PEARL: A Multicenter Phase 2 Study of Lorlatinib in Patients with ALK-Rearranged NSCLC and Central Nervous System Disease.

Background: Patients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) with symptomatic brain (BM) and leptomeningeal (LM) metastases are underrepresented in clinical trials due to poor performance status. Additionally, the need for improved and validated assessment criteria for evaluating central nervous system (CNS) response remains critical. Lorlatinib has demonstrated systemic activity in patients with ALK+ NSCLC.

Alectinib Versus Crizotinib in Asian Patients With Treatment-Naïve Advanced -Positive NSCLC: Five-Year Update From the Phase 3 ALESIA Study.

Introduction: Previous results from the phase 3 ALESIA study (NCT02838420) revealed that alectinib (a central nervous system [CNS]-active, ALK inhibitor) had clinical benefits in treatment-naïve Asian patients with advanced -positive NSCLC, consistent with the global ALEX study. We present updated data after more than or equal to 5 years of follow-up from the "last patient in" date.

Methods: Adult patients with treatment-naïve, advanced -positive NSCLC from mainland China, South Korea, and Thailand were randomized 2:1 to receive twice-daily 600 mg alectinib (n = 125) or 250 mg crizotinib (n = 62).

Tumor immune microenvironment of NSCLC with EGFR exon 20 insertions may predict efficacy of first-line ICI-combined regimen.

Objectives: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified.

Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial.

Background: Patients with EGFR-mutated non-small-cell lung cancer (NSCLC) and MET amplification as a mechanism of resistance to first-line osimertinib have few treatment options. Here, we report the primary analysis of the phase 2 INSIGHT 2 study evaluating tepotinib, a highly selective MET inhibitor, combined with osimertinib in this population.

Methods: This open-label, phase 2 study was conducted at 179 academic centres and community clinics in 17 countries.

Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study.

Purpose: The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations.

Methods: This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with exon 14 skipping (ex14)-mutant NSCLC who had not previously received inhibitors.

Circulating Tumor DNA-Guided De-Escalation Targeted Therapy for Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial.

Importance: Uninterrupted targeted therapy until disease progression or intolerable toxic effects is currently the routine therapy for advanced non-small cell lung cancer (NSCLC) involving driver gene variations. However, drug resistance is inevitable.

Objective: To assess the clinical feasibility of adaptive de-escalation tyrosine kinase inhibitor (TKI) treatment guided by circulating tumor DNA (ctDNA) for achieving complete remission after local consolidative therapy (LCT) in patients with advanced NSCLC.

Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation.

Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC.

Mixed response to the first-line treatment of KRAS G12C inhibitor, sotorasib, in non-small cell lung cancer: A brief report.

Key Clinical Message: One Kirsten Ras () G12C mutated non-small cell lung cancer (NSCLC) patient had improved poor performance status and obtained mixed response with the first-line KRAS-targeted treatment of sotorasib. After disease progression, partial response was achieved with chemotherapy plus immunotherapy. G12C mutated immunoenvironment in NSCLC may favor the immunotherapy.

Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION.

Background: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

Background: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown.

Methods: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy.

Molecular features and clinical outcomes of EGFR-mutated, MET-amplified non-small-cell lung cancer after resistance to dual-targeted therapy.

Background: Some studies of dual-targeted therapy (DTT) targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Consequently, patient management following DTT resistance has gained significance. However, the underlying resistance mechanisms and clinical outcomes in these patients remain unclear.

Plasma ddPCR for the detection of amplification in advanced NSCLC patients: a comparative real-world study.

Background: Mesenchymal-epithelial transition () amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence hybridization (FISH) is the gold standard for amplification detection. However, it is inapplicable when tissue samples are unavailable.

PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial.

No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%).

Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC (CTONG1804): a multicenter open-label phase II study.

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive (N) and nivolumab-chemotherapy (N/C) combinations based on PD-L1 expression. Eligible patients exhibited resectable clinical stage IIA-IIIB (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Patients received either mono-nivolumab (N) or nivolumab + nab-paclitaxel+ carboplatin (N/C) for three cycles based on PD-L1 expression.

Allelic Context of EGFR C797X-Mutant Lung Cancer Defines Four Subtypes With Heterogeneous Genomic Landscape and Distinct Clinical Outcomes.

Introduction: EGFR C797X (C797S or C797G) mutation is the most frequent on-target mechanism of resistance to osimertinib. The hypothesis that the allelic context of C797X/T790M has implications for treatment is on the basis of sporadic reports and needs validation with larger cohorts.

Methods: We identified patients with EGFR C797X-mutant NSCLC from nine centers who progressed on osimertinib, all analyzed in a single laboratory through next-generation sequencing.

Expression of -mutant proteins and genomic evolution in -mutant transformed small cell lung cancer.

Background: The transformation of epidermal growth factor receptor ()-mutant lung adenocarcinoma (LUAD) into small cell lung cancer (SCLC) accounts for 3-14% of the resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs). At present, there is no relevant research to explore the dynamic expression of -mutant proteins and genomic evolution in -mutant transformed SCLC/neuroendocrine carcinoma (NEC).

Methods: Genetic analysis and protein level analysis by next-generation sequencing (NGS), Whole-exome sequencing (WES) and immunohistochemistry were performed to explore expression of -mutant proteins and genomic evolution in -mutant transformed SCLC.

Efficacy, safety and dose selection of AZD3759 in patients with untreated -mutated non-small-cell lung cancer and central nervous system metastases in China (CTONG1702-Arm 8): a multi-center, single-arm, phase 2 trial.

Background: Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration.

Methods: We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402).