Gilotrif (afatinib) / Boehringer Ingelheim - LARVOL DELTA

Anti-Tumor Activity of BH-30643, a Novel Macrocyclic EGFR TKI, in Patients With Secondary EGFR Resistance Mutations (IASLC-WCLC 2026) - P1/2 | "Responses were observed across different C797S co-mutations (e.g., exon 19 del, L858R, G719S, T790M) and following different targeted therapies (e.g., osimertinib, afatinib, amivantamab). Conclusions : BH-30643 can achieve clinical and molecular responses in heavily pretreated NSCLC patients with secondary EGFR resistance mutations across diverse molecular contexts, supporting its potential as monotherapy in the treatment of resistance to 3rd-generation EGFR TKIs. Expansion cohort enrollment is ongoing with a focus on C797S-positive resistance."

Clinical • First-in-human • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • KRAS • MET

Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy in Relapsed/Refractory EGFR-mutant NSCLC (IASLC-WCLC 2022) - P1 | " The LACP (lazertinib, amivantamab, carboplatin, pemetrexed) cohort of the CHRYSALIS-2 study (NCT04077463) enrolled patients with EGFR-mutant NSCLC whose disease progressed on or after treatment with an EGFR TKI as last line of therapy (maximum of 3 prior lines)... Enrolled patients have received a median of 2 (range, 1-3) prior lines of therapy, including osimertinib (n=14), gefitinib (n=3), and afatinib (n=3)... Amivantamab in combination with lazertinib and chemotherapy yielded high overall response rates in patients who progressed on EGFR TKIs as prior line of therapy. The safety profile of the LACP regimen was consistent with the individual agents, with no evidence of new safety signals or additive toxicity."

Combination therapy • Fatigue • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • EGFR

Overall survival of first-line amivantamab plus lazertinib in atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC): Updated results from the CHRYSALIS-2 study. (ASCO 2026) - P1 | "Afatinib, approved for atypical EGFR-mutated NSCLC, showed a median overall survival (OS) of 19.4 months among 38 participants (pts) with atypical EGFR-mutations globally (Yang Lancet Oncol 2015)...In MARIPOSA, first-line (1L) ami plus lazertinib (ami-laz) significantly prolonged OS vs osimertinib (HR, 0.75; P=0.005) in cEGFR-mutated NSCLC... 1L treatment of atypical EGFR-mutated advanced NSCLC with ami-laz resulted in a clinically meaningful median OS of nearly 3.5 years. Many pts were able to stay on 1L treatment long term, with 20% still ongoing. Ami-laz has now shown substantial survival benefit in both 1L cEGFR- and atypical EGFR-mutated disease."

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

Amivantamab in combination with lazertinib in patients with atypical epidermal growth factor receptor (EGFR) mutations excluding exon 20 insertion mutations: Initial results from CHRYSALIS-2 (ESMO Asia 2022) - P1 | "Afatinib is the only EGFR tyrosine kinase inhibitor (TKI) approved to treat these mutations. No new safety signals or concerns were identified. Conclusions Among a patient population with few treatment options, amivantamab combined with lazertinib demonstrated encouraging anti-tumor activity in a majority of patients with a tolerable safety profile."

Clinical • Combination therapy • EGFR exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Operationalizing the PMMR Standardized Framework to Manage Patients on TKIs for Non-Small Cell Lung Cancer (NSCLC) (IASLC-WCLC 2026) - "Firstly, TA AE data was collected (Osimertinib, Amivantamab-Lazertinib, Sunvozertinib, Crizotinib, Alectinib, Afatinib, Entrectinib, Selpercatinib, Lorlatinib) based on clinical trial data, regulatory drug labels, and provincial/national guidelines. Details, including barrier and facilitators, and recommendations on implementation will be presented at the conference. Conclusions : To further enhance adherence and treatment efficacy, future directions include: (i) integrating a grading criterion for nurses in the EMR while using the scripts to enhance assessment and (ii) creating a remote monitoring application that leverages PMMR."

