Pharmacokinetics, safety, and efficacy of mixed formulation of fosrolapitant and palonosetron (HR20013) in combination with dexamethasone in patients with solid tumors scheduled for highly emetogenic cisplatin-based chemotherapy: a phase I trial.

Background: This phase I trial aimed to assess the pharmacokinetics (PK), safety, and preliminary efficacy of a single dose of HR20013 (mixed formulation of fosrolapitant and palonosetron) plus dexamethasone in patients with malignant solid tumors.

Methods: Solid tumor patients who were naive to cisplatin-based chemotherapy and scheduled to receive the single-day cisplatin-based chemotherapy were enrolled. Patients would receive a single intravenous infusion of HR20013 (Day 1) before cisplatin-based chemotherapy, alongside oral dexamethasone (Day 1, 12 mg, once a day; Day 2-4, 3.

Toripalimab Combination Therapy Without Concurrent Cisplatin for Nasopharyngeal Carcinoma: The DIAMOND Randomized Clinical Trial.

Importance: With the programmed cell death protein 1 (PD-1) blockade toripalimab, omitting highly toxic concurrent cisplatin may be feasible for nasopharyngeal carcinoma (NPC) without compromising survival.

Objective: To evaluate the efficacy and safety of toripalimab incorporated into induction chemotherapy and radiotherapy, without concurrent cisplatin, for locoregionally advanced NPC.

Design, Setting, And Participants: Open-label, multicenter, randomized phase 3 clinical trial conducted from August 2021 to July 2022 at 13 hospitals in China, enrolling 532 patients with T4N1M0 or T1-4N2-3M0 NPC; 400 (75.

Iparomlimab and tuvonralimab (QL1706) plus chemotherapy and bevacizumab for EGFR-mutant patients with advanced non-small cell lung cancer after failure of EGFR-tyrosine kinase inhibitors: updated results from cohort 5 in the DUBHE-L-201 study.

Iparomlimab and tuvonralimab (QL1706), a bifunctional anti-programmed death-1/cytotoxic T-lymphocyte antigen-4 antibody, in combination with bevacizumab and doublet chemotherapy was tolerable and showed preliminary antitumor activity in advanced non-small cell lung cancer (NSCLC) in DUBHE-L-201 study. Here, we report the updated data of long-term survival prognosis and safety from cohort 5. Epidermal growth factor receptor (EGFR)-mutant patients who progressed on EGFR-tyrosine kinase inhibitors (TKIs) were enrolled in cohort 5 and received QL1706 (5 mg/kg) combined with bevacizumab, pemetrexed and carboplatin in a three-week cycle for up to four cycles followed by maintenance therapy of QL1706, bevacizumab and pemetrexed.

Discovery of a potent BRD4 PROTAC and evaluation of its bioactivity in breast cancer cell lines.

Proteolysis targeting chimeras (PROTACs) targeting bromodomain-containing protein 4 (BRD4) proved to be powerful BRD4 degraders, which showed superiority in vitro and in vivo anti-tumor activity in many cancer models. Referring to the design of ARV-825, ARV-771 and MZ1, two novel BRD4 PROTACs were rationally designed and prepared via connecting the pan-BET selective bromodomain inhibitor JQ1 and two universal E3 ligase ligands targeting Von Hippel-Lindau (VHL) and cereblon (CRBN), namely VHL-JQ1 and CRBN-JQ1. Comparable to the degradation potency of ARV-825, ARV-771, and MZ1, both BRD4 PROTACs demonstrated potent BRD4 degradation efficacy.

Phase I Clinical Trial of CVL218, a Novel PARP1/2 Inhibitor, in Patients with Advanced Solid Tumors.

CVL218, a novel poly ADP-ribose polymerase (PARP1/2) inhibitor, has strong PARP1/2 selective inhibitory activity and high oral bioavailability. We aimed to assess the safety and tolerability of CVL218 in patients with pretreated advanced solid tumors. Patients in this phase I dose escalation trial received one dose of CVL218 (50, 100, 200, 350, 500, 600, 700, and 850 mg) twice a day.

Mitochondrial mass and mitochondrial membrane potential of peripheral lymphocytes: promising biomarkers of systemic lupus erythematosus.

