Tagrisso (osimertinib) / AstraZeneca - LARVOL DELTA

REVIVE: Osimertinib Combined With Chemotherapy in Patients Who Had Distant Recurrence After Adjuvant Osimertinib for EGFRm Resectable SIB-IIIA NSCLC. (clinicaltrials.gov) - P4 | N=100 | Not yet recruiting | Sponsor: AstraZeneca

Biomarker • New P4 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2) (clinicaltrials.gov) - P2 | N=140 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Oct 2025 ➔ May 2026

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

Osimertinib synergizes selinexor on anti-tumor effect by targeting c-MYC in T-cell acute lymphoblastic leukemia (ASH 2025) - "Conclusions The combination of Osimertinib with Selinexor has synergistic effects on cell proliferation arrest and apoptosis in T-ALL by targeting c-MYC both in vitro and in vivo, providing a promising strategy for overcoming the treatment of T-ALL. Further clinical evaluation is required."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • EGFR • MYC • STAT3 • XPO1

Case Report: Two cases of non-small cell lung cancer with coexistence of NTRK2 fusion and EGFR mutations. (PubMed, Front Oncol) - "Case 1 received osimertinib combined with savolitinib, had 33 months of follow-up, and achieved a partial response. Case 2 received furmonertinib and achieved a complete response. NTRK2 fusion coexisting with EGFR mutations is a rare molecular characteristic of non-small cell lung cancer, accompanied by positive PD-L1 expression, and may serve as a promising biomarker for targeted therapy."

IO biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FGFR1 • MET • Napsin A • NKX2-1 • NTRK2 • PD-L1 • TMB

Osimertinib (osi) before and after chemoradiotherapy (CRT) in patients (pts) with unresectable (UR) stage III EGFRm NSCLC: Phase II NEOLA study interim analysis (IA) (ESMO Asia 2025) - P2, P3 | "Osi induction did not prevent receipt of definitive CRT in pts with UR stage III EGFRm NSCLC; safety was consistent with the known safety profiles of osi and CRT."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety profile and anti-tumor efficacy of VRN110755, a highly selective, brain penetrant EGFR inhibitor for patients with EGFR-driven non-small cell lung cancer (ESMO Asia 2025) - "The target engagement (Ctrough/IC50) of 320mg VRN110755 against EGFR common mutations was 4 times higher than that of 80 mg Osimertinib. In phase 1a study, VRN110755 demonstrates favorable PK, CNS penetration, and a differentiated safety profile. Robust antitumor activity in heavily pretreated, C797S-positive, and/or BM patients, supporting the potential of VRN110755 as a promising best-in-class EGFR inhibitor."

Clinical • Late-breaking abstract • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer

Overall survival for amivantamab plus lazertinib vs osimertinib in Asian participants with first-line EGFR-mutant advanced NSCLC: MARIPOSA subgroup analysis (ESMO Asia 2025) - P3 | "Consistent with the overall population, ami+laz meaningfully reduced the risk of death vs osi among Asian pts with 1L EGFRm advanced NSCLC and is projected to provide an OS benefit of >12 mo. These results among Asian pts confirm the findings from the overall MARIPOSA population, establishing ami+laz as a new SoC."

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

A 66-Year-Old Woman with EGFR-Mutant Lung Adenocarcinoma and Brain Metastases Achieving 96-Month Overall Survival with serially deploying three distinct third-generation EGFR-TKIs (ESMO Asia 2025) - "First-line icotinib plus paclitaxel/nedaplatin was given and achieved PR and 36-month PFS...Osimertinib 80mg qd combined with pemetrexed chemotherapy for 5 cycles, followed by osimertinib monotherapy, yielded 25-month PFS until isolated CNS progression. Despite concomitant whole-brain radiotherapy and bevacizumab with Osimertinib, intracranial lesions advanced...This exceptional survival in advanced EGFR+ NSCLC was achieved through initial chemo-TKI therapy, sequential third-generation TKIs (osi→almo→furmo) for CNS control, and furmonertinib dose escalation for late CNS progression. The persistent TP53 co-mutation suggests a resistance mechanism, while PD-L1 negativity excluded immunotherapy, demonstrating the efficacy of optimized TKI sequencing alone."

Clinical • IO biomarker • Brain Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • TP53

Aumolertinib as an effective alternative in osimertinib-intolerant advanced NSCLC with liver cirrhosis: a case report (ESMO Asia 2025) - "This case suggests that aumolertinib may be a viable alternative for patients who are intolerant to osimertinib."

Case report • Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Platinum-Pemetrexed Plus Osimertinib Beyond Progression Achieves Complete Metabolic Response in EGFR Exon 19-Deleted Metastatic NSCLC (ESMO Asia 2025) - "He received cisplatin 75mg/m2 and pemetrexed 500mg/m2 3 weekly for 4 cycles with continued osimertinib. Novel targeted agents and ADCs show promise. Ongoing trials, COMPEL and FLAME are assessing chemotherapy plus osimertinib beyond progression or in early ctDNA persistence."

