Vizimpro (dacomitinib) / SFJ Pharma, Pfizer - LARVOL DELTA

Over 200! The largest BaF3-EGFR engineering cell lines collection, a useful platform for novel drug discovery (AACR 2025) - "Recognizing EGFR as a driver gene has accelerated the development of targeted anticancer therapies, such as monoclonal anti-EGFR antibodies (cetuximab, panitumumab) and small molecule receptor tyrosine kinase inhibitors (TKIs). The first generation of EGFR TKIs, like gefitinib and erlotinib, specifically target mutations such as L858R and exon 19 deletions. To address resistance to these early inhibitors, second-generation EGFR TKIs (afatinib, dacomitinib) were developed...Osimertinib, a third-generation TKI, was approved for use in EGFR-mutated NSCLC following the failure of first- and second-generation TKIs, although the EGFR C797S mutation limits its effectiveness. Fourth-generation EGFR TKIs, including BLU-945 and BBT-176, are under clinical evaluation but are not yet approved.We have created more than 200 Ba/F3-EGFR engineered cell lines, making this the largest in vitro and in vivo platform for drug discovery with the widest range of mutant cells. These cell lines..."

Preclinical • Brain Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • EGFR • EPGN • ERBB3 • ERBB4 • HBEGF • HER-2 • TGFA

ERBB4 upregulation in a taxol-resistant triple-negative breast cancer cell line (AACR 2025) - "Treatment of the cells with ERBB inhibitors, sfatinib, allitinib, or PF299804, in sub-lethal concentration only induced a small additive effect on paclitaxel cytotoxicity in MDA-MB-231 cells, but dramatically enhanced paclitaxel cytotoxicity in T50RN cells. These results suggest that ERBB4 may play a critical role in paclitaxel resistance in T50RN cells. Further elucidation of how ERBB4 is induced in T50RN cells and how ERBB4 regulates cell resistance might provide leads to overcome paclitaxel resistance."

Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ERBB3 • ERBB4 • HER-2

Inter-Ethnic Differences in the Efficacy and Safety of Tyrosine Kinase Inhibitors Used in Oncology: Insights From Phase 3 Clinical Trials. (PubMed, Clin Transl Sci) - "Twelve (16%) of the analyses investigating the efficacy of afatinib, brigatinib, dacomitinib, gilteritinib, lorlatinib, neratinib, osimertinib, or pazopanib were assessed to report population differences in PFS and/or OS...The majority of clinical trials noted no clinically remarkable differences in safety between subpopulations; however, for brigatinib, crizotinib, pazopanib, and sunitinib, distinct patterns of adverse events were reported in the Asian and non-Asian subgroups. The underrepresentation of specific subpopulations, the grouping together of results of diverse subpopulations, as well as inconsistencies in the definition and reporting of participant ethnicity/ancestry are barriers to the meaningful exploration of inter-ethnic differences in TKI response. Therefore, further insight into the associations between ethnicity/ancestry and TKI response will require an increase in the diversity of clinical trial participants and appropriate analysis and reporting of..."

Journal • P3 data • Review • Oncology

Analytical Approaches to Estimate Medication Persistence From Electronic Health Record Data: A Study of Tyrosine Kinase Inhibitors in Patients With Epidermal Growth Factor Receptor-Positive Advanced Non-Small Cell Lung Cancer (ISPOR 2025) - "This study compared approaches for estimating the persistence of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), including erlotinib, gefitinib, dacomitinib, afatinib, osimertinib, and lazertinib, among patients with EGFR-positive advanced non-small cell lung cancer (advNSCLC). This retrospective study used the nationwide Flatiron Health EHR-derived deidentified database with a data cutoff of November 30, 2024. The non-TTE approach estimated higher EGFR TKI persistence than the TTE approach at all timepoints. The TTE approach accounts for censoring and estimates cumulative persistence, whereas the non-TTE approach provides a point-in-time snapshot. The TTE approach may also provide insights into other real-world outcomes, such as real-world treatment duration."

