simmitinib (SYHA1817) / CSPC Pharma - LARVOL DELTA

Osimertinib with or without savolitinib as first-line treatment for MET-aberrant, EGFR-mutant NSCLC: randomized phase 2 trial (FLOWERS). (PubMed, Nat Commun) - P2 | "Treatment-related adverse events of grade 3 or higher occurred in 2 patients (8.7%) in cohort 1 and 12 patients (57.1%) in cohort 2. Osimertinib plus savolitinib showed promising antitumor activity and manageable safety."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Osimertinib and stereotactic radiosurgery for brain metastases in EGFR mutated lung cancer - The STARLET joint analysis of OUTRUN and LUOSICNS randomised trials. (PubMed, J Thorac Oncol) - "Adding upfront SRS to osimertinib did not significantly improve 12-month ic-PFS in EGFR mutant NSCLC with BM. This represents the first randomised evidence supporting the use of osimertinib monotherapy as upfront therapy in minimally symptomatic patients with low burden BM."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Savolitinib plus osimertinib versus chemotherapy for advanced, EGFR mutation-positive, MET-amplified non-small-cell lung cancer in China (SACHI): interim analysis of a multicentre, open-label, phase 3 randomised controlled trial. (PubMed, Lancet) - P3 | "The savolitinib-osimertinib combination improved PFS versus chemotherapy in patients with EGFR mutation-positive, MET-amplified NSCLC that had progressed on EGFR TKI therapy, while maintaining a favourable tolerability profile. This regimen offers a potential oral treatment option for this biomarker-selected population."

Journal • P3 data • P3 data: top line • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

A comprehensive clinical trajectory of EGFR A763_Y764insFQEA-positive non-small cell lung cancer treated with fifth-line osimertinib following circulating tumor DNA-based detection: a case report. (PubMed, Transl Lung Cancer Res) - "A 63-year-old Japanese woman with stage IVB lung adenocarcinoma [programmed death ligand-1 (PD-L1) tumor proportion score 70%] received multiple lines of systemic therapy, including pembrolizumab-based chemoimmunotherapy, docetaxel plus ramucirumab, and subsequent cytotoxic regimens. The A763_Y764insFQEA mutation is uniquely sensitive to EGFR-TKIs, and comprehensive molecular testing can guide effective targeted therapy even in later treatment lines. Broader implementation of hybrid-capture-based assays may improve precision oncology outcomes for patients with rare EGFR alterations."

Circulating tumor DNA • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PD-L1

Recurrent Escape from Osimertinib-Induced Senescence Promotes Genomic Instability Associated with Therapeutic Resistance. (PubMed, bioRxiv) - "Despite profound genomic instability, targeting DNA repair or replication stress pathways was ineffective, whereas sensitivity to platinum-based chemotherapy was retained across clades. Collectively, these findings indicate that recurrent senescence escape drives osimertinib resistance through widespread genomic instability and is most effectively treated by cytotoxic strategies rather than pathway-targeted approaches."

Journal • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • TMB

Tumor Exosomal L1 Cell Adhesion Molecule Promotes Brain Metastasis of Lung Cancer. (PubMed, Research (Wash D C)) - "Here, we found that exosomes secreted by lung cancer cells that had acquired epidermal growth factor receptor tyrosine kinase inhibitor resistance and undergone epithelial-mesenchymal transition (osimertinib- and WZ4002-resistant H1975) exhibited enhanced brain-specific distribution and a concomitant increase in BrM compared with exosomes from parental H1975 cells. Clinically, exosomal L1CAM demonstrated diagnostic potential for BrM (area under the curve [AUC] = 0.80), and a combined exosomal L1CAM/ITGB3 panel significantly improved diagnostic accuracy (AUC = 0.98). Collectively, these findings identify exosomal L1CAM as a key regulator of brain-specific metastasis and support the clinical utility of the L1CAM/ITGB3 panel as a noninvasive biomarker for BrM in lung cancer."

Journal • CNS Disorders • Lung Cancer • Oncology • Solid Tumor • CNTN • CNTN2 • EGFR • ITGB3 • L1CAM • NCAM1

Triple-positive non-small cell lung cancer harboring EGFR mutation, ALK rearrangement, and high PD-L1 expression: a case report and literature review. (PubMed, Front Oncol) - "The patient received first-line osimertinib combined with pemetrexed/cisplatin, achieving durable disease control for 17 months...Treatment was switched to alectinib, leading to significant tumor regression and partial response. This case illustrates that in triple-positive NSCLC, initial EGFR-TKI combined with chemotherapy can achieve long-term control, while dynamic molecular profiling at progression is essential for identifying resistance mechanisms. Sequential targeted therapy guided by NGS remains a cornerstone for precision management in this complex molecular subtype."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • EML4 • HER-2 • KIF5B • PD-L1

