our Premium Content: News alerts, weekly reports and conference planners

GENE:

ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

News alerts, weekly reports and conference planners

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

1 day ago

Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

Structures and pH-dependent dimerization of the sevenless receptor tyrosine kinase. (PubMed, Mol Cell)

We use cryo-electron microscopy and biophysical methods to determine the structural basis of ligand binding and pH-dependent dimerization of Sev, and we discuss the implications in the process of Sev activation. The Sev human homolog, receptor oncogene from sarcoma 1 (ROS1), is associated with oncogenic transformations, and we discuss their structural similarities.

2 days ago

Journal

ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

Real-world treatment patterns, biomarker testing, and clinical outcomes of metastatic non-small cell lung cancer patients in the immunotherapy era. (PubMed, Front Oncol)

For ECOG PS 0-1 and PD-L1 <50% patients, median rwOS was 14.3 (95% CI: 10.1-NR) and 11.2 (95% CI: 9.1-21.3) months for PDC and PBC, respectively. Our real-world data support the benefit of single-agent PD-1 inhibitor monotherapy for patients with PD-L1 high expression or PD-1 inhibitor combination for all patients diagnosed with mNSCLC with no known EGFR/ALK/ROS1 aberrations, initiating 1L treatment.

2 days ago

Clinical data • Journal • HEOR • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Biomarker testings • Real-world • Metastases

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

PD-L1 expression • PD-L1 overexpression

Case Series: EGFR and ROS-1 Co-Occurrence in Advanced Non-Small Cell Lung Cancer. (PubMed, J Immunother Precis Oncol)

The first case was treated with osimertinib, and currently has had a stable disease on this medication for more than 3 years...There are many other unanswered questions, such as the best treatment sequencing or even the combined targeted therapy approach. This case series may add some information to the current literature.

3 days ago

Journal • Metastases

EGFR (Epidermal growth factor receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

Tagrisso (osimertinib)

Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)

Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.

5 days ago

Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion

OncoExTra™ test

Comparison of Clinical Sensitivity for Kinase Fusion Detection in Thyroid Carcinoma by Paired Primer Targeted Methods (AMP 2024)

AFP, the targeted, breakpoint/fusion partner agnostic panel, outperformed 3 other established panels using real-world, fusion-driven thyroid cancers by an average detection frequency of 39%. Such findings demonstrate the importance in sequencing panel selection for fusion-driven thyroid cancer detection, and the potential downstream consequences for diagnostic utility and therapeutic intervention.

5 days ago

Clinical

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

NTRK1 fusion • FGFR2 fusion • ALK fusion

FusionPlex® Dx • Illumina Focus Panel • Oncomine Focus Assay

Same-Day Molecular Testing Results from Cytology Specimens: The Next Frontier of the Rapid On-Site Evaluation? (AMP 2024)

It is feasible to yield actionable molecular testing results from cytology specimens within 2 to 3 hours of the patient's diagnostic procedure, and aspirate smears can be triaged for this use at the time of the rapid on-site evaluation. Targetable genetic alterations can be detected from destained cytology aspirate smear slides and unstained FFPE cell blocks with high accuracy, precision, and analytical sensitivity and specificity. The cost of each cartridge ranges from $127 to $462 and is covered by the average national reimbursement schemes.

5 days ago

Cytology

EGFR (Epidermal growth factor receptor) • 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)

ALK rearrangement • RET rearrangement

Idylla™ KRAS Mutation Test

Re-verification and Report Ruling Revision of NTRK Fusion Results of Idylla GeneFusion Assay after Manufacturer Algorithm Update (AMP 2024)

Our standard operating procedure (SOP) was updated to perform orthogonal confirmation testing for stand-alone equivocal NTRK1/2 and equivocal NTRK3 (5' failure), but to ignore equivocal NTRK3 (5' intact) and report as NTRK2/3 indeterminate. Re-verification showed no change to ALK, ROS1, RET, MET ex14, and NTRK1 results. Sensitivity of NTRK2 detection was significantly increased (80% after orthogonal testing).

5 days ago

ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • NTRK fusion

Idylla™ GeneFusion Assay

Characterization of ESR1-CCDC170 and Other Intra-Chromosomal Gene Fusions in FFPE Samples with Oncomine Precision Assay on Ion Torrent GeneXus System (AMP 2024)

This report offers a thorough characterization of expected prevalence and expression levels for CSFs and NDFs with an NGS study of a broad scope. We describe ESR1 fusions in a cohort of thousands of breast tumors and show lower median expression levels relative to NDFs such as ALK, ROS1, and RET fusions. Our findings suggest that some CSFs, like ESR1 fusions in breast cancer, may be the result of tandem duplication with upstream partners, and may be subclonal and acquired later in cancer progression.