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

A Structural Insight Into Two Important ErbB Receptors (EGFR and HER2) and Their Relevance to Non-Small Cell Lung Cancer. (PubMed, Arch Pharm (Weinheim)) - "To develop treatment for EGFR-related NSCLC, several tyrosine kinase inhibitors (TKIs) were designed: gefitinib, erlotinib, as first-generation; neratinib, dacomitinib as second-generation; osimertinib, lazertinib as third-generation, as examples. Although structures obtained so far for the EGFR family provide meaningful insights into the mechanisms, the quality and the quantity of the EGFR family structures are insufficient to elucidate the complete structures and functions to overcome NSCLC. This review evaluates the structures of EGFR-HER2 and investigates their relation to NSCLC."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • EGFR • HER-2

First-in-human studies of VRN110755 in NSCLC patients with EGFR mutations: Safety, pharmacokinetics, and early efficacy assessment (AACR 2025) - "Tumor assessments showed >40% tumor shrinkage in a patient with a C797S mutation, who had progressed after dacomitinib and osimertinib, after 4 weeks of 40 mg treatment. Additionally, another patient with a Del19 mutation, who had progressed after afatinib and platimum chemotherapy, demonstrated >20 % tumor shrinkage after 3 weeks of 80 mg treatment.These findings strongly support the translation of preclinical data into early clinical outcomes for VRN110755. In conclusion, the preclinical and early clinical outcomes of VRN110755 highlight its potential as a promising therapeutic option that can address unmet medical needs in advanced EGFR mutated NSCLC, including resistance to current standard-of-care therapies and progression with BM/LM."

Clinical • P1 data • PK/PD data • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Machine-learning-driven optimization of kinase inhibitors to overcome CNS efflux and target breast cancer brain metastases (AACR 2025) - "Despite the improvements in HER2 targeted therapy to rapidly target BCBM, tucatinib and other quinazoline HER2 inhibitors (dacomitinib and gefitinib) possess poor CNS penetration due to P-gp and BCRP efflux. Our results suggest that structural optimization to modulate the physicochemical properties of small molecules is key to identifying potential drug candidates for targeting BCBM. In vivo studies using animal models will be conducted to validate these findings."

Machine learning • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Aurora kinase A inhibition overcomes tolerance to panHER inhibitors in HPV positive HNSCC (AACR 2025) - "We demonstrate that although panHER inhibitors afatinib and dacomitinib more effectively inhibit growth of HPV+ HNSCC cells than do erlotinib or cetuximab, adaptive signaling through the AURKA/PLK1 axis mediates resistance to panHER inhibitors...Indeed, cell viability experiments and clonogenic survival assays demonstrate strong synergy between panHER and AURKA inhibitors, confirmed in xenografted tumor models treated with the second generation AURKA inhibitor VIC-1911 and dacomitinib...In contrast, addition of AURKA inhibition upregulated PLK1 and pPLK1 and cell death markers. These findings indicate that combination therapy with AURKA inhibition will mitigate the adaptability to EGFR and panHER inhibitors previously described for HPV+ HNSCC."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • AURKA • ERBB3 • PLK1

A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer. (PubMed, Cancer Pathog Ther) - "We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Osimertinib is the first choice of treatment with considerable efficacy and safety for EGFR mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively."

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

Special Investigation for VIZIMPRO Tablets (Secondary Data Collection Study; Safety and Efficacy of VIZIMPRO Under Japanese Medical Practice) (clinicaltrials.gov) - P=N/A | N=40 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Aug 2026 ➔ Apr 2025 | Trial primary completion date: Aug 2026 ➔ Apr 2025

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

Identification and Characterization of Dacomitinib Metabolites in Rats by Liquid Chromatography Combined With Q-Exactive-Orbitrap High Resolution Mass Spectrometry. (PubMed, Biomed Chromatogr) - "Phase II biotransformation pathways included GSH conjugation and N-acetyl-cysteine conjugation. These findings enhance understanding of dacomitinib's metabolic fate, providing critical insights into its elimination mechanisms, and supporting subsequent evaluation of therapeutic efficacy and safety profiles."

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

Neoadjuvant Targeted Therapy with Dacomitinib in a Stage IIIA Non-Small-Cell Lung Cancer Patient Harboring EGFR G719X: A Case Report. (PubMed, Onco Targets Ther) - "Here, we firstly report that a stage IIIA lung adenocarcinoma patient benefited from chemotherapy and dacomitinib as neoadjuvant targeted therapy based on EGFR G719X mutation, achieving a pathological downstaging and the chance of radical surgical resection. Our case describes dacomitinib use as neoadjuvant targeted therapy for EGFR positive advanced NSCLC and highlights the application of molecular testing for the better treatment decision making."

