EGFR Inhibition Enhances the Cellular Uptake and Antitumor-Activity of the HER3 Antibody-Drug Conjugate HER3-DXd.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for -mutant non-small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of the ERBB family that functions by dimerizing with other ERBB family members (EGFR and HER2) and is frequently overexpressed in -mutant NSCLC.

Genomic and pathological heterogeneity in clinically diagnosed small cell lung cancer in never/light smokers identifies therapeutically targetable alterations.

Small-cell lung cancer (SCLC) occurs infrequently in never/former light smokers. We sought to study this rare clinical subset through next-generation sequencing (NGS) and by characterizing a representative patient-derived model. We performed targeted NGS, as well as comprehensive pathological evaluation, in 11 never/former light smokers with clinically diagnosed SCLC.

Frequency and imaging features of abdominal immune-related adverse events in metastatic lung cancer patients treated with PD-1 inhibitor.

Purpose: To investigate the frequency and imaging features of radiographically evident abdominal immune-related adverse events (irAEs) in patients with metastatic non-small-cell lung cancer (NSCLC) treated with PD-1 inhibitors.

Methods: This retrospective study included 137 patients with metastatic NSCLC treated with PD-1 inhibitor nivolumab monotherapy (75 women; median age: 65 years), who had a baseline CT and at least one follow-up abdomen CT during therapy. Baseline and all follow-up abdominal CTs performed for monitoring of nivolumab therapy were reviewed to identify the organ-specific abdominal irAEs including colitis/enteritis, hepatitis, biliary toxicity, pancreatitis, nephritis, sarcoid-like reaction, and pancreatic and adrenal atrophy.

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells.

Safety and Efficacy of PD-1 Inhibitors Among HIV-Positive Patients With Non-Small Cell Lung Cancer.

Introduction: Despite widespread administration of programmed death receptor 1 (PD-1) pathway inhibitors among individuals with NSCLC, little is known about the safety and activity of these agents among human immunodeficiency virus (HIV) - infected patients since this population has largely been excluded from immunotherapy clinical trials.

Methods: Here, we describe seven patients with metastatic NSCLC and HIV infection who were treated with PD-1 inhibitors nivolumab (two cases) or pembrolizumab (five cases with three in the first-line setting).

Results: Partial responses to immune checkpoint inhibitors were observed in three of seven cases.

Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer.

The anaplastic lymphoma kinase (ALK) is recognized by the immune system as a tumor antigen, and preclinical evidence suggests that ALK-rearranged NSCLCs can also be successfully targeted immunologically using vaccine-based approaches. In contrast to ALK-rearranged lymphomas, the frequency and clinical significance of spontaneous ALK immune responses in patients with ALK-rearranged NSCLCs are largely unknown. We developed an enzyme-linked immunosorbent assay (ELISA) to measure anti-ALK antibody levels and mapped specific peptide epitope sequences within the ALK cytoplasmic domain in patients with non-small cell lung cancer.

Tumor Response Dynamics of Advanced Non-small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome.

We evaluated tumor burden dynamics in patients with advanced non-small cell lung cancer (NSCLC) treated with commercial PD-1 inhibitors to identify imaging markers associated with improved overall survival (OS). The study included 160 patients with advanced NSCLC treated with commercial nivolumab or pembrolizumab monotherapy as a part of clinical care. Tumor burden dynamics were studied for the association with OS.

Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients.

Background: Tumor response characteristics using immune-related RECIST1.1 (irRECIST1.1) in advanced non-small-cell lung cancer (NSCLC) patients treated with nivolumab monotherapy in the clinical setting have not been previously described with a direct comparison with the assessments according to the conventional RECIST1.