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

Amivantamab plus lazertinib in atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC): Results from CHRYSALIS-2. (ASCO 2024) - P1 | "Research Funding: Janssen Global Services LLC. In the largest, single-cohort, prospective study of atypical EGFR-mutated advanced NSCLC, ami+laz demonstrated clinically meaningful and durable antitumor activity in pts who were treatment-naïve or had disease progression on afatinib."

Metastases • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR

Synergistic antitumor effects and molecular mechanisms of pirfenidone combined with osimertinib/afatinib in non-small cell lung cancer (ERS 2026) - "Pirfenidone potentiated EGFR-TKIs via a dual mechanism: inhibition of the p38γ–PI3K/AKT/mTOR pathway and induction of p38γ-independent autophagic flux. p38γ-driven PI3K/AKT/mTOR activation may contribute to osimertinib resistance. Pirfenidone re-sensitized resistant cells to osimertinib, supporting its potential use as an EGFR-TKI sensitizer to overcome targeted-therapy resistance."

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

Sequential afatinib (AFA) to osimertinib (OSI) in EGFR-mutant non-small cell lung cancer (NSCLC): Five-year analysis of Gio-Tag Japan, a multicenter prospective observational study (ESMO 2026) - No abstract available

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

Efficacy of afatinib in patients with advanced/metastatic solid tumors harboring NRG1 gene fusions: A novel, prospective real-world outcomes study based on single-patient protocol data. (ASCO 2022) - P=N/A | "Safety will also be assessed. The study is open for recruitment."

Clinical • Real-world evidence • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGF • ERBB3 • NRG1

Afatinib versus chemotherapy for treatment-naïve non-small cell lung cancer with a sensitizing uncommon epidermal growth factor receptor mutation: A phase III study (ACHILLES/TORG1834) (ESMO 2023) - "Methods In this open-label phase III study, treatment-naïve patients with sensitizing uncommon EGFR mutant NSCLC were randomized 2:1 to oral afatinib (30 or 40 mg daily) or the combination of platinum (cisplatin 75 mg/m2 or carboplatin AUC 5 or 6) and pemetrexed (500 mg/m2), followed by pemetrexed maintenance therapy every three weeks. One treatment related death due to pneumonitis was observed in the afatinib arm. Conclusions Afatinib is superior to platinum doublet chemotherapy as an initial treatment for uncommon or compound EGFR mutation-positive advanced NSCLC."

Late-breaking abstract • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Afatinib in patients with solid tumors with neuregulin 1 (NRG1) fusions: a case series from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. (PubMed, ESMO Open) - "Though the sample size was small, afatinib demonstrated promising activity in patients with advanced solid tumors with NRG1 fusions, including durable DC warranting additional study."

Journal • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • NRG1

Decentralized, Real-World Study of Afatinib in Patients with Advanced/Metastatic Solid Tumors with NRG1 Fusions (IASLC-NACLC 2022) - P=N/A | "Oncologist. 2021; 26(1):7–16."

Clinical • Real-world evidence • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NRG1

Integrating clinical outcomes with molecular simulations to guide the selection of non-classical EGFR-TKIs: A comprehensive analysis and development of treatment strategies. (PubMed, Exp Ther Med) - "Clinical outcomes varied by mutation subtype and EGFR-TKI regimen; relatively favorable progression-free survival (PFS) was observed with dacomitinib in L861Q and with afatinib- or dacomitinib-based treatment in selected S768I compound mutations. Exploratory Spearman analysis suggested that lower docking scores and more negative MM-GBSA ∆G_bind values were associated with longer PFS. These findings provide hypothesis-generating evidence that molecular simulation may help inform personalized EGFR-TKI selection for non-classical EGFR mutations, although validation in larger, consecutive and prospective multicenter cohorts is required."

