pharmacology Source Type: research
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
Preclinical evaluation of the VEGF/Ang2 bispecific nanobody BI 836880 in nasopharyngeal carcinoma models
This study showed that BI 836880 has anti-proliferative, anti-angiogenic and possibly immunomodulatory effect in clinical models of NPC, therefore the dual targeting of VEGF and Ang2 signaling in NPC should be further investigated. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 12, 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
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
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
