Safety and efficacy of apatinib in combination with chemotherapy with or without immunotherapy versus chemotherapy alone as first-line treatment for advanced gastric cancer
The objective response rate (ORR) of the combination treatment group was 65.9%, and 36.8% in the simple chemotherapy group. Statistically significant differences are shown (P = 0.014). No serious (Grade IV) adverse events occurred in either group. Our study indicates that apatinib in combination with chemotherapy with or without immunotherapy as first-line treatment for advanced GC exhibits good anti-tumor activity and is well tolerated by patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 17, 2024 Category: Drugs & Pharmacology Source Type: research
PD-1 inhibitor combined with albumin paclitaxel and apatinib as second-line treatment for patients with metastatic gastric cancer: a single-center, single-arm, phase II study
ConclusionSecond-line PD-1 inhibitor combined with albumin paclitaxel and apatinib showed certain efficacy and safety in patients with mGC.Trial registrationClinical trials, NCT04182724. Registered 27 November 2019; retrospectively registered,https://clinicaltrials.gov/study/NCT04182724 (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 12, 2024 Category: Drugs & Pharmacology Source Type: research
CXCR2 antagonist navarixin in combination with pembrolizumab in select advanced solid tumors: a phase 2 randomized trial
SummaryC-X-C motif chemokine receptor 2 (CXCR2) has a role in tumor progression, lineage plasticity, and reduction of immune checkpoint inhibitor efficacy. Preclinical evidence suggests potential benefit of CXCR2 inhibition in multiple solid tumors. In this phase 2 study (NCT03473925), adults with previously treated advanced or metastatic castration-resistant prostate cancer (CRPC), microsatellite-stable colorectal cancer (MSS CRC), or non –small-cell lung cancer (NSCLC) were randomized 1:1 to the CXCR2 antagonist navarixin 30 or 100 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks up to 35 cycl...
Source: Investigational New Drugs - February 7, 2024 Category: Drugs & Pharmacology Source Type: research
Phase 1 study of pembrolizumab plus chemotherapy in Japanese patients with extensive-stage small-cell lung cancer
ConclusionPembrolizumab in combination with platinum-etoposide therapy had manageable toxicity with no new safety signals and was associated with antitumor activity in Japanese patients with ES-SCLC.Trial RegistrationClinicalTrials.gov, NCT01840579. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 1, 2024 Category: Drugs & Pharmacology Source Type: research
Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort
SummaryNavitoclax (ABT-263) is an oral BCL2 homology-3 mimetic that binds with high affinity to pro-survival BCL2 proteins, resulting in apoptosis. Sorafenib, an oral multi kinase inhibitor also promotes apoptosis and inhibits tumor angiogenesis. The efficacy of either agent alone is limited; however, preclinical studies demonstrate synergy with the combination of navitoclax and sorafenib. In this phase 1 study, we evaluated the combination of navitoclax and sorafenib in a dose escalation cohort of patients with refractory solid tumors, with an expansion cohort in hepatocellular carcinoma (HCC). Maximum tolerated dose (MTD...
Source: Investigational New Drugs - January 25, 2024 Category: Drugs & Pharmacology Source Type: research
Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis
Summary Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (4...
Source: Investigational New Drugs - January 23, 2024 Category: Drugs & Pharmacology Source Type: research
Fibroids and unexplained infertility treatment with epigallocatechin gallate: a natural compound in green tea (FRIEND) - protocol for a randomised placebo-controlled US multicentre clinical trial of EGCG to improve fertility in women with uterine fibroids
This study addresses the pressing need for non-hormonal, non-surgical treatment options for women with fibroids desiring pregnancy. Previous preclinical and clinical studies have shown that epigallocatechin gallate (EGCG) effectively reduces uterine fibroid size. We hypothesise that EGCG from green tea extract will shrink fibroids, enhance endometrial quality and increase pregnancy likelihood. To investigate this hypothesis, we initiated a National Institute of Child Health and Human Development Confirm-funded trial to assess EGCG’s efficacy in treating women with fibroids and unexplained infertility.
Methods and an...
Source: BMJ Open - January 12, 2024 Category: General Medicine Authors: Al-Hendy, A., Segars, J. H., Taylor, H. S., Gonzalez, F., Siblini, H., Zamah, M., Alkelani, H., Singh, B., Flores, V. A., Christman, G. M., Johnson, J. J., Huang, H., Zhang, H. Tags: Open access, Obstetrics & Gynaecology Obstetrics and gynaecology Source Type: research
A bispecific antibody targeting HER2 and CLDN18.2 eliminates gastric cancer cells expressing dual antigens by enhancing the immune effector function
AbstractGastric cancer (GC) is widely regarded as one of the toughest cancers to treat. Trastuzumab, which targets the human epidermal growth factor receptor 2 (HER2) for GC treatment, has demonstrated clinical success. However, these patients have a high likelihood of developing resistance. Additionally, Claudin18.2 (CLDN18.2) is a promising emerging target for GC treatment. Therefore, therapies that simultaneously target both HER2 and CLDN18.2 targets are of great significance. Here, we constructed a bispecific antibody targeting both HER2 and CLDN18.2 (HC-2G4S; BsAb), which displayed satisfactory purity, thermostability...