5 days ago

ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • CCDC170(Coiled-Coil Domain Containing 170) • RSPO3 (R-Spondin 3)

RET fusion • MET exon 14 mutation • ROS1 fusion • FGFR3 fusion • ER-CCDC170 fusion

Oncomine Precision Assay

Rapid On-Site Next-Generation Sequencing (NGS) Testing as an Alternative to Single Gene or Send-Out Molecular Testing in Lung and Colon Cancers (AMP 2024)

Given the importance of timely, comprehensive molecular test results to inform appropriate treatment decisions in NSCLC and CRC, these results suggest that the rapid in-house GeneXus NGS system can reduce TAT with comparable failure rates and alteration detection rates compared to other testing methods. Further studies evaluating the impact of the rapid OPA compared to other methods on patient care, as well as the economics of different molecular tests, are ongoing.

5 days ago

Next-generation sequencing

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) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

KRAS G12C • KRAS G12

Oncomine Precision Assay

Clinical Utility of Circulating Tumor DNA Profiling in Detecting Targetable Fusions in Non-small-Cell Lung Cancer (AMP 2024)

Fusion detection using ctDNA CGP showed high concordance to tissue tests and high accuracy in predicting therapeutic response in NSCLC patients. The ctDNA CGP is expected to provide an important diagnostic option for fusion detection.

5 days ago

Clinical • Circulating tumor DNA

ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

ALK positive • FGFR2 fusion • ALK fusion

TruSight Oncology 500 Assay

The sequence of chemotherapy and anti-PD-1 antibody influence the efficacy of immunochemotherapy for non-oncogene addicted advanced/locally advanced non small cell lung cancer: A prospective, multicenter, open-label, controlled study. (ChiCTR2400090941)

P=N/A, N=135, Not yet recruiting, Affiliated Hospital of Guilin Medical University; Affiliated Hospital of Guilin Medical University

8 days ago

New trial • Metastases

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

BRAF V600E • BRAF V600

Cytokines used for predicting the efficacy of immunotherapy in non-small cell lung cancer (ChiCTR2400089450)

P=N/A, N=100, Completed, Chongqing University Three Gorges Hospital（Chongqing Three Gorges Central Hospital）; Chongqing University Three Gorges Hospital（Chongqing Three

8 days ago

New trial • Predictive model

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

EGFR mutation • ALK mutation • ROS1 fusion

The Effectiveness and Safety of Sintilimab Plus Bevacizumab Combined with Pemetrexed and Platinum-Based Drugs in Retrospective Analysis for Advanced Non-Small Cell Lung Cancer Patients Without Targeted Therapy (ChiCTR2400089107)

P4, N=100, Not yet recruiting, Anhui Chest Hospital; Anhui Chest Hospital

8 days ago

New P4 trial • Metastases

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

ALK fusion • ALK mutation • RET mutation • ROS1 fusion • ROS1 mutation

Avastin (bevacizumab) • Tyvyt (sintilimab) • pemetrexed

A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BGB-C354, an Antibody-Drug Conjugate Targeting B7H3, Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors (ChiCTR2400091198)

P1, N=92, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

8 days ago

New P1 trial • Combination therapy • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD276 (CD276 Molecule) • NTRK (Neurotrophic receptor tyrosine kinase)

EGFR mutation • HER-2 negative • EGFR wild-type • CD276 expression

Tevimbra (tislelizumab-jsgr)

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Profiles, and Preliminary Efficacy of SYS6023 in Patients with Advanced Solid Tumors (ChiCTR2400089836)

P1, N=388, Recruiting, Shanghai Chest Hospital; CSPC Megalith Biopharmaceutical Co., Ltd

8 days ago

New P1 trial • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • HER-2 negative • BRAF V600 • HER-2 expression • ALK positive • MET amplification • ALK fusion • ERBB3 expression • RET mutation • ROS1 fusion • MET mutation • NRG1 fusion • RET rearrangement • KRAS G12 • KRAS amplification • ER expression • PGR expression • ALK-ROS1 fusion • NRG1 fusion • NTRK fusion

10d

ICARUS-LUNG01: Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov)

P2, N=100, Active, not recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Recruiting --> Active, not recruiting | Trial completion date: Nov 2025 --> Mar 2028 | Trial primary completion date: Nov 2022 --> Mar 2025

10 days ago

Enrollment closed • Trial completion date • Trial primary completion date • Metastases

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)

EGFR mutation • BRAF mutation • RET mutation • MET mutation • NTRK fusion

datopotamab deruxtecan (DS-1062a)

11d

Clinical utility of circulating tumor DNA profiling in detecting targetable fusions in non-small cell lung cancer. (PubMed, Front Oncol)

Fusion detection using ctDNA CGP showed high concordance with tissue tests and accuracy in predicting therapeutic responses in patients with non-small cell lung cancer. ctDNA CGP may provide an important diagnostic tool for fusion detection.