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

Development of indole hybrids for potential lung cancer treatment - part II. (PubMed, Future Med Chem) - "Moreover, indole hybrids osimertinib, mobocertinib, cediranib, and vizimpro are currently applied in clinics for lung cancer therapy, demonstrating that indole hybrids are valuable scaffolds in the treatment and eradication of lung cancer. This review provides a comprehensive overview of the evolving landscape of indole hybrids with the in vitro and in vivo efficacy against lung cancer, and the structure-activity relationships as well as mechanisms of action are also discussed, covering articles published from 2021 onward."

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

Adverse event profiles of EGFR-TKI: network meta-analysis and disproportionality analysis of the FAERS database. (PubMed, Front Pharmacol) - "Afatinib showed highest toxicity; Icotinib was safest...Gefitinib had the strongest signal for interstitial lung diseases; Erlotinib for anorexia...Drugs varied in AE profiles, mostly mild, but Osimertinib and Dacomitinib were associated with more severe events. Osimertinib carried a high cardiac risk, delayed onset, and high mortality. Thus, comprehensive patient assessment and close monitoring are crucial with EGFR-TKI use."

Adverse events • Journal • Retrospective data • Anorexia • Cardiovascular • Heart Failure • Hematological Disorders • Interstitial Lung Disease • Leukopenia • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

Case Report: Grade 4 pneumonitis occurred after thoracic radiotherapy and dacomitinib in a patient with lung adenocarcinoma. (PubMed, Front Oncol) - "Osimertinib combined with chest radiotherapy has a high incidence of pneumonia, dacomitinib is widely used in clinical practice, but there are no studies reporting the pulmonary safety of dacomitinib in combinating with radiotherapy. The concurrent administration of dacomitinib and RT carries the risk of inducing serious pneumonia. This case highlights the potential risk of severe pneumonia associated with this combination therapy, emphasizing the need for further research to clarify its safety and develop effective management strategies."

Journal • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

Targeted treatment and survival in advanced non-squamous non-small cell lung cancer patients - a nationwide and longitudinal study. (PubMed, Front Oncol) - "The median ToT in first line (1L) for EGFR+ patients was 11 months for osimertinib (CI: 10.1-NA) and 9 months (CI: 8.2-11.2) for afatinib, dacomitinib, erlotinib and gefitinib. For ALK+ patients, median ToT in 1L was 20 months (CI: 14.7-23.7for alectinib, 11 months (CI: 4.7-NA) for brigatinib, and 7 months (CI: 2.9-21.6) for crizotinib...ToT for targeted therapies was shorter than progression-free survival in clinical trials. However, patients eligible for targeted therapy still had a survival improvement during the study period."

Journal • Observational data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

In vitro metabolism of targeted covalent inhibitors and their thiol conjugates by gut microbiome from rats, mice, and humans. (PubMed, Drug Metab Dispos) - "In this study, we selected unsubstituted terminal acrylamides (ibrutinib, sotorasib, and divarasib), β-substituted acrylamides (afatinib, neratinib, and dacomitinib), an α-substituted acrylamide (adagrasib), an alkynamide (acalabrutinib), and a salicylaldehyde (voxelotor) to investigate. The species difference information can inform proper preclinical species for better human translation in overall drug behavior. The experimental conditions developed from this work can also be adapted to study gut microbiome metabolism in general across different species."

Journal • Preclinical

Comparative study of degree, neighborhood and reverse degree based indices for drugs used in lung cancer treatment through QSPR analysis. (PubMed, Sci Rep) - "This study focuses on the selection of drugs used to treat lung cancer, including dacomitinib, selpercatinib, tepotinib, trametinib, sotorasib, etoposide, alectinib, paclitaxel, dabrafenib, entrectinib, crizotinib, ceritinib, lorlatinib, afatinib, pralsetinib, brigatinib, erlotinib, adagrasib, gefitinib, vinorelbine, gemcitabine, docetaxel, and pemetrexed. Using molecular structural measures such as degree, neighborhood degree sum, and modified reverse degree, we have developed QSPR models to predict physicochemical properties through the topological indices derived from these structural measures. We then conducted a comparative analysis, incorporating correlation analysis, to identify the model with the highest predictive accuracy."

