Effects on survival of the adverse event of atezolizumab plus bevacizumab for hepatocellular carcinoma: a multicenter study by the Japan Red Cross Liver Study Group
This study aimed to describe the real-world efficacy and safety of the combination therapy of atezolizumab and bevacizumab (Atezo/Bev) for unresectable hepatocellular carcinoma (HCC). This retrospective analysis of a multicenter registry cohort included 268 patients treated with Atezo/Bev. The incidence of adverse events (AE) and its impact on overall survival (OS) and progression-free survival (PFS) were analyzed. Of the 268 patients, 230 (85.8%) experienced AE. The median OS and PFS in the whole cohort were 462 and 239 days, respectively. The OS and PFS were not different in terms of AE, but they were significantly short...
Source: Investigational New Drugs - March 30, 2023 Category: Drugs & Pharmacology Source Type: research
Clinical characteristics, treatment and outcome of nivolumab-induced myasthenia gravis
Conclusion: MG is a serious and rare adverse reaction to nivolumab. Nivolumab-induced MG should be timely and correctly identified, and immunotherapy should be given. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 29, 2023 Category: Drugs & Pharmacology Source Type: research
RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines
In this study, we interrupted GM-CSF expression in CAR-T cells by inserting the GM-CSF shRNA-expression cassette in the CAR vector. Reduction of GM-CSF in CAR-T cells could decrease the level of several proinflammatory cytokines without hampering the killing capacity. The manufacture of GM-CSF knockdown CAR-T cells does not require complicated transfections, which makes it more practical and feasible for clinical application. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 29, 2023 Category: Drugs & Pharmacology Source Type: research
A phase 1b study of the allosteric extracellular FGFR2 inhibitor alofanib in patients with pretreated advanced gastric cancer
We report safety and preliminary efficacy from the first-in-human phase 1b study of alofanib in heavily pretreated patients with advanced gastric cancer. The standard dose-escalation design 3+3 aimed to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Alofanib was administered daily intravenously 5 days on, 2 days off. There were five dose levels (50-350 mg/m2). All patients received alofanib until disease progression or unacceptable toxicity. 21 patients were enrolled. Patients were predominantly male (71%), 67% had 2 and more metastatic sites, including liver metastases (43%), 19% had ECOG P...
Source: Investigational New Drugs - March 13, 2023 Category: Drugs & Pharmacology Source Type: research
Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines
AbstractSmall molecule Bruton ’s tyrosine kinase (BTK) inhibitors have been developed for the treatment of various haemato-oncological diseases, and ibrutinib was approved as the first BTK inhibitor for anticancer therapy in 2013. Previous reports proved the receptor kinase human epidermal growth factor receptor 2 (HER2) to be a valid off-target kinase of ibrutinib and potentially other irreversible BTK inhibitors, as it possesses a druggable cysteine residue in the active site of the enzyme. These findings suggest ibrutinib as a candidate drug for repositioning in HER2-positive breast cancer (BCa). This subtype of breas...
Source: Investigational New Drugs - March 13, 2023 Category: Drugs & Pharmacology Source Type: research
Effective anticancer agents based-on two Pillar[5]arene derivatives for pancreas cancer cell lines: synthesis, apoptotic effect, caspase pathway
This study aimed to evaluate the possible anticancer effects of two different pillar[5]arene derivatives (5Q-[P5] and10Q-P[5]) on two different pancreatic cancer cell linesin vitro. For this purpose, changes in the expression of major genes that play a role in apoptosis and caspase pathways were investigated. Panc-1 and BxPC-3 cell lines were used in the study and the cytotoxic dose of pillar[5]arenes was determined by the MTT method. Changes in gene expression after pillar[5]arenes treatment were evaluated by real-time polymerase chain reaction (qPCR). Apoptosis was studied by flow cytometry. As a result of analysis, it w...
Source: Investigational New Drugs - March 11, 2023 Category: Drugs & Pharmacology Source Type: research
A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies
AbstractTumor-selective viruses are a novel therapeutic approach for treating cancer. Tumor-Specific Immuno Gene Therapy (T-SIGn) vectors are tumor-selective adenoviral vectors designed to express immunomodulatory transgenes. Prolonged activated partial thromboplastin time (aPTT), associated with the presence of antiphospholipid antibodies (aPL), has been observed in patients with viral infections, and following administration of adenovirus-based medicines. aPL may be detected as lupus anticoagulant (LA), anti-cardiolipin (aCL) and/or anti-beta 2 glycoprotein antibodies (a β2GPI). No subtype alone is definitive for develo...
