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
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
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
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
Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage
SummaryIn recent years, a number of novel pharmaceutical agents have received approval for the management of acute myeloid leukemia (AML). However, there is still ample opportunity for enhancing efficacy. The Wee1 inhibitor adavosertib (ADA) shows promise for the treatment of AML. Based on the effect of drugs on DNA damage, we conducted a combination study involving ADA and fimepinostat (CUDC-907), a dual inhibitor of PI3K and histone deacetylase (HDAC). We observed that the combination of CUDC-907 and ADA exhibited a synergistic effect in enhancing the antileukemic activity in both AML cell lines and primary patient sampl...
Source: Investigational New Drugs - December 12, 2023 Category: Drugs & Pharmacology Source Type: research
RPTOR mutation: a novel predictor of efficacious immunotherapy in melanoma
SummaryIdentifying biomarkers to evaluate the therapeutic effect of immune checkpoint inhibitors (ICIs) is crucial. Regulatory Associated Protein of MTOR Complex 1 (RPTOR), one of the genes in the mTOR pathway, plays a role in regulating tumor progression. However, the connection between RPTOR mutation and the efficacy of ICIs in melanoma remains unclear. The data of ICIs-treated melanoma patients in discovery (n = 384) and validation (n = 320) cohorts were obtained from cBioPortal databases. The genomic data in the two cohorts was used to investigate the connection between RPTOR mutation and immunotherapy efficac...
Source: Investigational New Drugs - December 10, 2023 Category: Drugs & Pharmacology Source Type: research
Clinical characteristics, diagnosis, treatment, and prognosis of nivolumab induced gastritis
SummaryGastritis has recently been reported to be associated with nivolumab, and the clinical characteristics of nivolumab induced gastritis remain unclear. To explore the clinical characteristics of nivolumab induced gastritis, and to provide reference for the classification and treatment guidelines of immune checkpoint inhibitors -related gastritis. Case reports, case series, and clinical studies of nivolumab induced gastritis were retrospectively analyzed by searching the database from the establishment of the database until September 30, 2023. Forty-seven were included, with a median age of 57 years (range 16, 93). T...
Source: Investigational New Drugs - December 8, 2023 Category: Drugs & Pharmacology Source Type: research
A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I-
SummaryDexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemothera...
Source: Investigational New Drugs - December 6, 2023 Category: Drugs & Pharmacology Source Type: research
Phase I/II trial of BMS-986,205 and nivolumab as first line therapy in hepatocellular carcinoma
ConclusionCombination BMS-986,205 and nivolumab showed a manageable safety profile with durable benefit as first-line therapy in a meaningful subset of advanced HCC patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 1, 2023 Category: Drugs & Pharmacology Source Type: research
Molecular profiling and prognostic analysis in Chinese cholangiocarcinoma: an observational, retrospective single-center study
This study provides an overview of genetic alterations in Chinese patients with CCA, which will provide novel potential biomarkers for the diagnosis of CCA and may guide targeted therapeutic strategies for Chinese patients with CCA. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 17, 2023 Category: Drugs & Pharmacology Source Type: research
Immunoneoadjuvant therapy with immune checkpoint inhibitors of gastric cancer: an emerging exemplification
This article reviews the progress in the use of ICI monotherapy and in combination with alternative therapies for the treatment of gastric cancer to aid in the development of gastric cancer immunoneoadjuvant therapy and improve the overall therapeutic benefit. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 16, 2023 Category: Drugs & Pharmacology Source Type: research
Endosomal recycling inhibitors downregulate the androgen receptor and synergise with enzalutamide
SummaryProstate cancer is the second most frequent cancer diagnosed in men, and accounts for one-fifth of cancer associated deaths worldwide. Despite the availability of effective prostate cancer therapies, if it is not cured by radical local treatment, progression to drug resistant metastatic prostate cancer is inevitable. Therefore, new drugs and treatment regimens are urgently required to overcome resistance. We have recently published research demonstrating that targeting the endosomal recycling pathway, a membrane transport pathway that recycles internalised cell surface proteins back to the plasma membrane, may be a ...
Source: Investigational New Drugs - November 14, 2023 Category: Drugs & Pharmacology Source Type: research
The ATR inhibitor berzosertib acts as a radio- and chemosensitizer in head and neck squamous cell carcinoma cell lines
AbstractAlterations in the DNA damage response play a crucial role in radio- and chemoresistance of neoplastic cells. Activation of the Ataxia telangiectasia and Rad3-related (ATR) pathway is an important DNA damage response mechanism in head and neck squamous cell carcinoma (HNSCC). Berzosertib, a selective ATR inhibitor, shows promising radio- and chemosensitizing effects in preclinical studies and is well tolerated in clinical studies. The aim of this study was to elucidate the effect of berzosertib treatment in combination with radiation and cisplatin in HNSCC. The HNSCC cell lines Cal-27 and FaDu were treated with ber...
Source: Investigational New Drugs - November 7, 2023 Category: Drugs & Pharmacology Source Type: research
