The SACHI trial demonstrated that savolitinib plus osimertinib nearly doubled progression-free survival (PFS) compared with chemotherapy (9.8 vs. 5.4 months; hazard ratio 0.34) in patients with EGFR-mutated, MET-amplified non-small-cell lung cancer (NSCLC) after EGFR tyrosine kinase inhibitor (TKI) failure-the first phase 3 evidence for dual EGFR/MET inhibition in this setting.1.

10 days ago

Journal

EGFR (Epidermal growth factor receptor)

EGFR mutation • MET amplification • MET mutation

Tagrisso (osimertinib) • Orpathys (savolitinib)

10d

Genomic landscape and homologous recombination deficiency in malignant germ cell tumors reveals sex-specific therapeutic opportunities. (PubMed, J Pathol)

This study underscores the presence of sex-specific therapeutic vulnerabilities in GCTs, which warrant further exploration in larger cohorts.

10 days ago

Journal • BRCA Biomarker • PARP Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • HRD (Homologous Recombination Deficiency) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)

TP53 mutation • MET amplification • HRD • ROS1 fusion

13d

Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN) (clinicaltrials.gov)

P2, N=197, Recruiting, Gruppo Oncologico del Nord-Ovest | N=140 --> 197

13 days ago

Enrollment change

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

HER-2 positive • MSI-H/dMMR • KRAS G12C • HER-2 amplification • HER-2 mutation • MET amplification • POLE mutation • KRAS wild-type • RAS wild-type • KRAS G12 • POLD1 mutation • HER-2 positive + HER-2 overexpression • HER-2 positive + RAS wild-type

Opdivo (nivolumab) • Imfinzi (durvalumab) • Vectibix (panitumumab) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Lumakras (sotorasib) • balstilimab (AGEN2034) • botensilimab (AGEN1181) • vorbipiprant (CR6086)

13d

MET-Driven Resistance to Sotorasib in KRAS G12C-Mutant NSCLC and Response to Combined KRAS and MET Inhibition. (PubMed, JTO Clin Res Rep)

Notably, one patient with acquired MET amplification achieved a renewed partial response to the combination of sotorasib and tepotinib after progression on sotorasib monotherapy. Our findings support rebiopsy at progression on sotorasib. Further prospective trials are warranted to validate MET amplification as a resistance mechanism and to define optimal therapeutic thresholds for combined KRAS and MET inhibition.

13 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • MET amplification • MET mutation • KRAS G12

Lumakras (sotorasib) • Tepmetko (tepotinib)

19d

ELIOS: A Multicenter, Molecular Profiling Study of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer Treated with First-Line Osimertinib. (PubMed, Cancer Discov)

In a separate analysis of patients with matched tissue and plasma samples post-progression (n = 51), 82% had potential resistance alterations by NGS, demonstrating the complementary roles of tissue and plasma NGS. These results highlight the challenges of obtaining tissue biopsies in patients with NSCLC progressing on targeted therapy, the potential for heterogeneous resistance and the need for broad-acting treatment strategies.

19 days ago

Journal

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)

EGFR mutation • MET amplification • CDKN2A deletion

Tagrisso (osimertinib)

21d

Study of MCLA-129 in Combination With Ensartinib in Patients With Advanced Solid Tumors. (clinicaltrials.gov)

P1/2, N=164, Recruiting, Betta Pharmaceuticals Co., Ltd.

21 days ago

New P1/2 trial

MET (MET proto-oncogene, receptor tyrosine kinase) • CLDN18 (Claudin 18)

HER-2 positive • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • MET exon 14 mutation • MET overexpression • MET mutation

Ensacove (ensartinib) • pamvatamig (MCLA-129)

26d

Do targeted NGS panels include NSCLC guideline-recommended biomarkers? (PubMed, Am J Manag Care)

Of 77 unique panels evaluated, only 5 captured all recommended biomarkers for mNSCLC. Ensuring targeted panels assess all relevant biomarkers is crucial for optimal patient treatment.

26 days ago

Journal • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • 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) • NTRK (Neurotrophic receptor tyrosine kinase)

MET amplification • MET exon 14 mutation • NTRK fusion

30d

Lazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment (clinicaltrials.gov)

P2, N=47, Recruiting, Samsung Medical Center | Not yet recruiting --> Recruiting

30 days ago

Enrollment open

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification

Tepmetko (tepotinib) • Lazcluze (lazertinib)

Recurrent Escape from Osimertinib-Induced Senescence Promotes Genomic Instability Associated with Therapeutic Resistance. (PubMed, bioRxiv)

Despite profound genomic instability, targeting DNA repair or replication stress pathways was ineffective, whereas sensitivity to platinum-based chemotherapy was retained across clades. Collectively, these findings indicate that recurrent senescence escape drives osimertinib resistance through widespread genomic instability and is most effectively treated by cytotoxic strategies rather than pathway-targeted approaches.

1 month ago

Journal • Tumor mutational burden

EGFR (Epidermal growth factor receptor) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • MET amplification • MET mutation

Tagrisso (osimertinib) • simmitinib (SYHA1817)

A MET-Targeted Variable New Antigen Receptor (VNAR) Theranostic for Non-Small Cell Lung Cancer. (PubMed, bioRxiv)

Together, these findings establish vMET1-Fc as a theranostic agent for imaging and treating MET-altered NSCLC. A shark-derived antibody selectively targeting MET shows preclinical efficacy as a theranostic agent for MET-altered cancers.

1 month ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET mutation • MET expression • MET positive

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov)

P2, N=367, Active, not recruiting, AstraZeneca | Trial completion date: May 2025 --> Dec 2026

1 month ago

Trial completion date

MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • MET overexpression

Tagrisso (osimertinib) • Orpathys (savolitinib)