^
    2d
    Multidisciplinary Treatment of Stage III ALK+ NSCLC With Neoadjuvant Alectinib and Chemotherapy (clinicaltrials.gov)
    P2, N=50, Not yet recruiting, Wen-zhao ZHONG
    New P2 trial
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK fusion
    |
    Alecensa (alectinib) • Piqray (alpelisib)
    3d
    Individualized duration of adjuvant alectinib therapy and rechallenge efficacy in ALK-positive non-small cell lung cancer: a case report. (PubMed, Front Med (Lausanne))
    Further research is needed to validate these approaches in larger cohorts. Furthermore, the favorable response to alectinib rechallenge observed in this case suggests that rechallenge therapy may offer a potential value in managing post-adjuvant recurrence, which warrants further investigation.
    Journal
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK positive • ALK rearrangement
    |
    Alecensa (alectinib)
    3d
    A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P3, N=68, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Dec 2026 --> Jun 2030
    Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK positive • ALK fusion • ROS1 fusion • ROS1 positive
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
    |
    Imfinzi (durvalumab) • Rozlytrek (entrectinib) • Alecensa (alectinib)
    4d
    ALINA: A Study Comparing Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With ALK Positive Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P3, N=257, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2026 --> Nov 2031
    Trial completion date
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK positive
    |
    cisplatin • carboplatin • gemcitabine • Alecensa (alectinib) • pemetrexed • vinorelbine tartrate
    5d
    DARWIN II: Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity (clinicaltrials.gov)
    P2, N=50, Completed, University College, London | Active, not recruiting --> Completed | Trial completion date: May 2026 --> Nov 2025 | Trial primary completion date: May 2026 --> Nov 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene)
    |
    HER-2 amplification • BRAF V600 • RET fusion • ALK fusion
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • carboplatin • Alecensa (alectinib) • Kadcyla (ado-trastuzumab emtansine)
    6d
    BO43249: A Study to see How Well and How Safely Different Treatments Work in a Group of Patients with Non-Small Cell Lung Cancer, Chosen Based on their Biomarker Status (2024-511239-91-00)
    P1/2, N=54, Recruiting, F. Hoffmann-La Roche AG | Phase classification: P2/3 --> P1/2
    Phase classification
    |
    ALK fusion
    |
    cisplatin • carboplatin • Alecensa (alectinib) • pemetrexed
    8d
    Treatment of Truncated ALK-positive Bone Cancer Using Crizotinib (Xalkori) or Alectinib (Alecensa) (clinicaltrials.gov)
    P1/2, N=10, Not yet recruiting, China Medical University Hospital
    New P1/2 trial
    |
    ALK (Anaplastic lymphoma kinase)
    |
    Xalkori (crizotinib) • Alecensa (alectinib)
    10d
    Gilteritinib overcomes second‑generation TKIs resistance in ALK‑rearranged non‑small‑cell lung cancer by inhibiting PD‑L1 and CD8 co‑expression. (PubMed, Int J Mol Med)
    Co‑culture and rescue experiments suggested the mechanism involved inhibiting PD‑L1 and CD8 co‑expression, corroborated by animal experiments. Gilteritinib can overcome alectinib resistance and inhibit PD‑L1 and CD8 co‑expression in ALK‑rearranged NSCLC, providing a new therapeutic strategy.
    Journal
    |
    PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • CD8 (cluster of differentiation 8)
    |
    PD-L1 expression • ALK rearrangement
    |
    Alecensa (alectinib) • Xospata (gilteritinib)
    13d
    Cost-effectiveness analysis of lorlatinib as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer in Italy. (PubMed, J Med Econ)
    Probabilistic sensitivity analysis showed an almost 98,40% probability of cost-effectiveness at Italian willingness-to-pay thresholds. From both NHS and societal perspectives, lorlatinib represents a cost-saving and clinically superior first-line treatment option compared with alectinib for patients with ALK-positive advanced NSCLC in Italy.
    Journal • HEOR • Cost-effectiveness
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK positive
    |
    Alecensa (alectinib) • Lorbrena (lorlatinib)
    16d
    MegaMOST: A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors. (clinicaltrials.gov)
    P2, N=455, Recruiting, Centre Leon Berard | Trial completion date: Nov 2026 --> Oct 2027 | Trial primary completion date: Feb 2026 --> Oct 2026
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FLT3 (Fms-related tyrosine kinase 3) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • AXL (AXL Receptor Tyrosine Kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SMAD4 (SMAD family member 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • FLT1 (Fms-related tyrosine kinase 1) • CDK6 (Cyclin-dependent kinase 6) • CCND3 (Cyclin D3) • TYRO3 (TYRO3 Protein Tyrosine Kinase) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF mutation • NRAS mutation • BRAF V600 • KIT mutation • CDKN2A deletion • HRAS mutation • KRAS G12 • PDGFRA mutation • KRAS amplification • NRAS G12
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • Alecensa (alectinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Kisqali (ribociclib) • Ayvakit (avapritinib) • siremadlin (HDM201)
    16d
    A structure-based virtual screening approach to identify novel anaplastic lymphoma kinase inhibitors. (PubMed, J Mol Model)
    Although FDA (Food and Drug Administration) approved inhibitors such as crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib have improved clinical outcomes, their efficacy is often challenged by resistance mechanisms, including secondary kinase domain mutations and activation of bypass pathways. Binding free energies and per-residue contributions were computed using MMGBSA. Boltz-2 machine learning platform to predict KD values and the top three hits were validated using PCA and free energy landscape.
    Journal
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK positive
    |
    Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
    17d
    NRG-LU003: Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=10, Terminated, National Cancer Institute (NCI) | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated; Inadequate accrual rate
    Trial completion date • Trial termination
    |
    ALK positive • ALK rearrangement
    |
    cisplatin • Xalkori (crizotinib) • carboplatin • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • pemetrexed • Alunbrig (brigatinib) • Ensacove (ensartinib)