Multi-Omics and Single-Cell Insights Reveal a Lysophosphatidic Acid (LPA)-Mediated Resistant Mechanism to Third Generation EGFR-TKI in Non-Small Cell Lung Cancer.

Introduction: Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of EGFR-sensitive-mutant non-small cell lung cancer (NSCLC). However, acquired resistance remains a significant challenge. This study investigates the metabolic mechanisms driving third-generation EGFR-TKI resistance.

Efficacy and Safety of Afatinib Plus Bevacizumab as First-Line Treatment for Advanced NSCLC Patients With Epidermal Growth Factor Receptor (EGFR) Mutations: A Multicenter, Phase II Trial.

Background: Studies indicated that afatinib combined with angiogenesis inhibitor may achieve promising efficacy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations.

Methods: This is a multicenter, Phase II trial to explore the efficacy and safety of afatinib plus bevacizumab at first-line setting for EGFR-mutant NSCLC patients. The primary end point was progression-free survival (PFS).

Efficacy and safety of bevacizumab biosimilar SIBP04 compared with bevacizumab (Avastin®) as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer: A randomized, double-blind, phase 3 trial.

Background: SIBP04 is a biosimilar of bevacizumab (Avastin®, Roche, Basel, Switzerland). This study evaluated the equivalence of SIBP04 to Avastin® as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer (nsqNSCLC).

Methods: In this randomized, double-blind, multi-center, phase 3 trial, we recruited patients with locally advanced or metastatic nsqNSCLC from 58 hospitals at China.

Efficacy and safety of limertinib versus gefitinib as first-line treatment for locally advanced or metastatic non-small-cell lung cancer with EGFR-sensitising mutation: a randomised, double-blind, double-dummy, phase 3 trial.

Background: Limertinib is a new third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This study aimed to prospectively assess the efficacy and safety of limertinib versus gefitinib as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR-sensitising mutation.

Methods: This multicentre, randomised, double-blind, double-dummy, phase 3 trial was done at 56 hospitals in China.

Unraveling the role of HDAC3 as an immunotherapy prognostic biomarker and therapeutic target in advanced non-small cell lung cancer.

Background: This study investigates HDAC3 as a potential immunotherapy biomarker in advanced non-small cell lung cancer (aNSCLC), focusing on its association with treatment response to immune checkpoint inhibitors (ICIs).

Methods: We employed a multi-phase approach in 78 aNSCLC patients with 138 plasma samples, starting with a discovery phase that identified differential autoantibodies (AAbs) using proteomic analysis in responders and non-responders. In the validation phase, we assessed AAb levels at multiple time points.

Multi-omics unveils BCAA metabolism markers L-leucine and HMGCS1 as prognostic marker for immunotherapy efficacy in non-small cell lung cancer.

Background: This study aims to identify branched-chain amino acid (BCAA) plasma metabolites and gene signatures that enhance prognostic assessments in non-small cell lung cancer (NSCLC) patients receiving immunotherapy.

Methods: Plasma metabolites were measured using untargeted UPLC-MS/MS (n = 94 and 40), with lymphocyte subset tests on 72 patients. BCAA-related subtypes were identified in NSCLC datasets (n = 274, 176, and 196).

Safety, pharmacokinetics, and efficacy of abexinostat, an novel histone deacetylase inhibitor, in Chinese patients with relapsed/refractory B cell non-Hodgkin lymphoma: a Phase 1 study.

Objective: Abexinostat, an novel pan-histone deacetylase inhibitor, induces tumor apoptosis and demonstrates therapeutic potential in B cell non-Hodgkin lymphoma (NHL). This phase 1 study investigate the safety, pharmacokinetics (PK), and efficacy of abexinostat in Chinese patients with relapsed/refractory (r/r) B cell NHL.

Methods: Patients with r/r B cell NHL received abexinostat orally at escalating doses of 40 mg twice daily (bis in die, BID), 60 mg BID, and 80 mg BID with a 4-h interval, for seven days followed by a 7-day drug-free interval.

Clinical, immune cell, and genetic features predicting survival and long-term response to first-line chemo-immunotherapy treatment for non-small cell lung cancer.

Introduction: Chemo-immunotherapy has become a standard of care for the first-line treatment of non-small cell lung cancer (NSCLC), but currently still lacks reliable markers to predict therapeutic efficacy and long-term response (LTR).

