News - NRAS G12 - LARVOL VERI

22h

FALCO: Neoadjuvant Treatment of Fulzerasib Plus Cetuximab N01 in KRAS G12C Mutated Locally Advanced Colorectal Cancer With or Without Resectable Metastases (clinicaltrials.gov)

P2, N=40, Recruiting, Zhejiang University

22 hours ago

New P2 trial

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)

KRAS mutation • KRAS G12C • BRAF mutation • NRAS mutation • BRAF wild-type • KRAS G12 • NRAS wild-type • NRAS G12

Erbitux (cetuximab) • Dupert (fulzerasib) • Datalai (cetuximab biosimilar)

Dual inhibition of GTP-bound (ON) and GDP-bound (OFF) KRAS G12C suppresses PI3Kα and leads to potent tumor inhibition. (PubMed, bioRxiv)

BBO-8520 exerted more potent and sustained inhibition of KRAS G12C and anti-tumor activity in vitro and in vivo compared with sotorasib, a KRAS G12C (OFF)-only inhibitor...Moreover, in some contexts, disruption of RAS-PI3Kα further increased the anti-tumor activity of BBO-8520 monotherapy. These results reveal mechanistic differences between KRAS (ON) and (OFF) inhibitors, highlight the importance of PI3Kα-AKT signaling in driving resistance to KRAS inhibition in lung cancer, and suggest combination strategies that suppress PI3Kα-AKT to improve the response to KRAS inhibitors.

6 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

KRAS mutation • KRAS G12C • RAS wild-type • NRAS wild-type • NRAS G12

Lumakras (sotorasib)

17d

BDTX-4933-101: A Study of S241656 in Patients With KRAS, BRAF and Other Selected RAS/MAPK Mutation-Positive Malignancies (2025-523474-16-00)

P1/2, N=105, Not yet recruiting, Institut De Recherches Internationales Servier IRIS

17 days ago

New P1/2 trial

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase)

KRAS mutation • KRAS G12C • BRAF mutation • RAS mutation • KRAS G12 • NRAS G12

Erbitux (cetuximab) • gemcitabine • 5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • irinotecan • S241656

19d

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

19 days ago

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)

Rare internal malignancies in xeroderma pigmentosum: A report of two cases from Tunisia and analysis of driver mutations. (PubMed, Cancer Pathog Ther)

In this study, targeted next-generation sequencing using the AmpliSeq for Illumina Cancer HotSpot Panel identified pathogenic mutations in canonical cancer driver genes: tumor protein p53 (TP53) NM_000546.6:c.730G>T (p.Gly244Cys) and platelet-derived growth factor receptor alpha (PDGFRA) NM_006206.6:c.2525A>T (p.Asp842Val) mutations in renal leiomyosarcoma and NRAS proto-oncogene, GTPase (NRAS) NM_002524.5:c.35G>T (p.Gly12Val) mutation in the ovarian tumor. These findings suggest a potential benefit of personalized therapies for XP patients with internal malignancies.

1 month ago

Journal

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • XPC (XPC Complex Subunit, DNA Damage Recognition And Repair Factor)

TP53 mutation • NRAS mutation • PDGFRA mutation • NRAS G12

2ms

19-C-0017: Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients (clinicaltrials.gov)

P1/2, N=5, Completed, National Cancer Institute (NCI) | N=70 --> 5 | Recruiting --> Completed

2 months ago

Trial completion • Enrollment change • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

PD-L1 expression • KRAS mutation • NRAS mutation • KRAS G12D • EGFR expression • HRAS mutation • KRAS G12 • NRAS G12

cyclophosphamide • fludarabine IV • Proleukin (aldesleukin) • anti-KRAS G12D mTCR PBL

2ms

Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer (clinicaltrials.gov)

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027

2 months ago

Trial completion date

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

KRAS mutation • NRAS mutation • BRAF V600 • BRAF wild-type • RAS wild-type • HRAS mutation • KRAS G12 • NRAS Q61 • KRAS G13 • NRAS G12 • NRAS G13 • KRAS Q61

Mekinist (trametinib) • omipalisib (GSK2126458)

2ms

Cutaneous Epithelioid/Pleomorphic Rhabdomyosarcoma, Melanoma in Disguise? An Immunohistochemical, Molecular and Epigenetic Study of 13 Patients. (PubMed, Mod Pathol)

The majority of cutaneous epithelioid/pleomorphic rhabdomyosarcoma show clinical, genetic, and epigenetic profiles similar to melanoma, suggesting that a major subset represents transdifferentiated melanoma.

2 months ago

Journal • Tumor mutational burden

BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • TFCP2 (Transcription Factor CP2)

BRAF V600E • NRAS Q61 • NRAS G12

2ms

Retrospective Comparison of Operational Metrics Across Diagnostic Approaches for Molecular Testing in Lung and Colon Cancers in a Community-Based Setting. (PubMed, Arch Pathol Lab Med)

OFA balances TAT, QNS, and detection, whereas SO-NGS offers comprehensive detection with longer TAT and higher QNS. An optimized assay combining SGP's speed, OFA's reliability, and SO-NGS's comprehensiveness could improve outcomes.

2 months ago

Retrospective data • 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) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • 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) • TYK2 (Tyrosine Kinase 2) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS G12C • HER-2 amplification • HER-2 mutation • MET exon 14 mutation • KRAS G12 • KRAS amplification • NRAS G12

Oncomine Focus Assay

3ms

The polyamine inhibitor SAM486A increases the efficacy of adagrasib in non-small cell lung cancer cells harboring KRASG12C mutation. (PubMed, Biol Res)

Our results suggest that targeting polyamine metabolism with SAM486A enhances the efficacy of KRASG12C inhibitors and may mitigate resistance. This combination represents a promising therapeutic approach for KRASG12C-mutant NSCLC and warrants further clinical investigation.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • PCNA (Proliferating cell nuclear antigen)

KRAS mutation • KRAS G12C • KRAS wild-type • RAS wild-type • KRAS G12 • NRAS Q61 • NRAS G12

Krazati (adagrasib)

3ms

Structure-Guided Development of NRAS G12D Inhibitors Based on a 5‑Azaindole Core. (PubMed, ACS Med Chem Lett)

The development process revealed key insights into gaining selectivity between NRAS and KRAS proteins. Notably, stabilization of the p-loop and substitution toward Leu 95 while maintaining key interactions with Asp12, Gly60, and Asp69 improved NRAS G12D potency and resulted in selectivity against wild-type KRAS/non-responder.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)

NRAS mutation • KRAS G12D • KRAS wild-type • RAS wild-type • KRAS G12 • NRAS G12

3ms

Revealing conformational changes of GTP-bound NRAS mutants probed by GaMD and Markov state models. (PubMed, Phys Chem Chem Phys)

Furthermore, mutations induce specific changes in the protein's internal communication networks. These insights into the dynamic properties of oncogenic NRAS mutants provide a robust mechanistic foundation for understanding aberrant signaling and guiding the rational design of novel anti-cancer therapeutics.

3 months ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog)

NRAS mutation • RAS wild-type • NRAS Q61 • NRAS wild-type • NRAS G12