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EGFR • KRAS • PIK3CA

A new paradigm of using combination of osimertinib with chemotherapy for first-line treatment in EGFR mutated metastatic non-small cell lung cancer: A real-world Indian experience (ESMO Asia 2025) - "Real world data from India is limited. This is a retrospective, single-centre study, conducted from August 2021 to July 2025, which included patients with newly diagnosed EGFR-mutated (exon19 deletion or exon21 L858R) mNSCLC who received osimertinib combined with chemotherapy (pemetrexed plus carboplatin) for 4 cycles followed by maintenance osimertinib, with or without pemetrexed. Osimertinib combined with chemotherapy has demonstrated a longer PFS compared to historical data in our patient cohort. While it is associated with higher toxicity, these are generally clinically manageable. With the recently reported OS benefit from the FLAURA2 trial, this regimen is poised to become a standard of care for EGFR-mutated NSCLC, particularly in patients with a high disease burden, brain metastases, or EGFR-L858R mutations."

Clinical • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KEAP1 • PIK3CA • RB1 • TP53

EGFR exon 19 duplications/insertions, rare but potential therapeutic targets for NSCLC: A real-world study and pooled analysis of case series (ESMO Asia 2025) - "Stratified by treatment, mPFS1 was 15.5 months with erlotinib (IQR: 9.4-20.0), 12.3 months with afatinib (IQR 7.8-14.3), 7.8 months with osimertinib (IQR 5.6-9.4), 10.9 months with icotinib (IQR 5.9-12.6), 5.3 months with gefitinib (IQR 4.7-9.2), and 6.0 months with immuno/chemotherapy (IQR 3.9-9.0). E19dup/ins are exceedingly rare EGFR genomic alterations with 4 variants reported to date. There is a potential PFS benefit with the use of erlotinib over immuno/chemotherapy as first-line treatment for these mutations. Further data are required to confirm the role of erlotinib in this setting."

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

Comparative clinical efficacy of osimertinib versus erlotinib in stage IV EGFR and TP53 co-mutated lung adenocarcinoma (ESMO Asia 2025) - "Osimertinib demonstrated superior survival outcomes compared to erlotinib in patients with stage IV TP53 and EGFR co-mutated lung cancer. Further studies in larger cohorts are warranted to validate these findings and to explore predictors of response within each treatment group."

Clinical • IO biomarker • Metastases • Lung Adenocarcinoma • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MSI • PD-L1 • TP53

Treatment outcomes and EGFR mutation profiles in stage IV NSCLC patients with brain metastases: Insights from a Singapore cohort (ESMO Asia 2025) - "Initial ST included Osimertinib (Osi) (68.2%), other tyrosine kinase inhibitors (9.1%), chemotherapy (6.1%), clinical trial (10.6%), and Osi plus chemotherapy (6.1%)... In this cohort, classical EGFR mutations were common, with osi-based systemic therapy as the mainstay. CT trended towards longer CNS PFS, particularly in pts with fewer BM and classical mutations. ST alone gave favourable CNS PFS in pts with BMs < 1cm, though differences were not statistically significant."

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

Clinical outcomes and discontinuation patterns of osimertinib in metastatic lung adenocarcinoma: A Real-world cohort study (ESMO Asia 2025) - "Extended treatment duration and absence of adverse events were positively correlated with favorable therapeutic response. High rates of discontinuation due to death and financial limitations underscore the need for early intervention and improved access to care. These findings support the importance of individualized treatment planning and proactive management of toxicity in lung cancer therapy."

Clinical • Clinical data • Metastases • Real-world • Real-world evidence • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

De novo and acquired MET amplification in patients (pts) with non-small cell lung cancer (NSCLC) treated with tepotinib: Results from a real-world data analysis in Australia (ESMO Asia 2025) - "In INSIGHT 2 (DCO: Mar 28, 2023), 98 pts with EGFR-mutant lung cancer and acquired METamp (in tissue by fluorescence in situ hybridization [FISH]) were treated with osimertinib and tepotinib; ORR was 50.0% (95% CI 39.7–60.3) and mPFS was 5.6 mths (95% CI 4.2–8.1). Analysis of pts in the Australian cost-share program showed that tepotinib is an effective and tolerable tx in MET-amplified NSCLC."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • MET • RET • TP53

Analysis of the efficacy and safety of radioactive seed Implantation combined with EGFR-TKI in the first-line treatment of classical EGFR mutation NSCLC (ESMO Asia 2025) - "Background: Representative EGFR-TKIs, such as gefitinib, afatinib, and osimertinib, have become the first-line standard treatment for patients with classical EGFR mutations (exon 19 deletions and exon 21 L858R) non-small cell lung cancer, with PFS ranging from 10 to 20 months...PFS has not yet reached for those receiving 2nd agents (only two patients, both treated with dacomitinib, still in follow-up currently), and 39.9m for those receiving 3rd agents. EGFR-TKI therapy combined with RSI confers a significant PFS benefit and merits further prospective investigation."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TP53

Therapeutic drug monitoring guided real world clinicopharmacological evaluation of thrice weekly osimertinib plus chemotherapy in EGFR-mutant advanced NSCLC: Phase II safety and efficacy study (ESMO Asia 2025) - "Thrice-weekly osimertinib combined with chemotherapy demonstrates robust clinical activity and manageable toxicity in the real-world first-line treatment of metastatic EGFRm NSCLC. These findings suggest comparable efficacy to standard daily dosing and support the rationale for future dose-de-escalation trials to optimize treatment cost and toxicity without compromising efficacy."