Source: Investigational New Drugs - March 10, 2023 Category: Drugs & Pharmacology Source Type: research
Evaluation of combination treatment with DS-1205c, an AXL kinase inhibitor, and osimertinib in metastatic or unresectable EGFR-mutant non-small cell lung cancer: results from a multicenter, open-label phase 1 study
The objective of this study was to evaluate the safety and tolerability of DS-1205c, an oral AXL-receptor inhibitor, in combination with osimertinib in metastatic or unresectableEFGR-mutant non-small cell lung cancer (NSCLC) patients who developed disease progression during EGFR tyrosine kinase inhibitor (TKI) treatment. An open-label, non-randomized phase 1 study was conducted in Taiwan, in which 13 patients received DS-1205c monotherapy at a dosage of 200, 400, 800, or 1200 mg twice daily for 7 days, followed by combination treatment with DS-1205c (same doses) plus osimertinib 80 mg once daily in 21-day cycles. Treatment...
Source: Investigational New Drugs - March 9, 2023 Category: Drugs & Pharmacology Source Type: research
A phase I dose-escalation study of SYHA1813, a VEGFR and CSF1R inhibitor, in patients with recurrent High-Grade Gliomas or Advanced Solid Tumors
This study aimed to evaluate the safety, pharmacokinetics (PK), and antitumor activity of escalating doses of SYHA1813 in patients with recurrent high-grade gliomas (HGGs) or advanced solid tumors. This study adopted a combination of accelerated titration and a 3 + 3 design for dose escalation, with a starting dose of 5 mg once daily. The dose escalation continued at successive dose levels until the maximum tolerated dose (MTD) was determined. A total of 14 patients were enrolled and treated, including 13 with WHO grade III or IV gliomas and 1 with col orectal cancer. Two patients experienced dose-limiting toxicities...
Source: Investigational New Drugs - March 8, 2023 Category: Drugs & Pharmacology Source Type: research
Phase 1 study to determine the safety and dosing of autologous PBMCs modified to present HPV16 antigens (SQZ-PBMC-HPV) in HLA-A*02+ patients with HPV16+ solid tumors
SummaryWe conducted a dose escalation Phase 1 study of autologous PBMCs loaded by microfluidic squeezing (Cell Squeeze® technology) with HPV16 E6 and E7 antigens (SQZ-PBMC-HPV), in HLA-A*02+ patients with advanced/metastatic HPV16+ cancers. Preclinical studies in murine models had shown such cells resulted in stimulation and proliferation of antigen specific CD8+ cells, and demonstrated antitumor activity. Administration of SQZ-PBMC-HPV was every 3 weeks. Enrollment followed a modified 3+3 design with primary objectives to define safety, tolerability, and the recommended Phase 2 dose. Secondary and exploratory objectives ...
Source: Investigational New Drugs - March 3, 2023 Category: Drugs & Pharmacology Source Type: research
In vitro effects of gamma-secretase inhibition in HPV-positive and HPV-negative head and neck squamous cell carcinoma
ConclusionWe provided novel insights into the potential therapeutic relevance of gamma-secretase inhibition in HNSCC cell lines in vitro. Therefore, PF may become a viable treatment option for patients with HNSCC, particularly for patients with HPV-induced malignancy. Indeed, further in vitro and in vivo experiments should be conducted to validate our results and decipher the mechanism behind the observed anti-neoplastic effects. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 21, 2023 Category: Drugs & Pharmacology Source Type: research
Effect of a moderate CYP3A inducer efavirenz on the pharmacokinetics of fuzuloparib: An open-label, fixed sequence study in Chinese healthy male subjects
SummaryTo evaluate the potential drug-drug interaction (DDI), safety and tolerability of fuzuloparib co-administered with a moderate CYP3A inducer efavirenz in healthy male subjects. Eighteen healthy male subjects were enrolled in a single-center, single-arm, open-label, fixed-sequence study. Fuzuloparib was administered as a single oral 50 mg under a fasting state on day 1, efavirenz (600 mg once daily) was given on days 4–17 before bed time, concomitantly with fuzuloparib on day 18, and for the follow-up 3 additional days (days 19–20). Pharmacokinetic sampling was performed following each fuzuloparib dose. Safety ...
Source: Investigational New Drugs - February 17, 2023 Category: Drugs & Pharmacology Source Type: research
Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study
Conclusion. This study demonstrated a favorable safety and tolerability profile of 48-hour continuous IV infusion of lisavanbulin in patients with solid extracranial tumors or glioblastoma. Clinicaltrials.gov registration: NCT02895360. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 16, 2023 Category: Drugs & Pharmacology Source Type: research
Cyclin-dependent kinase (CDK) 4/6 inhibition in non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations
Conclusion: Combination therapy with CDK4/6 inhibitors and EGFR-TKIs may be a promising approach. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 15, 2023 Category: Drugs & Pharmacology Source Type: research
A phase Ib/II study of BLU-554, a fibroblast growth factor receptor 4 inhibitor in combination with CS1001, an anti-PD-L1, in patients with locally advanced or metastatic hepatocellular carcinoma
Conclusion: Preliminary data showed that BLU-554 in combination with CS1001 is safe and effective for treatment of patients with locally advanced or metastatic HCC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 10, 2023 Category: Drugs & Pharmacology Source Type: research