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

The first report of K-Umbrella Gastric Cancer Study: An open label, multi-center, randomized, biomarker-integrated trial for second-line treatment of advanced gastric cancer (AGC). (ASCO 2022) - P=N/A | "In the biomarker group, patients were treated with specific targeted agents in combination with weekly paclitaxel; 1) EGFR 2+/3+ patients for pan-ERBB inhibitor (afatinib; EGFR cohort), 2) PTEN loss/null (H-score <100) patients for PIK3Cβ inhibitor (GSK2636771; PTEN cohort), and 3) PD-L1+, dMMR/MSI-high, or EBV-related cases for anti-PD-1 inhibitor (nivolumab; NIVO cohort). Control group and NONE cohort in biomarker group without predefined biomarkers were treated with SOC (weekly Paclitaxel±Ramucirumab)... Considering the characteristics of umbrella design with multiple biomarkers having different biological roles, biomarker group did not show the improved survival over control arm with these 3 drugs. For optimal biomarker-driven targeted agent applications, NGS-based biomarker driven K-Umbrella GC-2 study is ongoing."

Biomarker • Clinical • IO biomarker • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • HER-2 • PD-L1 • PIK3CB • PTEN

An ancillary study of the BIOMEDE trial using patient-derived cellular models to predict therapeutic response and disease dissemination in diffuse midline glioma (EANO 2026) - "Drug sensitivity was evaluated using viability-based assays across a panel of clinically relevant compounds including everolimus, ONC201/206, afatinib, trametinib and niraparib. This ancillary study establishes a comprehensive functional platform based on BIOMEDE-derived patient models, with the aim of enhancing and refining the biological and clinical insights generated by the trial. Ongoing molecular analyses will further characterize transcriptional programs underlying these functional phenotypes and support integrated analyses combining functional, molecular, and clinical data."

Clinical • Brain Cancer • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Concurrent icotinib and definitive radiotherapy followed by detection of an EGFR exon 20 insertion at disease progression in unresectable stage III EGFR S768I-mutant lung adenocarcinoma: a case report. (PubMed, Front Oncol) - "Subsequent treatment with afatinib, ivonescimab plus chemotherapy, and sunvozertinib was selected according to dynamic molecular profiling. More importantly, it highlights the value of repeat biopsy and comprehensive genomic profiling for interpreting molecular changes at disease progression and guiding subsequent individualized treatment in patients with uncommon EGFR mutations. However, these observations are derived from a single case and require validation in larger prospective studies."

Journal • Lung Adenocarcinoma • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

A phase II study of DFP-14323, a non-specific immunomodulator, in combination with low-dose afatinib as first-line therapy for common EGFR mutation-positive NSCLC. (PubMed, Ther Adv Med Oncol) - "The combination of DFP-14323 and low-dose afatinib was considered to have the potential for future clinical utility for EGFR mutation-positive NSCLC. As the next step, a study evaluating this combination therapy in uncommon EGFR mutation-positive NSCLC is currently underway in Japan (jRCT2061230111)."

Journal • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Interstitial Lung Disease • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ANPEP • EGFR

ALPACCA: Ph3 Trial of Firmonertinib vs Investigator's Choice of EGFRI as 1L Treatment for Locally Advanced or mNSLC With EGFR PACC Mutations (IASLC-WCLC 2026) - P3 | "Treatment options include EGFR tyrosine kinase inhibitors (TKIs) (osimertinib, afatinib) and chemotherapy.EGFR PACC mutations comprise approximately 12.5% of all NSCLC EGFR mutations (Robichaux et al 2021, Nilsson et al 2024). Key secondary endpoints include OS, investigator assessed PFS and ORR, and safety and tolerability. Enrollment is ongoing."

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

Uncommon EGFR mutations conducted with osimertinib in patients with NSCLC (UNICORN): A phase 2 study. (ASCO 2023) - "Key drugs for metastatic NSCLC (mNSCLC) uC-EGFRm are limited, with only afatinib being FDA approved. Osimertinib in mNSCLC pts harboring uC-EGFRm other than exon 20 insertions showed clinical activity with manageable toxicities. These results suggest that osimertinib can be considered as a treatment option for this specific population. Clinical trial registration: jRCTs071200002."

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

NGS-Based Risk Stratification for First-Line EGFR-TKI Selection inEGFR-Mutant NSCLC: A Multicenter Real-World Study (IASLC-WCLC 2026) - "While osimertinib demonstrated superior PFS in low-risk patients, afatinib showed a trend towards superior PFS in high-risk ones. These findings support a risk-adapted treatment strategy and highlight the potential role of clinicogenomic profiling in refining first-line EGFR-TKI selection in real-world clinical practice."

Clinical • IO biomarker • Next-generation sequencing • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • PD-L1 • PI3K • TP53

A phase 2, single arm, European multi-center trial evaluating the efficacy of afatinib as first line or later line treatment in advanced chordoma. (ASCO 2024) - P2 | "With a PFS rate at 12 mos of 40.0% in the first-line cohort and 38.5% at 9 mos in the further-line cohort, this phase 2 study met the PFS endpoint. QoLQ data will be provided at the conference . Partial response by RECIST was seen in 4/43 pts."

Clinical • IO biomarker • Metastases • P2 data • Cardiovascular • Chordoma • Hypertension • Mucositis • Pain • HER-2

Intracranial Outcomes and Treatment Response in HER2 (ERBB2)-Mutated Non-Small Cell Lung Cancer With Brain Metastases (IASLC-WCLC 2026) - "The median time to intracranial progression for patients who had active progressive brain metastases prior to the start of a given therapy was 7.4 months for pemetrexed-based regimens, 3.2 months for trastuzumab deruxtecan (T-DXd), and 1.6 months for other HER2 targeted therapies (eg, trastuzumab, TDM-1, afatinib)...Conclusions : Pemetrexed-based therapies and T-DXd each achieved only modest CNS disease control in this cohort, and intracranial progression as well as development of LMD were common in patients with existing brain metastases, despite most patients receiving radiation as well. Therapies with better CNS activity for HER2-mutated NSCLC are therefore needed, potentially with newly-approved tyrosine kinase inhibitors such as zongertinib and sevabertinib."

CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

On-Target Acquired Resistance to Zongertinib and Strategy to Overcome It - in Vitro Study usingHER2ex20 Insertion Models (IASLC-WCLC 2026) - "Methods : We examined efficacy of zongertinib, sevabertinib and other TKIs with HER2 inhibitory activity (erlotinib, afatinib, poziotinib, mobocertinib, and osimertinib) using murine pro-B-cell line (Ba/F3) models harboring one of three most common HER2 exon 20 insertions (A775_G776insYVMA (YVMA), G776delinsVC (VC) and P780_Y781insGSP (GSP)). Conclusions : These findings indicate that distinct compound mutations confer differential resistance to HER2-TKIs depending on the original HER2 exon 20 insertion. Zongertinib-resistant mutations, such as YVMA+S783A and GSP+G776C, remained sensitive to poziotinib, whereas compound mutations associated with poziotinib resistance, including YVMA+C805S and VC+C805S, were effectively inhibited by sevabertinib."

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

Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1). (PubMed, Br J Cancer) - P2 | "An exploratory biomarker analysis suggested that basal-squamous tumours and ERBB2 amplification were associated with superior response to afatinib."

Journal • Metastases • P2 data • Acute Coronary Syndrome • Cardiovascular • Genito-urinary Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Urothelial Cancer • EGFR • HER-2

Retrospective Analysis of Treatment Outcomes for T-DM1 (Trastuzumab Emtansine) following T-DXd (Trastuzumab Deruxtecan) and T-DXd following T-DM1 in HER2-Mutated Non-Small Cell Lung Cancer (IASLC-TTLC 2025) - "Two patients received T-DM1 combined with afatinib. The efficacy of T-DM1 in T-DXd treated HER2-mutant NSCLC is limited, with only a small percentage of patients achieving durable benefit. Novel therapies for this population are needed. In contrast, T-DXd appears more effective after prior T-DM1 in HER2-mutant NSCLC."

Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2