HLX22, an anti-HER-2 monoclonal antibody, in patients with advanced solid tumors overexpressing human epidermal growth factor receptor 2: an open-label, dose-escalation, phase 1 trial
AbstractHLX22 is a novel monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). This first-in-human, phase 1 dose-escalation study aimed to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HLX22 in patients with advanced solid tumors who had failed or were intolerant to standard therapies. Enrolled patients aged 18 to 75 years with histologically confirmed HER2-overexpressing advanced or metastatic solid tumors received intravenous HLX22 once every 3 weeks at 3, 10, and 25 mg/kg. Primary endpoints were safety and the maximum tolerated dose (MTD). Secondary endpo...
Source: Investigational New Drugs - May 4, 2023 Category: Drugs & Pharmacology Source Type: research
Prognosis prediction of icotinib as targeted therapy for advanced EGFR-positive non –small cell lung cancer patients
This study aimed to establish an effective scoring system to predict the one-year progression-free survival (PFS) of advanced NSCLC patients with EGFR mutations treated with icotinib as targeted therapy. A total of 208 consecutive patients with advanced EGFR-positive NSCLC treated with icotinib were enrolled in this study. Baseline characteristics were collected within 30 days before icotinib treatment. PFS was taken as the primary endpoint and the response rate as the secondary endpoint. Least absolute shrinkage and selection operator (LASSO) regression analysis and Cox proportional hazards regression analysis were used t...
Source: Investigational New Drugs - May 4, 2023 Category: Drugs & Pharmacology Source Type: research
Prospective role of liquid biopsy for early screening in laryngeal cancer
(Source: Investigational New Drugs)
Source: Investigational New Drugs - May 2, 2023 Category: Drugs & Pharmacology Source Type: research
Drug-drug interaction potential of SH-1028, a third-generation EGFR-TKI: in vitro and clinical trials
AbstractSH-1028 is an irreversible third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Considering the possibility of combination therapy in patients with NSCLC, we investigated the drug-drug interaction (DDI) potential of SH-1028 both in vitro and in clinical trials. The in vitro studies were conducted to determine the potential of SH-1028 as a substrate, inducer, or inhibitor of cytochrome P450 (CYP) subtypes. A phase I drug-drug interaction study in healthy volunteers was performed to evaluate the impact of co-administering ri...
Source: Investigational New Drugs - May 2, 2023 Category: Drugs & Pharmacology Source Type: research
Automated Radiosynthesis of 1 ‐(2‐[18F]Fluoroethyl)‐L‐Tryptophan ([18F]FETrp) for PET Imaging of Cancer in Humans
The radiotracer 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp or [18F]FETrp) is a substrate of indoleamine 2,3-dioxygenase (IDO), the initial and key enzyme of the kynurenine pathway associated with tumoral immune resistance. In preclinical PET studies, [18F]FETrp is highly accumulated in a wide range of primary and metastatic cancers, such as lung cancer, prostate cancer, and gliomas. However, the clinical translation of this radiotracer into the first-in-human trial has not been reported, partially due to its racemization during radiofluorination which renders the purification of the final product challenging. Howeve...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - April 29, 2023 Category: Biochemistry Authors: Huailei Jiang,
Yan Guo,
Hancheng Cai,
Nerissa Viola,
Anthony F. Shields,
Otto Muzik,
Csaba Juhasz Tags: RESEARCH ARTICLE Source Type: research
Liquid biopsy using cell-free DNA in the early diagnosis of hepatocellular carcinoma
AbstractHepatocellular carcinoma ranks fourth in cancer-related causes of death worldwide and second in China. Patients with hepatocellular carcinoma (HCC) at the early stage have a better prognosis compared to HCC patients at the late stage. Therefore, early screening for HCC is critical for clinical treatment decisions and improving the prognosis of patients. Ultrasound (US), computed tomography (CT), and serum alpha fetoprotein (AFP) have been used to screen HCC, but HCC is still difficult to be diagnosed in the early stage due to the low sensitivity of the above methods. It is urgent to find a method with high sensitiv...