11 days ago

Journal • Circulating tumor DNA

ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

ALK positive • FGFR2 fusion • ALK fusion • ROS1 fusion

11d

Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC. (PubMed, JTO Clin Res Rep)

Overall, both existing literature and our data suggest that RET-FISH testing can be used for rapid screening of RET rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm RET-FISH-positive cases is essential for ensuring that only patients likely to benefit from RET-target therapy receive the treatment.

11 days ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

RET rearrangement

11d

Response to platinum-based therapies in second-line after immunotherapy in advanced or metastatic non-small-cell lung cancer PD-L1 ≥50. (PubMed, Transl Lung Cancer Res)

All first-line treatments applied pembrolizumab (median dose: 12 cycles)...Of the patients with PRs or CRs, 75% were treated with platinum plus pemetrexed...The current response to second-line platinum-based therapies for patients with advanced NSCLC after immunotherapy appears to achieve favourable response rates and be an optimal treatment after progression to immunotherapy. Prior immunotherapy appears to enhance these patients' platinum response, though future confirmatory studies are necessary.

11 days ago

Journal • PD(L)-1 Biomarker • IO biomarker • Metastases

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

EGFR mutation • ALK mutation

Keytruda (pembrolizumab) • pemetrexed

11d

The oncogenic Flip in patients with leptomeningeal metastatic disease (LMD): Longitudinal detection in cerebrospinal fluid tumor cells (CSF-TCs) reveals implications for differential treatment of the LMD tumor (SNO 2024)

CNSide can be used to detect oncogene amplification on CSF-TCs of patients with LMD, and mutational status of the LMD tumor may differ from the original tumor biopsy. CSF-TC analysis may provide therapeutic insights that vary from the original tumor and could open the door to additional treatment targets for patients struck with LMD.

11 days ago

Clinical • PD(L)-1 Biomarker • IO biomarker • Tumor cell • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1)

CNSide™ Cerebrospinal Fluid Assay

11d

Fusion transcriptome landscape in Glioblastoma (SNO 2024)

Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.

11 days ago

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)

TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion

MI Tumor Seek™

14d

Actionable Structural Variant Detection via RNA-NGS and DNA-NGS in Patients With Advanced Non-Small Cell Lung Cancer. (PubMed, JAMA Netw Open)

Emerging structural variants (eSVs) were found to have a combined prevalence to be 0.7%, with only 47.5% of eSVs detected by DNA-NGS. In this cohort study, the detection of structural variants via concurrent RNA-NGS and DNA-NGS was higher across multiple NCCN-guideline recommended biomarkers compared with DNA-NGS alone, suggesting that RNA-NGS should be routinely implemented in the care of patients with advanced NSCLC.

14 days ago

Retrospective data • Journal • Next-generation sequencing • Metastases

ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ROS1 fusion

14d

Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer (clinicaltrials.gov)

P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

14 days ago

Trial completion date • Trial primary completion date

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

KRAS G12C • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • ALK rearrangement • EGFR L861Q • ROS1 positive • KRAS G12 • EGFR exon 20 mutation • MET positive • EGFR negative

Opdivo (nivolumab) • gemcitabine • docetaxel • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Cyramza (ramucirumab) • Cometriq (cabozantinib capsule) • ABP 206 (nivolumab biosimilar)

18d

MORAb-202-G000-201: A Study to Evaluate the Safety, Tolerability, and Efficacy of MORAb-202 (Herein Referred to as Farletuzumab Ecteribulin), a Folate Receptor Alpha (FRα)-Targeting Antibody-drug Conjugate (ADC) in Participants With Selected Tumor Types (clinicaltrials.gov)

P1/2, N=142, Recruiting, Eisai Inc. | Trial completion date: Mar 2025 --> Oct 2024 | Trial primary completion date: Mar 2025 --> Oct 2024

18 days ago

Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

HER-2 negative • PGR negative

prednisone • dexamethasone • farletuzumab ecteribulin (MORAb-202) • prednisolone

18d

LUNG-MAP SUB-STUDY: Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has Increased Copies of the MET Gene (An Expanded Lung-MAP Treatment Trial) (clinicaltrials.gov)

P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

18 days ago

Enrollment open • Metastases

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) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • HER-2 mutation • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • RET rearrangement

Rybrevant (amivantamab-vmjw)

19d

CIGB-300 internalizes and impairs viability of NSCLC cells lacking actionable targets by inhibiting casein kinase-2 signaling. (PubMed, Sci Rep)

Finally, intravenous injection of CIGB-300 in a cell line-based xenograft corroborated CIGB-300's anti-tumor effects and suggested concurrent in situ reductions of CSNK2ɑ subunit and downstream RPS6s235/236 phosphorylation. Overall, CIGB-300 therapeutic hypothesis and antineoplastic effects demonstrated herein, further support the evaluation of this clinical-grade CK2 inhibitor in advanced NSCLC with limited therapeutic options.

19 days ago

Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

EGFR mutation • ALK mutation

CIGB-300

19d

Coformulation of Pembrolizumab/Vibostolimab (MK-7684A) Versus Pembrolizumab (MK-3475) Monotherapy for Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Metastatic Non-Small Cell Lung Cancer (MK-7684A-003, KEYVIBE-003) (clinicaltrials.gov)

P3, N=1264, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jun 2028 --> Dec 2026 | Trial primary completion date: Apr 2026 --> Dec 2026

19 days ago

Trial completion date • Trial primary completion date • Metastases

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • PD-1 (Programmed cell death 1)

PD-L1 expression

Keytruda (pembrolizumab) • vibostolimab/pembrolizumab (MK-7684A)

21d

Circulating Tumor DNA Alterations in Non-small Cell Lung Cancer Patients Treated With Pembrolizumab (clinicaltrials.gov)

P=N/A, N=10, Terminated, Columbia University | N=37 --> 10 | Recruiting --> Terminated; Low accrual

21 days ago

Enrollment change • Trial termination

PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

Signatera™

Keytruda (pembrolizumab)

21d

Association of mutation profiles with metastasis in patients with non-small cell lung cancer. (PubMed, Front Oncol)

Patients with ALK mutant, BRAF mutant or NRAS mutant were more prone to metastasis, while the HER 2 mutation group was less metastatic. Patients with EGFR mutant NSCLC are more likely to develop bone, lung, or brain metastasis.

21 days ago

Journal

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) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • ALK mutation • MET mutation • EGFR mutation + PIK3CA mutation

24d

CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways. (PubMed, Diseases)

CDX2-suppressed colorectal cancers constitute a genomically distinct subset of colon and rectal cancers that have a lower prevalence of KRAS, APC, and TP53 mutations, but a high prevalence of mutations in less commonly mutated colorectal cancer genes. These alterations could serve as targets for personalized therapeutics in this subset.

24 days ago

Journal • BRCA Biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • APC (APC Regulator Of WNT Signaling Pathway) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CDX2 (Caudal Type Homeobox 2)

TP53 mutation • KRAS mutation • BRAF mutation • ATM mutation • APC mutation • ERBB3 mutation

25d

REPOSE: REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis (clinicaltrials.gov)

P2, N=20, Not yet recruiting, MedSIR | Initiation date: Aug 2024 --> Nov 2024

25 days ago

Trial initiation date

ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

Augtyro (repotrectinib)

27d

ELEVATELung&UC: Study of Magrolimab in Patients With Solid Tumors (clinicaltrials.gov)

P2, N=106, Terminated, Gilead Sciences | Active, not recruiting --> Terminated; Sponsor decision to terminate study

27 days ago

Trial termination

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)

MET exon 14 mutation

docetaxel • magrolimab (ONO-7913)

29d

Targeted and cytotoxic inhibitors used in the treatment of lung cancers. (PubMed, Pharmacol Res)

On the order of 20% of NSCLCs bear activating mutations in EGFR and are treated with osimertinib and other kinase antagonists...Local treatment options to control thoracic disease include radiotherapy and surgery. In patients with extensive-stage disease, a platinum agent (cisplatin or carboplatin) combined with etoposide and an anti-PDL1 inhibitor (atezolizumab or durvalumab) for four cycles followed by anti-PDL1 maintenance therapy is the recommended first-line regimen.

29 days ago

Review • Journal • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)

EGFR mutation • BRAF mutation • ALK translocation

Mekinist (trametinib) • cisplatin • Tagrisso (osimertinib) • Tecentriq (atezolizumab) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Retevmo (selpercatinib) • pemetrexed • etoposide IV • Tabrecta (capmatinib)

30d

Systemic ALK-Negative Anaplastic Large Cell Lymphoma: Insights into Morphologic, Immunophenotypic, Genetic and Molecular Characteristics. (PubMed, Hum Pathol)

Gene expression profiling data have shownthat ALK-negative ALCL has distinctive molecular signatures, different from ALK+ ALCL and other T-cell lymphomas. Better understanding of the morphologic, immunophenotypic, genetic and molecular features of ALK-negative ALCL will help establish the correct diagnosis, guide therapeutic strategies and improve patient outcomes.

30 days ago

Journal

ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • JAK2 (Janus kinase 2) • TNFRSF8 (TNF Receptor Superfamily Member 8) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • TYK2 (Tyrosine Kinase 2) • TP63 (Tumor protein 63) • DUSP22 (Dual Specificity Phosphatase 22) • USP22 (Ubiquitin Specific Peptidase 22)

ALK positive • ALK rearrangement • TNFRSF8 expression • ALK negative • STAT3 mutation • JAK1 mutation

A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)

P1, N=245, Recruiting, Incyte Corporation | N=165 --> 245

1 month ago

Enrollment change • Metastases

HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PGR (Progesterone receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

HER-2 negative • ER negative • PGR negative

INCA33890

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov)

P1, N=53, Terminated, Pfizer | Trial completion date: Nov 2025 --> Jun 2024 | Active, not recruiting --> Terminated; The study was prematurely discontinued due to strategic reasons, not major safety concerns, futility, or requests from any regulatory authorities

1 month ago

Trial completion date • Trial termination • Combination therapy • Metastases

ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NF1 (Neurofibromin 1)

BRAF V600E • EGFR mutation • BRAF V600 • ALK positive • NF1 mutation • RAS mutation • ROS1 positive

Erbitux (cetuximab) • Lorbrena (lorlatinib) • Mektovi (binimetinib) • Braftovi (encorafenib) • PF-07284892

Repotrectinib: Redefining the therapeutic landscape for patients with ROS1 fusion-driven non-small cell lung cancer. (PubMed, Clin Transl Med)

The FDA-approved tyrosine kinase inhibitors (TKIs) crizotinib and entrectinib have demonstrated efficacy in treating ROS1 fusion-positive NSCLC. These findings underscore the potential of repotrectinib to address unmet needs in ROS1-rearranged NSCLC, offering durable responses and improved intracranial activity. Future research should prioritize developing next-generation, selective ROS1 inhibitors to reduce Trk-mediated toxicities and improve treatment tolerance.

1 month ago

Review • Journal

ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

ROS1 fusion • ROS1 positive • ROS1 rearrangement • ROS1 G2032R

Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)

Crizotinib (Xalkori) Expanded Access Protocol for the Treatment of Adult or Pediatric Patients (clinicaltrialsregister.eu)

P4, N=14, Pfizer, Inc

1 month ago

New P4 trial

ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)

NTRK3 fusion • ALK mutation • ETV6-NTRK3 fusion • ALK translocation

Xalkori (crizotinib)

ASPYRE-Lung: validation of a simple, fast, robust and novel method for multi-variant genomic analysis of actionable NSCLC variants in FFPE tissue. (PubMed, Front Oncol)

The technology is simple and fast, requiring only four reagent transfer steps using standard laboratory equipment (PCR and qPCR instruments) with analysis via a cloud-based algorithm. The ASPYRE-Lung assay has the potential to be transformative in facilitating access to rapid, actionable molecular profiling of tissue for patients with non-small cell carcinoma.

1 month ago

Journal

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) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

MET exon 14 mutation

ASPYRE-Lung

A Study of DSP107 Alone and in Combination with Atezolizumab for Patients with Advanced Solid Tumors (clinicaltrials.gov)

P1/2, N=125, Recruiting, Kahr Medical | Trial completion date: Dec 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

1 month ago

Trial completion date • Trial primary completion date

KRAS mutation • EGFR mutation • BRAF mutation • KRAS wild-type • RET mutation • RAS wild-type

Tecentriq (atezolizumab) • DSP-107

A Phase II Study of Sotorasib (AMG 510) in Participants with Previously Treated Stage IV or Recurrent KRASG12C Mutated Non-Squamous Non-Small Cell Lung Cancer (ECOG-ACRIN Lung-MAP Sub-Study) (SWOG-Fall 2024)

Ten additional participants have experienced Grade 4 treatment-related adverse events, nine of which are non-hematologic toxicities. There is one participant with a Grade 3 treatment-related Hepatobil disorders-Other due to autoimmune hepatitis.

1 month ago

P2 data • IO biomarker • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)

TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • TP53 wild-type • STK11 mutation • ALK fusion • KEAP1 mutation • ROS1 fusion • KRAS G12 • STK11 mutation + TP53 mutation

FoundationOne® CDx

Lumakras (sotorasib)