Clinical • Metastases • P2 data • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A molecular trojan horse in the treatment odyssey: Navigating the landscape of resistance and brain metastasis in EGFR mutant NSCLC (ESMO Asia 2025) - "Background: First-line osimertinib is standard for advanced EGFR-mutant NSCLC, yet resistance is inevitable... Baseline and progression NGS identified diverse resistance pathways, with TP53/RB1/PTEN possibly linked to transformation. Most CNS events occurred early, underscoring the value of baseline MRI and vigilant surveillance. Integration of NGS and CNS imaging may refine patient selection for single-agent versus combination strategies such as FLAURA2 or MARIPOSA."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • NTRK • NTRK2 • PI3K • PIK3CA • PTEN • RB1 • TP53

Efficacy and safety of erlotinib and ramucirumab combination therapy in patients harboring EGFR mutations who have previously received osimertinib treatment for non-small cell lung cancer: CS-Lung006 Study (ESMO Asia 2025) - "In patients who received prior treatment with osimertinib, combination therapy with erlotinib and ramucirumab was suggested to be an effective treatment option when osimertinib treatment was discontinued due to toxicity."

Clinical • Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Cancer therapy-related cardiac dysfunction associated with EGFR-TKIs in advanced EGFR-mutant non-small cell lung cancer: A single-center prospective observational study (ESMO Asia 2025) - "Global longitudinal strain (GLS), tricuspid regurgitation peak gradient (TRPG), E/e′ ratio, Troponin-T and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), were also analyzed using generalized estimating equations. Among 100 patients included in this study (median age 64; 39.0% male, 61.0% female; 72.0% non-smokers), 66.0% patients received osimertinib, 16.0% received erlotinib, 13.0% received afatinib, and 5.0% received dacomitinib. Our study demonstrates the incidence of CTRCD in patients with advanced or recurrent EGFR-mutant NSCLC receiving EGFR-TKI treatment, and compares the effect between osimertinib and first or second generation TKIs. Increased E/e′ ratio was found in osimertinib group, indicating increased diastolic dysfunction. These findings highlight the importance of clinical monitoring of cardiac function in patients receiving TKIs, particularly in those treated with osimertinib."

Clinical • Metastases • Observational data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Prediction of osimertinib response using ultra-sensitive circulating tumor DNA analysis in patients with EGFR mutant non-small cell lung cancer (ESMO Asia 2025) - "This trial met the primary endpoint. Ultra-sensitive ctDNA analysis has the potential to predict outcomes in patients with plasma EGFRm-positive NSCLC receiving osimertinib."

Circulating tumor DNA • Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Osimertinib versus erlotinib plus an angiogenesis inhibitor for patients with EGFR-mutated non-small cell lung cancer and pleural effusion (ESMO Asia 2025) - "PFS of MPE (MPE-PFS), PFS, and overall survival (OS) were calculated using Kaplan-Meier curves, and log-rank tests were performed. Of 421 patients, median age was 73 years [range 28-92], 272 (65%) female, performance status 0 or 1 in 334 (79%) cases, adenocarcinoma in 417 (99%) cases, and 373 (89%) received osimertinib, 48 (11%) received erlotinib plus bevacizumab or ramucirumab (E/VEGF group). In patients with EGFR-mutated NSCLC and MPE, osimertinib was shown to be equally effective as erlotinib plus an angiogenesis inhibitor in controlling MPE."

Clinical • Pleural effusion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Prospective study of aumolertinib in NSCLC patients with EGFR sensitive mutations who are intolerant to osimertinib treatment (ESMO Asia 2025) - P2 | "As the first prospective trial in osimertinib-intolerant patients, Aumolertinib demonstrates sustained efficacy and a favorable safety profile with zero discontinuations/deaths, establishing a new paradigm for toxicity-driven treatment strategies."

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

MET testing and treatment (tx) sequencing after progression of disease (PD) on first-line (1L) osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and acquired MET overexpression and/or amplification (OverExp/Amp): Final analysis of a global real-world (rw) study (ESMO Asia 2025) - P2 | "Background: In the phase II SAVANNAH study (NCT03778229), osi 80 mg QD + savolitinib 300 mg BID demonstrated clinically meaningful and durable responses in EGFRm advanced NSCLC with MET OverExp/Amp after PD on 1L osi...MET-TKIs (tepotinib 52%, capmatinib 31%) and EGFR-TKIs (osi 91%) were the most common 2L txs (29% and 24%), followed by chemotherapy (CT 20%; most frequently platinum doublet 73%)... In this rw analysis, most pts had acquired MET Amp detected with NGS and limited detection of OverExp/Amp with IHC/FISH, likely indicating underutilisation of these assays. MET-TKIs and 3rd-gen EGFR-TKIs were most commonly used following PD on 1L osi and in pts with high MET cutoffs."

Clinical • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor