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    BIOMARKER:

    ALK wild-type

    i
    Other names: NBLST3, CD246, Anaplastic Lymphoma Kinase, Anaplastic Lymphoma Kinase (Ki-1), CD246 Antigen, Mutant Anaplastic Lymphoma Kinase, ALK, ALK Receptor Tyrosine Kinase, Anaplastic Lymphoma Receptor Tyrosine Kinase, ALK Tyrosine Kinase Receptor
    Entrez ID:
    238
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    5d
    A Randomized, Placebo Controlled Study to Evaluate the Safety and Potential Efficacy of MS-20 in Combination with Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer (clinicaltrials.gov)
    P=N/A, N=15, Completed, Microbio Co Ltd | Recruiting --> Completed | Phase classification: P2 --> PN/A | N=30 --> 15 | Trial completion date: Jun 2024 --> Nov 2024 | Trial primary completion date: Jun 2023 --> Oct 2024
    Trial completion • Phase classification • Enrollment change • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK wild-type
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
    |
    Keytruda (pembrolizumab)
    21d
    Clinical Outcomes of Maintenance Durvalumab After Definitive Concurrent Chemoradiotherapy in Unresectable Locally Advanced Stage III NSCLC According to EGFR and ALK Status: Korean Cancer Study Group LU-22-18. (PubMed, JTO Clin Res Rep)
    Significant differences occurred in PFS on the basis of PD-L1 expression with values of 13.6 (95% CI: 10.5-NA), 18.7 (95% CI: 15.1-26.9), and 24.7 (95% CI: 20.7-NA) months for TPS of 0, 1-49, and 50 or higher, respectively (p = 0.02). Durvalumab maintenance therapy after definitive CCRT in unresectable locally advanced NSCLC patients with EGFR or ALK mutation demonstrates comparable clinical outcomes to those with wild-type EGFR/ALK when PD-L1 expression is present.
    Clinical data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • EGFR mutation • EGFR expression • EGFR wild-type • ALK wild-type • ALK translocation
    |
    Imfinzi (durvalumab)
    26d
    ZWI-ZW25-101: Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers (clinicaltrials.gov)
    P1, N=279, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    HER-2 positive • HER-2 overexpression • EGFR wild-type • KRAS wild-type • ALK wild-type • RAS wild-type • ALK-ROS1 fusion • HER-2 positive + HER-2 overexpression • HER-2 positive + RAS wild-type
    |
    paclitaxel • capecitabine • Tukysa (tucatinib) • vinorelbine tartrate • Ziihera (zanidatamab-hrii)
    1m
    Predictive and prognostic factors in patients with Anaplastic Lymphoma Kinase: rearranged early-stage lung adenocarcinoma. (PubMed, Eur J Cardiothorac Surg)
    Clinical T1-2 N0 ALK-rearranged lung adenocarcinoma is an aggressive disease with a specific tropism for lymph nodes and the brain. High-grade tumors are predictive of nodal upstaging. Adjuvant treatment significantly improves DFS and OS in upstaged patients, highlighting the need for personalized preoperative staging and post-surgical management in this cohort.
    Journal
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK rearrangement • ALK wild-type
    1m
    Assessment of BRAF Fusions in 177,227 Thyroid Nodules by Exome-Enriched RNASeq Testing (AMP 2024)
    The detection of BRAF fusions and their many partners was enabled by the Afirma XA exome-enriched RNASeq panel. Although BRAF fusions occurred in only 0.2% of thyroid nodules, they were GSC-Suspicious and lacked typical BRAF/RAS mutations. Interestingly, expression signatures associated with malignancy varied by fusion partner.
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • AGK (Acylglycerol Kinase) • NTRK (Neurotrophic receptor tyrosine kinase) • EXOC4 (Exocyst Complex Component 4) • TRIM24 (Tripartite Motif Containing 24)
    |
    BRAF V600E • BRAF V600 • RAS mutation • ALK wild-type • BRAF fusion • BRAF K601E • BRAF K601
    |
    Afirma® Genomic Sequencing Classifier
    2ms
    Tremelimumab and durvalumab with chemotherapy in first-line treatment for metastatic non-small cell lung cancer: a US-based cost-effectiveness analysis. (PubMed, Transl Lung Cancer Res)
    Scenario analysis confirmed the study's primary findings, with the exception of a scenario where durvalumab was offered at no cost. The findings suggests that T + D + CT may not be a cost-effectiveness first-line treatment for EGFR/ALK wild-type mNSCLC in the US, given its high ICERs and limited cost-effectiveness in the majority of PD-L1 expression subgroups.
    Journal • HEOR • PD(L)-1 Biomarker • IO biomarker • Cost-effectiveness • Cost effectiveness • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • EGFR wild-type • ALK wild-type
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab-actl)
    2ms
    SI-B001 Combined With Chemotherapy in the Treatment of EGFR/ALK WT Recurrent or Metastatic NSCLC. (clinicaltrials.gov)
    P2, N=60, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Aug 2024 --> Jun 2025 | Trial primary completion date: Aug 2024 --> Jun 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type • EGFR wild-type + ALK wild-type
    |
    cisplatin • paclitaxel • docetaxel • pemetrexed • izalontamab (SI-B001)
    2ms
    Durvalumab (D) ± Tremelimumab (T) + Chemotherapy (CT) in the First-Line Treatment of Metastatic (m) NSCLC: 5-Year Survival Data (OS) Update of the POSEIDON Study (DGHO 2024)
    Updated analyses from POSEIDON after median FU of >5 y showed durable long-term OS benefit with the approved regimen of T+D+CT (vs CT alone). These results support its use as a 1L treatment option for pts with mNSCLC, including harder-to-treat subgroups such as those with PD-L1 TC <1%.
    Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    PD-L1 expression • KRAS mutation • EGFR wild-type • STK11 mutation • ALK wild-type • KEAP1 mutation
    |
    VENTANA PD-L1 (SP263) Assay
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab-actl)
    3ms
    Multi-omics dissection of smoking history on clinical outcomes of immunotherapy in advanced non-small cell lung cancer (SITC 2024)
    In PD-L1 TPS ≥50% EGFR/ALK wild-type patients, only patients who have never smoked benefited from first-line Chemo-IO over IO-alone, suggesting IO-alone may be preferable for patients with smoking history to spare chemotherapy toxicity. Tobacco-related mutational signature may potentially reduce stigma, improve patient stratification, and guide more precise IO-based treatment in patients with NSCLC.
    Clinical • Clinical data • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • CDCP1 (CUB Domain Containing Protein 1)
    |
    EGFR mutation • EGFR wild-type • ALK mutation • ALK wild-type
    |
    OncoPanel™ Assay
    3ms
    Induction Chemo-Nivo in Unresectable Stage III NSCLC (clinicaltrials.gov)
    P2, N=1, Terminated, Ralph G Zinner | N=37 --> 1 | Trial completion date: Aug 2027 --> Jul 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Jul 2024; Slow accrual
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Surgery
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK wild-type • ROS1 wild-type
    |
    Opdivo (nivolumab) • paclitaxel • docetaxel
    3ms
    Proteogenomic characterization identifies clinical subgroups in EGFR and ALK wild-type never-smoker lung adenocarcinoma. (PubMed, Exp Mol Med)
    Upregulated cytokines, such as CCL5 and CXCL13, in the immune subgroup may serve as potential targets for combination immunotherapy. Our comprehensive proteogenomic analysis revealed the molecular subtypes of EGFR- and ALK-wild-type NSLA with significant unmet clinical needs.
    Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • CXCL13 (Chemokine (C-X-C motif) ligand 13)
    |
    EGFR wild-type • ALK wild-type • EGFR wild-type + ALK wild-type
    3ms
    SILK BM: A Trial Evaluating Stereotactic Radiotherapy Plus Durvalumab Continuation for Patients With NSCLC Metachronous Oligometastatic Disease Under Durvalumab Consolidation Following Chemoradiation (clinicaltrials.gov)
    P2, N=4, Completed, Institut Claudius Regaud | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Aug 2024 | Trial primary completion date: Dec 2025 --> Aug 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
    |
    EGFR wild-type • ALK wild-type • EGFR wild-type + ALK wild-type
    |
    Imfinzi (durvalumab)
    4ms
    Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes from the Phase 3 POSEIDON Trial. (PubMed, J Thorac Oncol)
    After median follow-up of >5 years, T+D+CT showed durable long-term OS benefit versus CT, supporting its use as first-line treatment in mNSCLC, including in patient subgroups with harder-to-treat disease.
    P3 data • Journal • Combination therapy • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    PD-L1 expression • KRAS mutation • EGFR wild-type • STK11 mutation • ALK wild-type • KEAP1 mutation
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab-actl)
    8ms
    Tiragolumab With Atezolizumab Plus Bevacizumab in Previously-Treated Advanced Non-squamous NSCLC (clinicaltrials.gov)
    P2, N=42, Recruiting, Georgetown University | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    PD-L1 expression • ALK wild-type • ROS1 wild-type
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • tiragolumab (RG6058)
    8ms
    Phase II Anti-PD1 Epigenetic Therapy Study in NSCLC. (clinicaltrials.gov)
    P2, N=143, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=101 --> 143
    Enrollment change • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • EGFR exon 19 deletion • ALK positive • ALK rearrangement • EGFR wild-type • ALK wild-type • ALK translocation
    |
    Opdivo (nivolumab) • Jingzhuda (entinostat) • Onureg (azacitidine oral)
    9ms
    AK105-301: A Study of Anti-PD-1 AK105 in Patients With Metastatic Nonsquamous Non-small Cell Lung Cancer (clinicaltrials.gov)
    P3, N=164, Terminated, Akeso | Trial completion date: Jun 2024 --> Dec 2023 | Active, not recruiting --> Terminated; corporate strategy adjustment
    Trial completion date • Trial termination • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR wild-type • ALK wild-type • EGFR wild-type + ALK wild-type
    |
    carboplatin • Focus V (anlotinib) • pemetrexed • Anniko (penpulimab)
    10ms
    Study to Assess Neoadjuvant Durvalumab (D) and Platinum-Based Chemotherapy (CT), Followed by Either Surgery and Adjuvant D or CRT and Consolidation D, in Resectable or Borderline Resectable Stage IIB-IIIB NSCLC (MDT-BRIDGE) (clinicaltrials.gov)
    P2, N=140, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting | Trial primary completion date: Mar 2027 --> Apr 2026
    Enrollment open • Trial primary completion date • Surgery
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR wild-type • ALK wild-type • EGFR wild-type + ALK wild-type
    |
    Imfinzi (durvalumab)
    10ms
    The association of genomic alterations with PD-L1 expression in Chinese patients with EGFR/ALK wild-type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy. (PubMed, Cancer Med)
    This study offers insights into genomic features of Chinese EGFR/ALK wild-type lung adenocarcinoma patients based on PD-L1 expression. Notably, Hippo pathway alterations were linked to improved immunotherapy outcomes. These findings suggest connections between the Hippo pathway and PD-L1 expression, warranting further clinical and functional investigations. The research advances our understanding of PD-L1 expression's genomic context and immunotherapy response in EGFR/ALK wild-type lung adenocarcinoma.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD68 (CD68 Molecule)
    |
    PD-L1 expression • TMB-H • EGFR expression • EGFR wild-type • ALK wild-type
    10ms
    PACIFIC-8: A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC (clinicaltrials.gov)
    P3, N=860, Recruiting, AstraZeneca | Trial completion date: Sep 2029 --> Aug 2030 | Trial primary completion date: Jun 2027 --> Jun 2028
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)
    |
    EGFR wild-type • ALK wild-type • EGFR wild-type + ALK wild-type
    |
    Imfinzi (durvalumab) • domvanalimab (AB154)
    10ms
    SI-B001 Combined With Chemotherapy in the Treatment of EGFR/ALK WT Recurrent or Metastatic NSCLC. (clinicaltrials.gov)
    P2, N=60, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Dec 2023 --> Apr 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type • EGFR wild-type + ALK wild-type
    |
    cisplatin • paclitaxel • docetaxel • pemetrexed • izalontamab (SI-B001)
    10ms
    Cumulative incidence and risk factors of brain metastases in metastatic non-small cell lung cancer without baseline brain metastasis: Pooled analysis of individualized patient data from IMpower130, IMpower131, and IMpower150. (PubMed, Cancer)
    In patients with metastatic EGFR/ALK wild-type NSCLC without baseline BMs, adding atezolizumab in the first-line treatment might not reduce the CI-BM. However, the administration of bevacizumab may reduce the risk of BMs.
    Retrospective data • Journal • PD(L)-1 Biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK mutation • ALK wild-type
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab)
    11ms
    LOTOS: A Study to Investigate Efficacy and Safety of Ceralasertib Plus Durvalumab in Participants Aged ≥ 18 Years With Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Progressed on or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy (clinicaltrials.gov)
    P2, N=39, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)
    11ms
    BMC128-001: A First-in-human (FIH) Combination Treatment Study With a Single Dose Level of BMC128 (clinicaltrials.gov)
    P1, N=12, Active, not recruiting, Biomica Ltd. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR wild-type • ALK wild-type
    |
    Opdivo (nivolumab) • BMC128
    1year
    Olaparib maintenance versus placebo in platinum-sensitive non-small cell lung cancer: the Phase 2 randomized PIPSeN trial. (PubMed, Br J Cancer)
    PIPSeN was terminated early after enrollment of only 50% of the pre-planned population, thus being statistically underpowered. Olaparib maintenance did neither improve median PFS nor OS in this patient population.
    P2 data • Journal • PARP Biomarker
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    ALK wild-type
    |
    Lynparza (olaparib)
    1year
    The association of chest computed tomography-defined visual emphysema and prognosis in patients with nonsmall cell lung cancer. (PubMed, ERJ Open Res)
    CT-defined emphysema, especially CLE with LAA%>17%, is an independent predictor of NSCLC prognosis. Moreover, prospective studies are needed to further explore this association.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type
    1year
    Induction Chemo-Nivo in Unresectable Stage III NSCLC (clinicaltrials.gov)
    P2, N=37, Recruiting, Ralph G Zinner | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Surgery
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK wild-type • ROS1 wild-type
    |
    Opdivo (nivolumab) • paclitaxel • docetaxel
    1year
    Study to Assess Neoadjuvant Durvalumab (D) and Platinum-Based Chemotherapy (CT), Followed by Either Surgery and Adjuvant D or CRT and Consolidation D, in Resectable or Borderline Resectable Stage IIB-IIIB NSCLC (MDT-BRIDGE) (clinicaltrials.gov)
    P2, N=140, Not yet recruiting, AstraZeneca | Trial completion date: Apr 2027 --> Sep 2027 | Trial primary completion date: Apr 2026 --> Mar 2027
    Trial completion date • Trial primary completion date • Surgery
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR wild-type • ALK wild-type • EGFR wild-type + ALK wild-type
    |
    Imfinzi (durvalumab)
    1year
    Durvalumab (D) ± tremelimumab (T) + chemotherapy (CT) in first-line metastatic (m) NSCLC: 5-year overall survival (OS) update from the POSEIDON study (ESMO-IO 2023)
    Conclusions Updated analyses from POSEIDON after median FU of >5 y showed durable long-term OS benefit with the approved regimen of T+D+CT (vs CT alone). These results support its use as a 1L treatment option for pts with mNSCLC, including harder-to-treat subgroups such as those with PD-L1 TC <1%.