Source: Investigational New Drugs - April 26, 2023 Category: Drugs & Pharmacology Source Type: research
Screening for Zika Virus in U.S. Armed Services Blood Program Donors: An Opportunity to Compare Emerging Infectious Disease Risk between the General U.S. Population and Military Donors
CONCLUSION: The study demonstrated the effectiveness of the cobas Zika test. DoD donors, who are included in emergency donor panels during military operations, were at no higher risk for Zika than the overall U.S. donor population. This article is protected by copyright. All rights reserved.PMID:37097201 | DOI:10.1111/trf.17375 (Source: Transfusion)
Source: Transfusion - April 25, 2023 Category: Hematology Authors: Chriselda G Fedyk George M Shahin Ronnie Hill Andrew P Cap DoD Zika IND Investigators Source Type: research
Screening for Zika Virus in U.S. Armed Services Blood Program Donors: An Opportunity to Compare Emerging Infectious Disease Risk between the General U.S. Population and Military Donors
CONCLUSION: The study demonstrated the effectiveness of the cobas Zika test. DoD donors, who are included in emergency donor panels during military operations, were at no higher risk for Zika than the overall U.S. donor population. This article is protected by copyright. All rights reserved.PMID:37097201 | DOI:10.1111/trf.17375 (Source: Transfusion)
Source: Transfusion - April 25, 2023 Category: Hematology Authors: Chriselda G Fedyk George M Shahin Ronnie Hill Andrew P Cap DoD Zika IND Investigators Source Type: research
Dasatinib in combination with BMS-754807 induce synergistic cytotoxicity in lung cancer cells through inhibiting lung cancer cell growth, and inducing autophagy as well as cell cycle arrest at the G1 phase
AbstractLung cancer is the leading cause of cancer-related deaths worldwide. Combination of drugs targeting independent signaling pathways would effectively block the proliferation of cancer cells with lower concentrations and stronger synergy effects. Dasatinib, a multi-targeted protein tyrosine kinase inhibitor targeting BCR-ABL and kinases of SRC family, has been successfully applied in the treatment of chronic myeloid leukemia (CML). BMS-754807, an inhibitor targeting the insulin-like growth factor 1 receptor (IGF-IR) and insulin receptor (IR) family kinases, has been in phase I development for the treatment of a varie...
Source: Investigational New Drugs - April 25, 2023 Category: Drugs & Pharmacology Source Type: research
A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition
Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of furthe r exploration. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 25, 2023 Category: Drugs & Pharmacology Source Type: research
Efficacy of salvage therapies after failure of adjuvant anti-PD-1 monotherapy for melanoma in the Chinese population: a multi-institutional cohort study
SummaryThe majority of melanoma patients experience relapse during adjuvant therapy or after the end of therapy. Sixty-one patients from 3 melanoma centres who experienced recurrence and received adjuvant pembrolizumab for resected stage III/IV melanoma were enrolled. Disease characteristics, recurrence characteristics, subsequent management and outcomes were retrospectively analysed. Sixty-one patients were enrolled in this study. The median time to first relapse from the commencement of adjuvant pembrolizumab was 8 months (1 –22 months). The first recurrences were locoregional alone in 25 patients (41%), distant alone ...
Source: Investigational New Drugs - April 24, 2023 Category: Drugs & Pharmacology Source Type: research
A dose escalation/expansion study evaluating dose, safety, and efficacy of the novel tyrosine kinase inhibitor surufatinib, which inhibits VEGFR 1, 2, & amp; 3, FGFR 1, and CSF1R, in US patients with neuroendocrine tumors
AbstractSurufatinib, is a potent inhibitor of vascular endothelial growth factor receptors 1 –3; fibroblast growth factor receptor-1; colony-stimulating factor 1 receptor. This Phase 1/1b escalation/expansion study in US patients with solid tumors evaluated 5 once daily (QD) surufatinib doses (3 + 3 design) to identify maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and evaluate safety and efficacy at the RP2D in 4 disease-specific expansion cohorts including pancreatic neuroendocrine tumors [pNET] and extrapancreatic NETs [epNET]. MTD and RP2D were 300 mg QD (escalation [n = 35]); 5 patients (15....
Source: Investigational New Drugs - April 19, 2023 Category: Drugs & Pharmacology Source Type: research
Soluble interleukin-2 receptor as a predictive biomarker for poor efficacy of combination treatment with anti-PD-1/PD-L1 antibodies and chemotherapy in non-small cell lung cancer patients
AbstractSoluble interleukin-2 receptor (sIL-2R) suppresses effector T-cells. Few studies have assessed serum sIL-2R in patients receiving immunotherapy. We evaluated the association between serum sIL-2R levels and the efficacy of anti-programmed cell death 1/ programmed death-ligand 1 (anti-PD-1/PD-L1) antibody combined with chemotherapy in non-small cell lung cancer (NSCLC) patients. We prospectively enrolled NSCLC patients who received anti-PD-1/PD-L1 antibody combined with platinum-based chemotherapy between 8/2019 and 8/2020 and measured their serum sIL-2R. The patients were divided into high and low sIL-2R groups base...
Source: Investigational New Drugs - April 14, 2023 Category: Drugs & Pharmacology Source Type: research
Brigatinib pharmacokinetics in patients with chronic hepatic impairment
SummaryBrigatinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment ofALK-positive non-small cell lung cancer. This open-label, parallel-group study investigated the effect of chronic hepatic impairment on the pharmacokinetics (PK) of brigatinib to inform dosing recommendations for these patients. Participants with hepatic impairment classified according to Child-Pugh categories of mild (A), moderate (B), or severe (C) and matched-healthy participants with normal hepatic function received a single oral dose of 90-mg brigatinib. Plasma samples were collected for the determination of brigatinib plas...
Source: Investigational New Drugs - April 13, 2023 Category: Drugs & Pharmacology Source Type: research
Targeting chemotherapy resistance in mesenchymal triple-negative breast cancer: a phase II trial of neoadjuvant angiogenic and mTOR inhibition with chemotherapy
(Source: Investigational New Drugs)
Source: Investigational New Drugs - April 12, 2023 Category: Drugs & Pharmacology Source Type: research