BiTE (CD3×EGFR)-Based Triplet Therapy Unlocks CD40/CD40L Crosstalk to Revert Immunosuppression in third-generation EGFR-TKI-Refractory NSCLC. (PubMed, J Thorac Oncol) - "This study establishes a novel triple therapy that overcomes the limitations of BiTEs in cold and immunosuppressive TMEs and provides an immunomodulatory approach to addressing third-generation EGFR-TKI resistance."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40LG • CD8 • IFNG

EGFR and IRE1α pathways are associated with distinct immunomodulatory gene expression profiles in NSCLC cells with acquired resistance to EGFR TKIs. (PubMed, Arch Biochem Biophys) - "EGFR-TKI-resistant cell lines were established by long-term exposure to gefitinib, afatinib, and osimertinib via the PC9 model. Targeting endoplasmic reticulum (ER) stress pathways alongside immune checkpoint inhibitors may be crucial for overcoming resistance mechanisms identified here. These insights provide a rationale for personalized treatment strategies tailored to the immune-related gene-expression profiles observed in EGFR-TKI-resistant NSCLC models, aiming to enhance therapeutic responses and improve clinical outcomes."

IO biomarker • Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL2 • CCL22 • CXCL10 • CXCL8 • IFNG • IL6

From Diagnosis, Therapy Decision-Making to Genetic Risk Assessment: The Impact of ctDNA Testing on Comprehensive Cancer Management-A Case Report. (PubMed, J Natl Compr Canc Netw) - "With a primary EGFR p.L858R-mutant NSCLC, osimertinib was administered, resulting in a partial response within 10 months. In addition, given the synchronous primary pancreatic adenocarcinoma, germline testing was performed, revealing a CDKN2A p.I49T variant consistent with melanoma-pancreatic cancer syndrome, prompting comprehensive cancer surveillance and familial testing. This case illustrates how ctDNA testing enabled a comprehensive evaluation by clarifying the diagnosis, identifying actionable biomarkers, and facilitating genetic risk assessment, ultimately having a significant impact on the patient's clinical management."

Biomarker • Circulating tumor DNA • Journal • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CDKN2A • EGFR • KRAS

From Gefitinib to Amivantamab: Progress and Perspectives of Therapies Targeting the Epidermal Growth Factor Receptor in the Era of Precision Oncology. (PubMed, J Cancer Prev) - "This review provides a comprehensive overview of the evolution of four generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs): first-generation reversible inhibitors such as gefitinib and erlotinib; second- and third-generation irreversible inhibitors, including afatinib, dacomitinib, and osimertinib; and emerging fourth-generation agents, such as amivantamab. Future studies should explore combination therapies, antibody-drug conjugates, and next-generation allosteric inhibitors as promising strategies to overcome resistance. The evolution of EGFR-targeted therapy exemplifies the progress of precision oncology and serves as a basis for designing new paradigms in the management of lung cancer."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

ANALYZING CLINICAL TRIAL DISCONTINUATION REASONS FOR ADVANCED EGFR-DRIVEN NON-SMALL CELL LUNG CANCER (WRMC 2026) - "FDA-approved drugs in the terminated trials for "EGFR" noticed in the sample include Erlotinib (Tarceva) (OSI-774), Afatinib (Gilotrif), Osimertinib (Tagrisso), and Dacomitinib (Vizimpro). Clinical trials are often terminated due to company/business decisions or low patient accrual. Careful analysis of these factors is essential to reduce the risk of premature discontinuation, particularly in NSCLC studies where many trials involve experimental therapies with significant future potential. By addressing these challenges proactively, we can help ensure that promising treatments are not lost before their benefits are fully realized."

Clinical • Metastases • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Targeting EGFR With Indole Derivatives: Recent Advances and Therapeutic Perspectives. (PubMed, Chem Biodivers) - "The translation potential of this scaffold is also supported by the clinical success of indole-based EGFR inhibitors, including the third-generation drug osimertinib. This paper summarizes the relevant literature of indole EGFR inhibitors published between 2021 and 2025, which may include mechanistic insights, biological screening, and therapeutic potential. The indole scaffold can be a useful starting point to push forward the next generation of targeted cancer therapies."

Journal • Review • Oncology • EGFR

A deep state-space analysis framework for cancer patient latent state estimation and classification from EHR time-series data. (PubMed, PLoS One) - "Significant features were also confirmed, such as immune cell abnormalities, which are poor prognostic factors in patients treated with Nivolumab, Osimertinib, and Afatinib. This technological innovation deepens our understanding of disease progression and supports early treatment adjustments, prognostic evaluations, and the formulation of optimal long-term strategies. With the advancements in deep learning, its application in healthcare has even greater potential."

Journal • Hematological Disorders • Oncology

Case Report: A patient harboring rare EGFR S768I/V769L compound mutation benefited from afatinib and osimertinib. (PubMed, Front Pharmacol) - "After multi-disciplinary treatment, the patient received concurrent chemoradiotherapy with pemetrexed and cisplatin, and achieved partial response. This patient did not receive durvalumab immunoconsolidation therapy for economic reasons...Patients with EGFR S768I/V769L compound mutated NSCLC may benefit from afatinib and osimertinib. Drugs with strong brain penetration capabilities are still needed for patients with S768I/V769L compound mutation to further improve survival outcomes."