    Late-breaking abstract • Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    PD-L1 expression • KRAS mutation • EGFR wild-type • STK11 mutation • ALK wild-type • KEAP1 mutation
    |
    VENTANA PD-L1 (SP263) Assay
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab-actl)
    1year
    Comprehensive genomic and immune profiling of ALK fusion-positive and negative lung adenocarcinomas (SITC 2023)
    Our results show that ALK rearrangements are associated with elevated levels of PD-L1 tumore expression. These findings support consideration for including patients with ALK+ LAs in appropriate clinical trials.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • PD-1 (Programmed cell death 1)
    |
    PD-L1 expression • ALK positive • ALK rearrangement • ALK fusion • ALK wild-type
    |
    PD-L1 IHC 22C3 pharmDx
    1year
    Avelumab vs platinum-based doublet chemotherapy as first-line treatment for patients with high-expression PD-L1+ metastatic non-small cell lung cancer: primary analysis from the phase 3 JAVELIN Lung 100 trial. (PubMed, J Thorac Oncol)
    P3; Longer median OS and PFS were observed with avelumab vs platinum-based doublet chemotherapy in advanced NSCLC, but differences in OS and PFS were not statistically significant, and the trial did not meet its primary objective.
    Journal • P3 data • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type
    |
    PD-L1 IHC 73-10 pharmDx
    |
    Bavencio (avelumab)
    over1year
    Induction Chemo-Nivo in Unresectable Stage III NSCLC (clinicaltrials.gov)
    P2, N=37, Not yet recruiting, Ralph G Zinner
    New P2 trial • Combination therapy • Surgery
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK wild-type • ROS1 wild-type
    |
    Opdivo (nivolumab) • paclitaxel • docetaxel
    over1year
    A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma (clinicaltrials.gov)
    P3, N=584, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • HER-2 amplification • BRAF V600 • KRAS G12D • EGFR wild-type • KRAS G12V • RET mutation • ALK wild-type • ROS1 fusion • ROS1 rearrangement • MET mutation • RET rearrangement • KRAS G12 • EGFR wild-type + ALK wild-type • KRAS amplification • NTRK fusion
    |
    docetaxel • izalontamab (SI-B001)
    over1year
    ZWI-ZW25-101: Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers (clinicaltrials.gov)
    P1, N=279, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Aug 2023 --> Jul 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    HER-2 positive • HER-2 overexpression • EGFR wild-type • KRAS wild-type • ALK wild-type • RAS wild-type • EGFR wild-type + ALK wild-type • ALK-ROS1 fusion
    |
    paclitaxel • capecitabine • Tukysa (tucatinib) • vinorelbine tartrate • Ziihera (zanidatamab-hrii)
    over1year
    Genetic Predictors of Benefit to Pembrolizumab (clinicaltrials.gov)
    P2, N=19, Terminated, Columbia University | Active, not recruiting --> Terminated; Frontline pembrolizumab approved in NSCLC as monotherapy and in combination with chemotherapy representing a new standard of care.
    Trial termination • Combination therapy • Tumor mutational burden • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase)
    |
    KRAS mutation • EGFR mutation • EGFR wild-type • KRAS wild-type • RAS mutation • ALK wild-type
    |
    Keytruda (pembrolizumab) • carboplatin • albumin-bound paclitaxel • pemetrexed
    over1year
    Durvalumab ± Tremelimumab + Chemotherapy in 1L Metastatic NSCLC: Characterisation of patients with PFS ≥12 months in POSEIDON (IASLC-WCLC 2023)
    In POSEIDON, more than twice as many patients derived long-term clinical benefit (PFS 12 months) when treated with T+D+CT versus CT alone (16.6% vs 6.8%).
    Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • EGFR wild-type • ALK wild-type
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab-actl)
    over1year
    The Safety and Efficacy of Induction Chemoimmunotherapy Followed by Radiotherapy and Consolidation Immunotherapy in Locally Advanced NSCLC (IASLC-WCLC 2023)
    Patients received 3 cycles of carboplatin, paclitaxel (squamous NSCLC) or pemetrexed (non-squamous NSCLC), and tislelizumab, followed by standard thoracic radiotherapy. The findings of this study suggest promising antitumor activity and manageable safety of induction chemoimmunotherapy followed by radiotherapy and consolidation immunotherapy in patients with locally advanced NSCLC.
    Clinical • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type
    |
    carboplatin • paclitaxel • Tevimbra (tislelizumab-jsgr) • pemetrexed
    over1year
    LIPI-based Score Predicting OS Benefit for the Addition of Chemotherapy to Pembrolizumab in aNSCLC with PD-L1 TPS≥50% (IASLC-WCLC 2023)
    With the limitations of the retrospective analysis, the proposed LIPI-based score seems to predict OS with P and PCT. Prospective validation is required.
    PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    LDH elevation • ALK wild-type • ROS1 wild-type
    |
    Keytruda (pembrolizumab)
    over1year
    Real World Outcomes after Chemotherapy and Immunotherapy in Patients with Metastatic Non-Small Cell Lung Cancer in Europe (IASLC-WCLC 2023)
    In this European cohort of patients with mNSCLC having disease progression on anti-PD-1/anti-PD-L1 and PDC, treatment regimens were heterogenous and predominantly included non-platinum chemotherapies. Poor clinical outcomes demonstrate an unmet clinical need that warrant more efficacious therapies for anti-PD-1/anti-PD-L1 and PDC-refractory patients.
    Clinical • Real-world evidence • Real-world • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR wild-type • ALK wild-type • ROS1 fusion • ALK-ROS1 fusion
    over1year
    Three-Year Outcomes with First-Line Pembrolizumab, in Patients with Non-Small-Cell Lung Cancer and A PD-L1 Tumor Proportion Score >90% (IASLC-WCLC 2023)
    Pembrolizumab monotherapy continues to demonstrate a meaningful long-term survival benefit in patients with advanced NSCLC and a PD-L1 TPS ≥90%. NSCLCs with very high PD-L1 TPS may have a more favorable genomic and immunophenotypic profile. These findings have important implications for treatment selection and clinical trial interpretation and design.
    Clinical • Tumor mutational burden • Tumor proportion score • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C) • FOXP3 (Forkhead Box P3)
    |
    PD-L1 expression • PD-L1 overexpression • HER-2 mutation • EGFR wild-type • STK11 mutation • ALK wild-type • SMARCA4 mutation
    |
    Keytruda (pembrolizumab)
    over1year
    A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma (clinicaltrials.gov)
    P3, N=584, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.
    New P3 trial
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • HER-2 amplification • BRAF V600 • KRAS G12D • EGFR wild-type • KRAS G12V • RET mutation • ALK wild-type • ROS1 fusion • ROS1 rearrangement • MET mutation • RET rearrangement • KRAS G12 • EGFR wild-type + ALK wild-type • KRAS amplification • NTRK fusion
    |
    docetaxel • izalontamab (SI-B001)
    over1year
    LOTOS: A Study to Investigate Efficacy and Safety of Ceralasertib Plus Durvalumab in Participants Aged ≥ 18 Years With Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Progressed on or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy (clinicaltrials.gov)
    P2, N=38, Recruiting, AstraZeneca
    New P2 trial • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR wild-type • ALK wild-type
    |
    Imfinzi (durvalumab) • ceralasertib (AZD6738)