News - KRAS G12C - LARVOL VERI

KontRASt-02: Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer (clinicaltrials.gov)

P3, N=95, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Sep 2026 | Trial primary completion date: Feb 2026 --> Aug 2026

1 day ago

Trial completion date • Trial primary completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

docetaxel • opnurasib (JDQ443)

KRASCENDO 3: A Study to Evaluate the Efficacy and Safety of Divarasib Compared With Investigator's Choice of Immunotherapy or Observation in Participants With Resected Stage II-III KRAS G12C-Positive Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)

P3, N=400, Not yet recruiting, Hoffmann-La Roche

1 day ago

New P3 trial

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Keytruda (pembrolizumab) • Opdivo (nivolumab) • divarasib (RG6330)

KontRASt-06: Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation. (clinicaltrials.gov)

P2, N=95, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2026 --> Nov 2027

1 day ago

Trial completion date • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)

PD-L1 expression • KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12

opnurasib (JDQ443)

A Study to Investigate the Safety and Efficacy of KQB368 as Monotherapy in Participants With Advanced Solid Malignancies (clinicaltrials.gov)

P1, N=48, Not yet recruiting, Kumquat Biosciences Inc.

1 day ago

New P1 trial

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12 • KRAS G12S

Sotorasib in Advanced KRAS G12C-Mutated NSCLC: Results From the Global Expanded Access Program, Including Patients With Poor Performance Status and a History of CNS Metastases. (PubMed, JTO Clin Res Rep)

Improvement from ECOG PS 2 to ECOG PS 0 to 1 was observed by the end of first cycle of treatment (57.9%). Safety and efficacy outcomes of sotorasib in this study were not affected with ECOG PS 2 and the history of CNS metastases and were consistent with those reported in key clinical trials.

2 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Lumakras (sotorasib)

Immunohistochemical Localization of Sotorasib-Protein Conjugates in the Rat Gastrointestinal Tract. (PubMed, Biol Pharm Bull)

Sotorasib-protein conjugates were strongly localized to the villous epithelial cells of the small intestine but were scarcely detected in the colon, highlighting regional differences. This study elucidates the localization of sotorasib-protein conjugates in the gastrointestinal tract of rats and provides important insights into the mechanisms underlying sotorasib-induced gastrointestinal disorders.

2 days ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS G12C • KRAS G12

Lumakras (sotorasib)

A Study to Learn About the Study Medicine PF-07934040 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Genetic Mutation. (clinicaltrials.gov)

P1, N=330, Recruiting, Pfizer | Trial completion date: Sep 2028 --> Jan 2029 | Trial primary completion date: Sep 2027 --> Jan 2028

2 days ago

Trial completion date • Trial primary completion date • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

KRAS mutation • KRAS G12C • KRAS G12

Keytruda (pembrolizumab) • Avastin (bevacizumab) • Erbitux (cetuximab) • cisplatin • carboplatin • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • pemetrexed • oxaliplatin • leucovorin calcium • Zumrad (sasanlimab)

KRAS inhibition is an effective therapy for appendiceal adenocarcinoma. (PubMed, bioRxiv)

We evaluated KRAS G12D -specific (MRTX1133) and pan-KRAS inhibitor (RMC-6236) in KRAS mut organoid and orthotopic PDX models of AA. Additionally, KRAS inhibition remodels TME and may enhance innate immune signaling. These findings support continued clinical development of KRAS inhibitors in AA and provide a rationale for combination strategies targeting resistance pathways and stromal remodeling.

5 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TGFB1 (Transforming Growth Factor Beta 1) • PDX1 (Pancreatic And Duodenal Homeobox 1) • CA 19-9 (Cancer antigen 19-9)

KRAS G12C • KRAS G12D

MRTX1133 • daraxonrasib (RMC-6236)

Integrating computational chemistry and machine learning to predict KRAS mutation-induced resistance. (PubMed, bioRxiv)

The models achieved over 90% accuracy and identified solvent-exposure and conformational changes at residues G10, E62, and H95 as key predictors of treatment resistance. This workflow offers a generalizable strategy for understanding and forecasting mutation-induced resistance.

5 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C

Clinicopathologic features of KRAS G12C-mutated non-small cell lung carcinomas:insights from 279 retrospective cases. (PubMed, Virchows Arch)

KRAS G12C-mutated NSCLC is clinically aggressive and frequently shows solid growth with rhabdoid, plasmacytoid, or SCC-like morphology, which may lead to misclassification and missed genetic testing. Immunohistochemistry and molecular profiling are essential for accurate classification and enabling targeted therapy.

7 days ago

Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • STK11 (Serine/threonine kinase 11) • NRG1 (Neuregulin 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • NKX2-1 (NK2 Homeobox 1) • GNAS (GNAS Complex Locus) • TP63 (Tumor protein 63) • NAPSA (Napsin A Aspartic Peptidase)

PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • STK11 mutation • FGFR2 mutation • MET mutation • NRG1 fusion • KRAS G12

NAPISTAR1-01: FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC (clinicaltrials.gov)

P1/2, N=174, Recruiting, Tubulis GmbH | N=120 --> 174

7 days ago

Enrollment change • Platinum resistant • First-in-human

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) • FOLR1 ( Folate receptor alpha ) • SLC34A2 (Solute carrier family 34 member 2) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • EGFR mutation • KRAS G12C • BRAF V600 • RET fusion • MET exon 14 mutation • ALK mutation • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • NTRK fusion