Background: Mitochondrial dysfunction is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Single-cell mitochondrial mass (SCMM), low mitochondrial membrane potential (MMP-Low) in lymphocytes, and circulating mitochondrial DNA (mtDNA) can reflect mitochondrial impairment and may serve as potential novel biomarkers for SLE.

Purpose: We investigated the diagnostic utility of MMP-Low and SCMM in lymphocytes, as well as circulating mtDNA levels, in patients with SLE and examined their correlation with disease activity.

Evaluating the tumor response assessment of modified-RECIST 1.1 in advance non-small cell lung cancer: a analysis of 1,147 patients from the EAST-LC trial.

Background: Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) provides conventional response evaluation in solid tumors.

The next generation of immunotherapies for lung cancers.

Immunotherapies, specifically immune-checkpoint inhibitors (ICIs) targeting PD-(L)1 or CTLA4, have revolutionized the treatment of lung cancer; however, many patients do not have a response to ICIs and most of those with an initial tumour response eventually have disease progression owing to acquired resistance. Over the past few years, numerous therapeutic strategies have been explored to address the problems of intrinsic and acquired resistance to ICIs. In 2024, regulatory approvals of the bispecific PD-1 × VEGF antibody ivonescimab for the treatment of non-small-cell lung cancer in China and the bispecific DLL3 × CD3 T cell engager tarlatamab for patients with small cell lung cancer in the USA provided clinical proof-of-concept for overcoming the challenge of ICI resistance using novel immunotherapeutic agents, thereby increasing enthusiasm for the exploration of next-generation immunotherapies for lung cancer.

Anti-OX40 antibody BAT6026 in patients with advanced solid tumors: A multi-center phase I study.

BAT6026 is a fully human IgG1 OX40 monoclonal antibody. This was a multicenter, open-label, dose escalation, and dose expansion phase I study of BAT6026 conducted in patients with advanced solid tumors who failed standard treatment. Patients received BAT6026 injections ranging from 0.

HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non-small cell lung cancer.

Background: The C797S mutation is one of the most common mechanisms of acquired resistance to third generation EGFR TKIs, yet no approved therapies have been available to target it. Here we developed a novel selective EGFR C797S inhibitor, HS-10375, and report the results of pre-clinical research and the first-in-human phase 1 trial.

Methods: Ba/F3 cell lines and patient-derived cells expressing mutant EGFR were used to test the selectively inhibitory potency of HS-10375 in vitro, and cell line-derived xenograft animal models were used to evaluate the anticancer efficacy of HS-10375 in vivo.

Phase 1b/2 study of ADG106, a 4-1BB/CD137 agonist, in combination with toripalimab in patients with advanced solid tumors.

This phase 1b/2 clinical trial (NCT04775680) evaluated the safety, efficacy, pharmacokinetics and pharmacodynamics of ADG106, a ligand-blocking agonistic antibody targeting CD137 (4-1BB), combined with toripalimab in patients with advanced malignancies. ADG106 0.75-3 mg/kg plus toripalimab 240 mg were administered every 3 weeks.

Endoscopic variceal ligation combined with carvedilol versus endoscopic variceal ligation combined with propranolol for the treatment of oesophageal variceal bleeding in cirrhosis: study protocol for a multicentre, randomised controlled trial.

Introduction: Liver cirrhosis and its severe complication, oesophageal variceal bleeding (EVB), pose significant health risks. Standard treatment for EVB combines non-selective beta-blockers (NSBB) with endoscopic variceal ligation (EVL). Carvedilol, an NSBB with additional benefits, is preferred for compensated cirrhosis.

Izalontamab (SI-B001), a novel EGFRxHER3 bispecific antibody in patients with Locally Advanced or Metastatic Epithelial Tumor: Results from first-in-human phase I/Ib study.

Purpose: Izalontamab (SI-B001) is a novel EGFR×HER3 bispecific antibody. This first-in-human phase I study presents the safety and pharmacokinetics of izalontamab.

Patients And Methods: Previously treated patients with locally advanced or metastatic epithelial tumors were enrolled in the dose-escalation or dose-expansion phases.

The transcription factor MYB30 promotes iron homeostasis by maintaining the stability of the FIT transcription factor.

Iron (Fe) is a vital nutrient for the growth and development of plants. In Arabidopsis (Arabidopsis thaliana), the bHLH transcription factor FER-LIKE IRON-DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT) plays a pivotal role in regulating the response to Fe deficiency. Our study reveals that the R2R3-MYB transcription factor MYB30 is a positive regulator of the Fe-deficiency response by regulating FIT stability.

