Sitravatinib is a potential EGFR inhibitor and induce a new death phenotype in Glioblastoma
SummaryGlioblastoma (GBM) is a highly lethal neurological tumor that presents significant challenge for clinicians due to its heterogeneity and high mortality rate. Despite extensive research, there is currently no effective drug treatment available for GBM. Research evidence has consistently demonstrated that the epidermal growth factor receptor (EGFR) promotes tumor progression and is associated with poor prognosis in several types of cancer. In glioma, EGFR abnormal amplification is reported in approximately 40% of GBM patients, with overexpression observed in 60% of cases, and deletion or mutation in 24% to 67% of pati...
Source: Investigational New Drugs - June 16, 2023 Category: Drugs & Pharmacology Source Type: research
POTEE mutation as a potential predictive biomarker for immune checkpoint inhibitors in lung adenocarcinoma
SummaryPrecise selection of patients who could benefit from immune checkpoint inhibitors (ICIs) is an important challenge for immunotherapy in lung cancer.POTEE (POTE Ankyrin Domain Family Member E) is a member of one primate-specific gene family which have been identified as cancer-related antigens and potential target for immunotherapy of cancer. Here, we investigated the correlation betweenPOTEE mutation and the clinical outcome of ICIs treatment in non-small cell lung cancer (NSCLC). We merged three NSCLC cohorts (n = 165) to assess predictive value ofPOTEE mutation of immunotherapy efficacy in NSCLC. The prognostic an...
Source: Investigational New Drugs - June 15, 2023 Category: Drugs & Pharmacology Source Type: research
A phase I/II study of LY3022855 with BRAF/MEK inhibition in patients with Melanoma
AbstractBRAF/MEK targeted therapies and immune checkpoint inhibition have dramatically improved disease control and survival of patients with advanced melanoma. However, most patients do not have durable benefit from either of these therapies. BRAF targeted therapy often has a limited duration of efficacy due to the development of resistance. Pre-clinical data suggest that one possible way to overcome resistance to BRAF/MEK targeted therapy may be the addition of CSF1R inhibition. In this phase I/II study we evaluated the safety and efficacy of LY3022855, an anti-colony stimulating factor-1 receptor (CSF-1R) monoclonal ant...
Source: Investigational New Drugs - May 29, 2023 Category: Drugs & Pharmacology Source Type: research
Correction to: The kinesin motor protein KIF4A as a potential therapeutic target in renal cell carcinoma
(Source: Investigational New Drugs)
Source: Investigational New Drugs - May 27, 2023 Category: Drugs & Pharmacology Source Type: research
Degradation of MYC by the mutant p53 reactivator drug, COTI-2 in breast cancer cells
AbstractTP53 (p53) and MYC are amongst the most frequently altered genes in cancer. Both are thus attractive targets for new anticancer therapies. Historically, however, both genes have proved challenging to target and currently there is no approved therapy against either. The aim of this study was to investigate the effect of the mutant p53 reactivating drug, COTI-2 on MYC. Total MYC, pSer62 MYC and pThr58 MYC were detected using Western blotting. Proteasome-mediated degradation was determined using the proteasome, inhibitor MG-132, while MYC half-life was measured using pulse chase experiments in the presence of cyclohex...
Source: Investigational New Drugs - May 26, 2023 Category: Drugs & Pharmacology Source Type: research
Bispecific anti-CD3 ×anti-CD155 antibody mediates T-cell immunotherapy in human haematologic malignancies
In conclusion, CD155Bi-Ab enhances the ability of T cells to kill haematologic tumour cells, and therefore, CD155 may serve as a novel target for immunotherapy against haematologic malignancies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 17, 2023 Category: Drugs & Pharmacology Source Type: research
A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors
This study investigated dosing schedules for adavosertib monotherapy, determining the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) in patients with advanced solid tumors.Patients received oral adavosertib qd or bid on a 5/9 schedule (5 days on treatment, 9 days off) in 14-day cycles, or qd on one of two 5/2 schedules (weekly, or for 2 of 3 weeks) in 21-day cycles. Safety, efficacy, and pharmacokinetic analyses were performed.Sixty-two patients (female, 64.5%; median age, 61.5 years; most common primary tumors: lung [24.2%], ovary [21.0%]) received treatment (qd schedules, n  = 50; bid schedules, nâ...