Clinical • Journal • Lung Cancer • Oncology • Solid Tumor

Real-World Study Shows Efficacy, Safety of First-Line Dacomitinib in Patients With EGFR-Mutated NSCLC (Pharmacy Times) - "At the median follow-up duration of 16.9 months, patients receiving dacomitinib achieved a median PFS of 16.7 months (95% CI, 14.4-25.2). Depending on the type of EGFR mutation, patients with exon 19 deletion achieved a median PFS of 18.1 months (95% CI, 14.5-NE), compared with a median PFS of 15.9 months (95% CI, 12.5-NE) in patients with the L858R mutation. The safety profile was favorable, with 7.2% of patients experiencing adverse events of grade 3 or higher. Initially given at 45 mg, 85.6% of patients required a dose reduction, resulting in a final dosage of 30 mg in 49.0% of cases and 15 mg in 36.6% of cases."

Real-world evidence • Non Small Cell Lung Cancer

PLATFORM Study of Precision Medicine for Rare Tumors (clinicaltrials.gov) - P2 | N=770 | Recruiting | Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2023 ➔ Jul 2028 | Trial primary completion date: Jul 2022 ➔ Jul 2026

Enrollment open • Trial completion date • Trial primary completion date • Oncology • ALK • BRAF • BRCA1 • BRCA2 • CDKN2A • EGFR • HER-2 • KIT • MET • ROS1

A Study to Learn About Dacomitnib in Patients With Non-small Cell Lung Cancer Which Has Spread to the Brain. (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: Pfizer | N=100 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Real-world data of dacomitinib as first-line treatment for patients with EGFR-mutant non-small-cell lung cancer. (PubMed, Sci Rep) - "Dacomitinib demonstrated superior survival benefit compared to gefitinib as a first-line treatment in non-small cell lung cancer (NSCLC) patients with common EGFR mutations through ARCHER 1050. The survival benefit of dacomitinib has been demonstrated, indicating its promising efficacy in a real-world setting. The detection rate of the T790M mutation after dacomitinib treatment failure was comparable to that of other second-generation EGFR-TKIs."

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

Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2025 ➔ Jan 2026 | Trial primary completion date: Jan 2025 ➔ Jan 2026

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

Response to EGFR/NTRK/MET Co-Inhibition Guided by Paired NGS in Advanced NSCLC With Acquired EGFR L858R/T790M/C797S Mutations. (PubMed, J Natl Compr Canc Netw) - "After receiving dacomitinib and almonertinib sequentially, plasma-based NGS revealed the emergence of EGFR T790M-trans-C797S mutations, prompting a switch to a combination therapy of almonertinib and gefitinib...Larotrectinib was incorporated into the dual EGFR-TKI regimen, forming a triplet therapy...This is the first reported case of a novel, targetable POT1::NTRK3 fusion as a potential off-target mechanism mediating EGFR-TKI resistance, occurring alongside MET amplification in a patient with NSCLC harboring acquired EGFR L858R/T790M/C797S mutations. Concomitant inhibition of EGFR, NTRK, and MET was safe and resulted in a significant response, underscoring the importance of precision medicine guided by matched NGS."

Journal • Next-generation sequencing • Dermatitis • Dermatology • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • NTRK • NTRK1 • NTRK3 • POT1

The European Pricing Landscape for Targeted Therapies in Advanced or Metastatic Non-Small Cell Lung Cancer to Achieve Maximum Progression Free Survival (ISPOR-EU 2024) - "Annual costs ranged from selpercatinib UK = €131.406/year and DE = €159.923/year to dacomitinib UK = €37.948/year and capmatinib = €57.063/year. Selpercatinib [24.9 (19.3, NE)] and brigatinib [24.0 (18.5, 43.2)] had the highest mPFS and lorlatinib [6.9 (5.4, 8.2)] and sotorasib [6.8 (5.1, 8.2)] had the lowest mPFS. The study shows that variations exist in total drug costs required to achieving maximum PFS, annual drug prices, and PFS for targeted therapies treating mNSCLC across the UK and Germany."

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