A B7H3-targeting antibody-drug conjugate in advanced solid tumors: a phase 1/1b trial.

Antibody-drug conjugates (ADCs) have emerged as a transformative modality in the treatment of solid tumors. YL201, a novel B7H3-targeting ADC, leverages a tumor microenvironment activable linker-payload platform, coupled with a novel topoisomerase 1 inhibitor via a protease-cleavable linker. Here we report the findings from a large-scale, global, multicenter, phase 1 trial evaluating the safety, pharmacokinetics and preliminary efficacy of YL201 in patients with advanced solid tumors refractory to standard therapies.

Adjuvant PD-1 Blockade With Camrelizumab for Nasopharyngeal Carcinoma: The DIPPER Randomized Clinical Trial.

Importance: Approximately 20% to 30% of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) experience disease relapse despite definitive chemoradiotherapy. The programmed cell death 1 (PD-1) blockade camrelizumab has demonstrated considerable value in recurrent or metastatic NPC, while its role in locoregionally advanced NPC is unclear.

Objective: To evaluate the efficacy and safety of adjuvant camrelizumab for patients with locoregionally advanced NPC.

Nivolumab combined with induction chemotherapy and radiotherapy in nasopharyngeal carcinoma: A multicenter phase 2 PLATINUM trial.

Severe toxicities caused by concurrent cisplatin are a critical problem in nasopharyngeal carcinoma (NPC) treatment. In this phase 2 multicenter PLATINUM trial (NCT03984357), we recruited 152 NPC patients who received 12-cycle nivolumab plus induction chemotherapy and radiotherapy without concurrent cisplatin. After a median follow-up of 43 months, the 3-year failure-free survival (FFS) was 88.

Safety, pharmacokinetics and efficacy of HA121-28 in patients with advanced solid tumors and RET fusion-positive non-small-cell lung cancer: a multicenter, open-label, single-arm phase 1/2 trial.

HA121-28, a promising multikinase inhibitor, mainly targets rearranged during transfection (RET) fusions and selectively targets vascular endothelial growth factor receptor-2, endothelial growth factor receptor, and fibroblast growth factor receptor 1-3. The safety, pharmacokinetics, and efficacy of HA121-28 were assessed in advanced solid tumors (phase 1, ClinicalTrials.gov NCT03994484) and advanced RET fusion-positive non-small-cell lung cancer (RET-TKI naive NSCLC, phase 2, ClinicalTrials.

First-in-human phase 1 study of an orally bioavailable vascular-disrupting agent DX1002 in patients with advanced solid tumors.

DX1002 is an oral vascular-disrupting agent and exhibits promising results in preclinical studies, leading to tumor vasculature destruction and xenografted tumor necrosis in various animal models. In the phase 1 trial, 17 patients with solid tumors receive DX1002 ranging from 50 to 1,100 mg. The maximum tolerated dose and recommended phase 2 dose of DX1002 are determined as 600 mg once daily.

Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial.

Purpose: Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors.

Methods: Patients with advanced tumors refractory to prior standard therapies were enrolled. In phase Ib, patients received LBL-007 200 mg or 400 mg and toripalimab 240 mg intravenously once every 3 weeks.

The P2X7-Mediated Mitochondrial ROS as an Emerging Core Target of Tuftsin Nanoparticles in Severe Acute Pancreatitis Therapy via Regulating Mitophagy.

20% acute pancreatitis (AP) develops into severe AP (SAP), a global health crisis, with an increased mortality rate to 30%-50%. Mitochondrial damage and immune disorders are direct factors, which exacerbate the occurrence and progression of AP. So far, mitochondrial and immunity injury in SAP remains largely elusive, with no established treatment options available.

programmed myeloid cells expressing novel chimeric antigen receptors show potent anti-tumor activity in preclinical solid tumor models.

Introduction: The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment of B cell malignancies has fueled the development of numerous cell therapies. However, these cell therapies are complex and costly, and unlike in hematological malignancies, outcomes with most T cell therapies in solid tumors have been disappointing. Here, we present a novel approach to directly program myeloid cells by administering novel TROP2 CAR mRNA encapsulated in lipid nanoparticles (LNPs).