News - KRAS G12C - LARVOL VERI

A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov)

P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028

2 days ago

Enrollment open • Trial completion date • Trial primary completion date • First-in-human

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)

BRAF V600E • EGFR mutation • KRAS G12C • BRAF V600 • EGFR L858R • EGFR T790M • KRAS G12D • ALK rearrangement • MET exon 14 mutation • EGFR L861Q • ROS1 fusion • EGFR G719X • MET mutation • EGFR S768I • RET rearrangement • KRAS G12 • KRAS G12S • KRAS Q61

D3S-002 • elisrasib (D3S-001)

YKYY031，tumors: Phase I Clinical Trial of YKYY031 for Injection in Patients With Advanced Solid Tumors (clinicaltrials.gov)

P1, N=76, Not yet recruiting, Beijing Youcare Kechuang Pharmaceutical Technology Co., Ltd.

2 days ago

New P1 trial

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FBXW7 (F-Box And WD Repeat Domain Containing 7)

BRAF V600E • KRAS G12C • BRAF V600 • KRAS G12D • KRAS G13D • KRAS G12R • KRAS G12 • KRAS G12S • KRAS G13

Development and in vivo evaluation of 18F-labeled PET tracers covalently targeting KRAS-G12C for noninvasive cancer diagnosis and therapy monitoring. (PubMed, Theranostics)

[18F]KRAS490 showed specific, blockable tumor uptake and favorable pharmacokinetics, making it a promising tracer for noninvasive imaging of KRAS-G12C mutant tumors. Its ability to penetrate the CNS supports potential application in imaging both peripheral and brain lesions.

5 days ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Krazati (adagrasib)

Discovery of Highly Potent and Selective SOS1 Inhibitors for the Treatment of KRAS-Driven Colorectal Cancer. (PubMed, J Med Chem)

At doses of 60 mg/kg, they achieved significant tumor growth inhibition (75.1% and 86.2%, respectively) in HCT116 xenograft models without significant toxicity. Collectively, this study identifies potent drug candidates with strong pan-KRAS therapeutic efficacy against colorectal cancer.

5 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS G12C

A First-in-Human Trial of BLU-924 (SAR449336) in Advanced Solid Tumors Harboring KRAS Mutations (clinicaltrials.gov)

P1/2, N=265, Recruiting, Blueprint Medicines Corporation

5 days ago

New P1/2 trial • First-in-human

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12 • KRAS G12S • KRAS G13

Targeting GSTZ1 sensitizes KRAS G12C-mutant lung cancer cells by overcoming glutathione and glycolysis pathway rewiring. (PubMed, Cancer Res Commun)

These metabolic shifts were accompanied by increased AMPK phosphorylation and reduced AKT phosphorylation, two key mediators of the response to KRAS G12C inhibition. Our data reveal GSTZ1‑associated metabolic and signaling alterations that contribute to drug resistance and identify GSTZ1 as a potential complementary target to sensitize KRAS mutant NSCLC to KRAS‑directed treatments.

6 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1)

KRAS mutation • KRAS G12C • KRAS G12

Prognostic Significance of KRAS G12C Versus Non-G12C RAS Mutations in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. (PubMed, Oncologist)

KRAS G12C mutations represent an independent adverse prognostic biomarker in mCRC, with a statistically significant 28% increased risk of mortality compared to other RAS mutations. The consistent hazard ratio across multiple sensitivity analyses supports a true prognostic effect. These findings have important implications for patient counseling and risk stratification. While the poor prognosis may provide rationale for prioritizing trial enrollment, translation into therapeutic decision-making requires caution, as prospective data demonstrating benefit from earlier use of KRAS G12C inhibitors are lacking.

7 days ago

Retrospective data • Journal

KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)

KRAS mutation • KRAS G12C • RAS mutation • KRAS G12

A Clinical Trial of Calderasib (MK-1084) and Durvalumab in People With Non-Small Cell Lung Cancer (MK-1084-015/KANDLELIT-015) (clinicaltrials.gov)

P3, N=310, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

7 days ago

Enrollment open

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Imfinzi (durvalumab) • calderasib (MK-1084)

A Study of BMS-986488 as Monotherapy and Combination Therapy in Participants With Advanced Malignant Tumors (clinicaltrials.gov)

P1, N=437, Recruiting, Bristol-Myers Squibb | Active, not recruiting --> Recruiting

7 days ago

Enrollment open

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Opdivo (nivolumab) • Erbitux (cetuximab) • Krazati (adagrasib)

Real-world comparative effectiveness of sotorasib versus docetaxel monotherapy in second line and beyond for advanced or metastatic non-small cell lung cancer: A national database analysis from England. (PubMed, Lung Cancer)

Sotorasib was associated with significantly improved OS, TTNTD, and TTDD compared with docetaxel in 2 L+ for locally advanced or metastatic NSCLC under real-world conditions in England.

8 days ago

Journal • HEOR • Real-world evidence

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

docetaxel • Lumakras (sotorasib)

Subtype-Specific Alterations in Copper Trafficking Associated with KRAS Mutations in Isogenic Colorectal Cancer Cell Lines. (PubMed, Biol Trace Elem Res)

Notably, the copper chelator ammonium tetrathiomolybdate inhibited cell growth in all KRAS-mutant cells. Our results suggest that KRAS-mutant colorectal cancer cells are sensitive to perturbations in copper homeostasis in a mutation subtype-specific manner.

8 days ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase) • ATP7A (ATPase Copper Transporting Alpha)

KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12

BBO-11818 in Adult Subjects With KRAS Mutant Cancer (clinicaltrials.gov)

P1, N=665, Recruiting, TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) | N=387 --> 665

8 days ago

Enrollment change • First-in-human

KRAS (KRAS proto-oncogene GTPase)

KRAS G12C • KRAS G12D • KRAS G12 • KRAS G12S

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