Methods: In this study, we retrospectively summarized the survival outcome of 319 patients with locally advanced or metastatic NSCLC who received anti-programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) based therapy from January 1st, 2018 to February 28th, 2022 at the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. Then a comprehensive analysis of the association of LTR or survival outcomes with various characteristics including clinical parameters, peripheral blood lymphocyte subsets and common gene mutations in 167 NSCLC patients who received first-line anti-PD-1 plus chemotherapy treatment was conducted.

Single-cell sequencing and spatial transcriptomics reveal FAS+ T cell and autophagy-related signatures predicting chemoimmunotherapy response in diffuse large B-cell lymphoma patients.

Current subtyping methods of diffuse large B-cell lymphoma (DLBCL) could not satisfy the clinical demands for risk assessment and prognostic prediction. We aimed to investigate the prognostic effect of autophagy-related genes (ARGs) in DLBCL. Transcriptomic data of 1,409 DLBCL patients, 531 healthy controls (HCs), and single-cell sequencing data of 4 DLBCL were included.

First-line treatment of anti-EGFR monoclonal antibody cetuximab β plus FOLFIRI versus FOLFIRI alone in Chinese patients with RAS/BRAF wild-type metastatic colorectal cancer: a randomized, phase 3 trial.

Cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. Despite this established approach, cetuximab β (CMAB009), as a modified antibody of cetuximab, prospectively selected for dual RAS/BRAF wild-type patients, has not yet been validated in the Chinese mCRC patients through phase 3 trial. In this study (ClinicalTrials.

Pretreatment plasma sCD14 as a prognostic indicator in advanced non-small cell lung cancer patients undergoing immunotherapy.

Background: This study aims to evaluate cytokines as a prognostic biomarker in patients with advanced non-small cell lung cancer (aNSCLC) undergoing immunotherapy.

Methods: A comprehensive analysis was conducted to assess the prognostic significance of sCD14 and other cytokines in aNSCLC patients receiving immune checkpoint inhibitors (ICIs) using flow fluorescence. A discovery cohort (n = 42) was used to evaluate the differential expression of 41 cytokines between durable clinical benefit (DCB) and no durable benefit (NDB) groups in Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS).

and mutations in peripheral T-cell lymphoma mediating resistance to anti-PD-1 therapy through the STAT3/PD-L1 pathway.

Background: Clinical evidence has established anti-PD-1 antibody as a transformative treatment modality for relapsed/refractory peripheral T-cell lymphoma (r/r PTCL), yet reveals a therapeutic plateau with drug resistance observed in 60% of r/r PTCL. The biological determinants underlying this resistance-particularly the complex interplay between tumor-intrinsic characteristics (including tumor mutation burden and oncogenic mutations) and immune microenvironment features (notably PD-L1 expression)-remain insufficiently illustrated. Therefore, we systematically depicted the comprehensive mutation profile of r/r PTCL patients and correlated them with the efficacy and prognosis of anti-PD-1 therapy.

Telpegfilgrastim for chemotherapy-induced neutropenia in patients with non-small cell lung cancer: a multicentre, randomized, phase 3 study.

Background: Chemotherapy-induced neutropenia (CIN) is usually managed by recombinant human granulocyte colony stimulating factor (rhG-CSF) and pegylated rhG-CSF (PEG-rhG-CSF). This study evaluated the efficacy and safety of telpegfilgrastim, a novel Y-shaped PEG-rhG-CSF, for CIN prophylaxis in patients with non-small cell lung cancer (NSCLC).

Methods: This was a multicentre, randomized, open-label, active-controlled non-inferiority study.

Spatial transcriptomics reveals prognostically LYZ fibroblasts and colocalization with FN1 macrophages in diffuse large B-cell lymphoma.

Background: Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy with diverse patient outcomes, largely influenced by the tumor microenvironment (TME). Understanding the roles of fibroblasts and macrophages within the TME is essential for developing personalized therapeutic strategies in DLBCL.

Methods: This study is a multi-omics approach, integrating spatial transcriptomics (n = 11), bulk transcriptomics (n = 2,499), immunohistochemistry (IHC, n = 37), multiplex immunofluorescence (mIF, n = 56), and plasma samples (n = 240) to identify and characterize fibroblast and tumor-associated macrophage subtypes in the TME.