Journal • Cough • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Respiratory Diseases • Solid Tumor • EGFR

Restoring osimertinib sensitivity in EGFR-mutant NSCLC: the role of anlotinib in modulating Wnt/β-catenin/YAP pathways. (PubMed, Am J Cancer Res) - "In vivo, anlotinib reduced tumor growth in Sh-PD-L1-OR models (P < 0.01), with decreased expression of EGFR, PD-L1, YAP, and β-catenin. These findings suggest that high PD-L1 expression promotes osimertinib resistance through activation of YAP and Wnt/β-catenin, and that anlotinib combined with osimertinib can reverse resistance by restoring GSK3β activity, activating the Hippo pathway, and inhibiting β-catenin signaling."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A Study of SKB264 (MK-2870; Sac-TMT) for the Treatment of Participants With Advanced or Metastatic Non-small Cell Lung Cancer (SKB264-II-04) (MK-2870-003) (clinicaltrials.gov) - P2 | N=356 | Active, not recruiting | Sponsor: Klus Pharma Inc. | Trial primary completion date: Dec 2025 ➔ Jun 2026

Monotherapy • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

A ctDNA-guided Phase II Trial of Osimertinib in Combination With Sacituzumab Tirumotecan in EGFR-mutated Advanced NSCLC Patients With Positvie ctDNA After lead-in Osimertinib Monotherapy (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Guangdong Association of Clinical Trials

Circulating tumor DNA • Monotherapy • New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A combined strategy of EGFR-MET bispecific antibody and HER3 ADC to overcome osimertinib resistance in NSCLC. (PubMed, Cell Oncol (Dordr)) - "In conclusion, we have proposed a new therapeutic strategy for NSCLC after osimertinib resistance. The combined strategy of amivantamab and patritumab deruxtecan highlight a promising therapeutic avenue, warranting future clinical trials to validate safety and efficacy."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3

From class effects to specificity FAERS evidence and network mapping of adverse events in NSCLC targeted therapy. (PubMed, Int J Surg) - "This first NSCLC-focused FAERS comparison integrating four-method signal detection with network analysis delineates reproducible class effects superimposed by drug-specific toxicities. Findings support tailored monitoring (e.g., dermatologic care for EGFR-TKIs; ECG/electrolytes for osimertinib; lipid/CK surveillance for ALK-TKIs; blood pressure/liver testing for RET-TKIs) to inform risk-aware first-line decisions."

Adverse events • Journal • Cardiovascular • Dyslipidemia • Hypertension • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • ROS1

TATTON: AZD9291 in Combination With Ascending Doses of Novel Therapeutics (clinicaltrials.gov) - P1 | N=344 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Targeting driver mutations in lung cancer with interstitial pneumonia: A nationwide study in Japan. (PubMed, Eur J Cancer) - "Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival."

Journal • Fibrosis • Infectious Disease • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • BRAF • EGFR • KRAS • MET

Data analytics for real-world data integration in TKI-treated NSCLC patients using electronic health records. (PubMed, ESMO Real World Data Digit Oncol) - "Patients were treated in first-line (1L) with osimertinib or other TKIs (non-osimertinib). This study demonstrates that real-world treatment patterns and outcomes of TKIs are comparable with those found in both clinical trials and other real-world studies. RWE studies can support clinicians in investigating the best treatment strategy and decision makers to drive new health policies."

Journal • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

JIN-A02, a Mutant-Selective Fourth-Generation EGFR inhibitor, Overcomes C797S-Mediated Resistance and Demonstrates Intracranial Activity in NSCLC. (PubMed, Clin Cancer Res) - "These findings highlight JIN-A02 as a promising therapeutic strategy to overcome C797S- and T790M-mediated resistance in EGFR-mutant NSCLC, including intracranial disease, and support its further clinical development."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Lineage Plasticity: An Emerging Mechanism of Acquired Resistance to Cancer Therapy (LCC 2026) - "A clear demonstration of the power of this approach came with the discovery of the BCR-ABL T315I gatekeeper mutation that confers resistance to the ABL kinase inhibitor imatinib (Gleevec) in patients with chronic myeloid leukemia...These and other examples have proven instructive in designing next generation inhibitors that limit or restrict the potential for "on target" escape mechanisms, with asciminib (for CML) and osimertinib (for EGFR mutant lung cancer) serving as instructive examples...Much attention is now focused on unraveling the series of genetic and epigenetic events that enable tumor cells to undergo such a dramatic identity change, with current evidence pointing to a reawakening of long silenced developmental pathways (largely driven by transcription factors). I will discuss our efforts to unravel the molecular details of the adeno-to-neuroendocrine transition in prostate cancer, focusing on opportunities for therapeutic intervention."

Preclinical • Chronic Myeloid Leukemia • Endocrine Cancer • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Lung Adenocarcinoma • Lung Cancer • Melanoma • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • ABL1 • BCR