Source: Investigational New Drugs - May 12, 2023 Category: Drugs & Pharmacology Source Type: research
Abdominal pain accompanied by elevated serum inflammatory markers and biliary enzymes for diagnosing immune checkpoint inhibitor-induced sclerosing cholangitis
In this study, we aimed to summarize the clinical features of irSC. Clinical data were collected retrospectively from 1,393 patients with advanced malignancy treated with immune-checkpoint inhibitors (ICIs) between August 2014 and October 2021. We analyzed patients with immune-related adverse events of liver injury (liver-irAEs) and compared irSC and non-irSC groups. Sixty-seven patients (4.8%) had a liver-irAE ( ≥ grade 3) during the follow-up period (median, 262 days). Among these, irSC was observed in eight patients (11.9%). All patients in the irSC group were treated with anti-PD-1/PD-L1 antibodies. Compared with the...
Source: Investigational New Drugs - May 12, 2023 Category: Drugs & Pharmacology Source Type: research
Pharmacokinetics, safety, and antitumor activity of talazoparib monotherapy in Chinese patients with advanced solid tumors
AbstractTalazoparib, a poly(ADP-ribose) polymerase inhibitor, has demonstrated efficacy in the treatment of advanced breast and prostate cancers in Western populations. This open-label, phase 1 study investigated the pharmacokinetics, safety, and antitumor activity of talazoparib monotherapy in Chinese patients with advanced solid tumors. Molecularly unselected patients ( ≥18 years) with advanced solid tumors resistant to standard therapy received talazoparib (oral, 1 mg once daily). Primary endpoint was characterization of single-dose and steady-state pharmacokinetics. Secondary endpoints evaluated safety, unconfirmed o...
Source: Investigational New Drugs - May 12, 2023 Category: Drugs & Pharmacology Source Type: research
Correction to: A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies
(Source: Investigational New Drugs)
Source: Investigational New Drugs - May 11, 2023 Category: Drugs & Pharmacology Source Type: research
Comparison of safety outcomes of anticancer drugs in Japanese and non-Japanese patients in multi-regional clinical trials: meta-analysis of safety profiles
This study aimed to compare the safety outcomes of anticancer drugs in Japanese and non-Japanese patients in multi-regional clinical trials (MRCTs), regardless of the type of cancer or drug. All new approvals of oncology drugs in Japan from January 2009 to December 2018 were searched through the Pharmaceuticals and Medical Devices Agency website. The odds ratio (OR) for comparing the incidence of AEs between Japanese and non-Japanese patients was estimated using the Mantel –Haenszel method with a random effect model. Sixty-six multi-regional phase 3 trials were identified involving 43,712 patients. Severe AE, AE leading ...
Source: Investigational New Drugs - May 10, 2023 Category: Drugs & Pharmacology Source Type: research
Epigenetic modifiers either individually or in specific combinations impair viability of patient-derived glioblastoma cell line while exhibit moderate effect on normal stem cells growth
In this study, we extended our investigation to include a patient-derived GBM stem cell line. Our results showed that the combinations of modulators of histone and DNA covalent modifying enzymes that synergistically suppress D54 and U87 cell line growth also impair the viability of the patient-derived GBM stem cell line. These findings suggest that epigenetic modifiers alone or in specific combinations exhibit a cytotoxic effect on established and low-passage patient-derived GBM cell lines, and thus could be a promising therapeutic approach for this type of brain cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 10, 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
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 Â 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
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