Rezivertinib versus gefitinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (REZOR): a multicentre, double-blind, randomised, phase 3 study.

Background: This study aimed to compare the efficacy and safety of rezivertinib (BPI-7711) and gefitinib as first-line therapies in patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC).

Methods: This multicentre, double-blind, randomised, phase 3 study (REZOR) included eligible patients from 50 hospitals across China. Those who had been histologically or cytologically confirmed as having NSCLC with EGFR exon 19 deletion or exon 21 Leu858Arg mutation by central laboratory were randomly assigned (1:1) to receive once daily either rezivertinib 180 mg or gefitinib 250 mg, until unacceptable toxicity occurred, disease progression, or other treatment discontinuation criteria were met.

Efficacy, safety, and multi-omics analysis of pembrolizumab combined with nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: A single-arm phase 2 study.

Objective: Based on the findings of the KEYNOTE-048 study, pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum in such patients remain unexplored.

Methods: This single-arm phase 2 study enrolled patients with R/M HNSCC who received pembrolizumab (200 mg), nab-paclitaxel (260 mg/m²), and either cisplatin (75 mg/m²) or carboplatin [area under the curve (AUC) 5] every 21 d for up to six cycles, followed by pembrolizumab maintenance therapy.

Glecirasib in KRAS-mutated nonsmall-cell lung cancer: a phase 2b trial.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).

Artificial neural network systems to predict the response to sintilimab in squamous-cell non-small-cell lung cancer based on data of ORIENT-3 study.

Background: Existing biomarkers and models for predicting response to programmed cell death protein 1 monoclonal antibody in advanced squamous-cell non-small cell lung cancer (sqNSCLC) did not have enough accuracy. We used data from the ORIENT-3 study to construct artificial neural network (ANN) systems to predict the response to sintilimab for sqNSCLC.

Methods: Four ANN systems based on bulk RNA data to predict disease control (DC), immune DC (iDC), objective response (OR) and immune OR (iOR) were constructed and tested for patients with sqNSCLC treated with sintilimab.

Proteomic profiling reveals the significance of lipid metabolism in small cell lung cancer recurrence and metastasis.

Background: Small cell lung cancer (SCLC) is a lethal and recalcitrant malignancy with early metastases. However, the molecular and cellular mechanisms underlying its aggressive characteristics remain relatively elusive.

Methods: In this study, we conducted a comprehensive proteomic analysis of 90 primary tumors, 15 patient-matched lymph node metastatic tumors, and 15 brain metastatic tumors derived from a cohort of 105 SCLC patients.

Safety and efficacy of amulirafusp alfa (IMM0306), a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a phase 1/2 study.

Background: Amulirafusp alfa (IMM0306) is a fusion protein of CD47 binding domain of signal-regulatory protein alpha (SIRPα) with CD20 monoclonal antibody on both heavy chains. This study aimed to evaluate the safety and preliminary efficacy of amulirafusp alfa in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL).

Methods: We enrolled patients with CD20 + r/r B-NHL who had previously received at least two lines of therapy to receive a single-dose of amulirafusp alfa in the first 2 weeks, followed by a multiple-dose period, in which the patients received the same intravenous dose every week in 4-week cycles.

Plasma metabolomics profiling of EGFR-mutant NSCLC patients treated with third-generation EGFR-TKI.

Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the latest and a vital treatment option for non-small cell lung cancer (NSCLC) patients. Although EGFR-sensitive mutations are an indication for third-generation EGFR-TKI therapy, 30% of NSCLC patients lack response and all patients inevitably progress. There is a lack of biomarkers to predict the efficacy of EGFR-TKI therapy.

Spatial analyses revealed CXCL5 and SLC6A14 as the markers of microvascular invasion in intrahepatic cholangiocarcinoma.

Background: Microvascular invasion (MVI) is a critical prognostic factor in intrahepatic cholangiocarcinoma (ICC), strongly associated with postoperative recurrence. However, the phenotypic features and spatial organization of MVI remain inadequately understood.

Methods: We performed a spatial transcriptomic analysis on 29,632 spots from six ICC samples, manually delineating MVI clusters using the cloupe software.