Source: Investigational New Drugs - January 10, 2024 Category: Drugs & Pharmacology Source Type: research
Human Hepatic Spheroid Coculture Model for the Assessment of Drug-Induced Liver Injury
Methods Mol Biol. 2024;2749:85-90. doi: 10.1007/978-1-0716-3609-1_8.ABSTRACTAccurate evaluation of potential drug risks such as drug-induced liver injury (DILI) continues to be a challenge faced by pharmaceutical industry and regulatory agencies. Preclinical testing has served as a foundation for the evaluation of the potential risks and effectiveness of investigational new drug (IND) products in humans. However, current two-dimensional (2D) in vitro human primary hepatocyte (HPH) culture systems cannot accurately depict and simulate the rich environment and complex processes observed in vivo, while animal studies present ...
Source: Mol Biol Cell - December 22, 2023 Category: Molecular Biology Authors: Linhao Li Hongbing Wang Source Type: research
Human Hepatic Spheroid Coculture Model for the Assessment of Drug-Induced Liver Injury
Methods Mol Biol. 2024;2749:85-90. doi: 10.1007/978-1-0716-3609-1_8.ABSTRACTAccurate evaluation of potential drug risks such as drug-induced liver injury (DILI) continues to be a challenge faced by pharmaceutical industry and regulatory agencies. Preclinical testing has served as a foundation for the evaluation of the potential risks and effectiveness of investigational new drug (IND) products in humans. However, current two-dimensional (2D) in vitro human primary hepatocyte (HPH) culture systems cannot accurately depict and simulate the rich environment and complex processes observed in vivo, while animal studies present ...
Source: Mol Biol Cell - December 22, 2023 Category: Molecular Biology Authors: Linhao Li Hongbing Wang Source Type: research
Targeted delivery of liposomal Ribociclib to SLC7A5 transporters in breast cancer cells
This study aimed to prepare SLC7A5 transporters targeted liposomes of Ribociclib (RB) by stear(o)yl conjugation of Phe, Asp, Glu amino acids to liposomes as targeting moieties. The liposomes were optimized for their formulations. Cell analysis on two cell lines of MCF-7 and NIH-3T3 were done including; cell viability test by MTT assay, cellular uptake, and cell cycle arrest by flow cytometry. The optimal liposomes showed the particle size of 123.6 ± 1.3 nm, drug loading efficiency and release efficiency of 83.87% ± 1.33% and 60.55% ± 0.46%, respectively. The RB loaded liposomes showed no hemolysis activity....
Source: Investigational New Drugs - December 21, 2023 Category: Drugs & Pharmacology Source Type: research
Benefit assessment of extended dosing in cancer patients after their withdrawal from clinical trials
Conclusion: Extended dosing can indeed provide benefits, including survival benefits and economic benefits, to cancer patients after their withdrawal from clinical trials and will clinically present an additional treatment option for patients. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - December 15, 2023 Category: Drugs & Pharmacology Source Type: research
Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects
ConclusionThe overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased Cmax in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 15, 2023 Category: Drugs & Pharmacology Source Type: research
The potential value of 5-androstenediol in countering acute radiation syndrome
Drug Discov Today. 2023 Dec 12:103856. doi: 10.1016/j.drudis.2023.103856. Online ahead of print.ABSTRACTModerate-to-high doses of ionizing irradiation can lead to potentially life-threatening morbidities and increase mortality risk. In preclinical testing, 5-androstenediol has been shown to be effective in protecting against hematopoietic acute radiation syndrome. This agent is important for innate immunity, serves to modulate cell cycle progression, reduces radiation-induced apoptosis, and regulates DNA repair. The drug has been evaluated clinically for its pharmacokinetics and safety. The United States Food and Drug Admi...
Source: Drug Discovery Today - December 14, 2023 Category: Drugs & Pharmacology Authors: Vijay K Singh Thomas M Seed Source Type: research
The potential value of 5-androstenediol in countering acute radiation syndrome
Drug Discov Today. 2023 Dec 12:103856. doi: 10.1016/j.drudis.2023.103856. Online ahead of print.ABSTRACTModerate-to-high doses of ionizing irradiation can lead to potentially life-threatening morbidities and increase mortality risk. In preclinical testing, 5-androstenediol has been shown to be effective in protecting against hematopoietic acute radiation syndrome. This agent is important for innate immunity, serves to modulate cell cycle progression, reduces radiation-induced apoptosis, and regulates DNA repair. The drug has been evaluated clinically for its pharmacokinetics and safety. The United States Food and Drug Admi...
Source: Drug Discovery Today - December 14, 2023 Category: Drugs & Pharmacology Authors: Vijay K Singh Thomas M Seed Source Type: research
