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

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

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

Results of an open-label phase 1b study of the ERK inhibitor MK-8353 plus the MEK inhibitor selumetinib in patients with advanced or metastatic solid tumors
Conclusion: MK-8353/selumetinib 50/25 mg and 100/50 mg had acceptable safety and tolerability, whereas 150/75 mg was not tolerable. No responses were observed. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 11, 2023 Category: Drugs & Pharmacology Source Type: research

Iruplinalkib (WX ‑0593), a novel ALK/ROS1 inhibitor, overcomes crizotinib resistance in preclinical models for non-small cell lung cancer
In conclusion, iruplinalkib, a highly active and selective ALK/ROS1 inhibitor, exhibited strong antitumor effects in vitro and in crizotinib-resistant models. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 10, 2023 Category: Drugs & Pharmacology Source Type: research

Immunohistochemical analysis of B7-H3 expression in patients with lung cancer following various anti-cancer treatments
AbstractB7 homolog 3 protein (B7-H3), an immune checkpoint molecule belonging to the B7 family, has been studied as a target for the development of anti-cancer treatment; however, changes in B7-H3 expression during the clinical course remain unknown. This retrospective study aimed to investigate changes in B7-H3 expression of lung cancer specimens in patients with advanced lung cancer following various anti-cancer treatments. The immunohistochemistry (IHC) score was evaluated on a 0 –3 scale, and B7-H3 expression was considered positive for grade ≥ 2. The difference in IHC scores before and after anti-cancer treatm...
Source: Investigational New Drugs - April 10, 2023 Category: Drugs & Pharmacology Source Type: research

SLIT mutations as potential predictive biomarkers for immunotherapy in NSCLC
(Source: Investigational New Drugs)
Source: Investigational New Drugs - April 10, 2023 Category: Drugs & Pharmacology Source Type: research

Mesenchymal stem cells: a trojan horse to treat glioblastoma
SummaryGlioblastoma multiforme (GBM) is the most common and lethal primary tumor of the central nervous system. What makes it so dreadful is the very low survival rate, despite the existence of a standard treatment plan. An innovative and more effective way to treat glioblastoma based on Mesenchymal Stem Cells (MSCs) has been explored recently. MSCs are a group of endogenous multipotent stem cells that could mainly be harvested from adipose tissue, bone marrow, and umbilical cord. Having the ability to migrate toward the tumor using multiple types of binding receptors, they could be used either as a direct treatment (wheth...
Source: Investigational New Drugs - April 5, 2023 Category: Drugs & Pharmacology Source Type: research

Development of a MET-targeted single-chain antibody fragment as an anti-oncogene targeted therapy for breast cancer
AbstractThe usage of monoclonal antibodies (mAbs) and antibody fragments, as a matter associated with the biopharmaceutical industry, is increasingly growing. Harmonious with this concept, we designed an exclusive modeled single-chain variable fragment (scFv) against mesenchymal-epithelial transition (MET) oncoprotein. This scFv was newly developed from Onartuzumab sequence by gene cloning, and expression using bacterial host. Herein, we examined its preclinical efficacy for the reduction of tumor growth, invasiveness and angiogenesis in vitro and in vivo. Expressed anti-MET scFv demonstrated high binding capacity (48.8%) ...
Source: Investigational New Drugs - April 1, 2023 Category: Drugs & Pharmacology Source Type: research

Complete Response to tenalisib and romidepsin with long-term maintenance using tenalisib monotherapy in a patient with relapsed and refractory s ézary syndrome
We report a relapsed/refractory SS patient achieving complete remission using the combination of Tenalisib and Romidepsin and subsequently maintaining long-duration CR with Tenalisib monothera py. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 1, 2023 Category: Drugs & Pharmacology Source Type: research

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