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BIOMARKER:

KRAS G12C + PD-L1 expression

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Entrez ID:
Related biomarkers:
1m
Real-World Study on Implementation of Genomic Tests for Advanced Lung Adenocarcinoma in Brazil. (PubMed, JCO Glob Oncol)
This study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of EGFR mutations, ALK fusions, and MET exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.
Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • 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)
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PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • PD-L1 overexpression • KRAS G12C • BRAF V600 • EGFR exon 20 insertion • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • KRAS G12 • EGFR exon 20 mutation • ALK-ROS1 fusion • KRAS G12C + PD-L1 expression
1m
KRas plays a negative role in regulating IDO1 expression. (PubMed, Transl Oncol)
Treatment with the KRasG12C-specific inhibitor, ARS-1620, significantly increased IDO1 expression, which inversely correlated with PD-L1 expression in the KRasG12C-mutant H358 cell line...Moreover, the induction of IDO1 expression following KRas inhibition appears to operate independently of the MAPK pathway. Our results propose that concurrent targeting of KRas and IDO1 could potentiate therapeutic efficacy in KRas-mutant cancers, overcoming resistance to immune checkpoint blockade.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • IDO1 (Indoleamine 2,3-dioxygenase 1)
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PD-L1 expression • KRAS G12C • RAS mutation • IDO1 expression • IFNG expression • KRAS G12C + PD-L1 expression • KRAS expression
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ARS-1620
1m
Trial primary completion date • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
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PD-L1 expression • KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12 • KRAS G12C + PD-L1 expression
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opnurasib (JDQ443)
2ms
FENIX-LCNEC study - Feasibility and efficacy of immunochemotherapy in correlation with genomic characteristics in large cell neuroendocrine carcinoma of the lung (DGHO 2024)
Here we present a case series of metastatic LCNEC in which favorable clinical courses with persistent response periods towards immunochemotherapy with nivolumab/ipilimumab/carboplatin and paclitaxel were achieved. The case series presented here underlines the feasibility and efficacy of combined ICI targeting PD-1 and CTLA-4 in combination with a platinum doublet in metastatic LCNEC. Despite the limited number of cases, we suggest the TMB to be a frequent and potentially characteristic marker in LCNEC that is well known to predict responsiveness towards immunochemotherapy.
Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • RECQL4( RecQ Like Helicase 4)
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PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • PTEN mutation • ARID1A mutation • KRAS G12 • KRAS G12C + PD-L1 expression • RECQL4 mutation
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TruSight Oncology 500 Assay
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Opdivo (nivolumab) • Yervoy (ipilimumab) • carboplatin • paclitaxel
5ms
Clinical
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PD-L1 expression • BRAF V600E • KRAS G12C • BRAF V600 • RET fusion • PD-L1 underexpression • ROS1 fusion • RET rearrangement • KRAS G12 • KRAS G12C + PD-L1 expression • PD-L1-L • NTRK fusion
5ms
Location of Metastases and Prognosis of Patients with Metastatic KRAS-Mutant Non-Small Cell Lung Cancer (IASLC-WCLC 2024)
Conclusions : In our cohort, KRAS -mutant patients appear to have a different metastatic pattern depending on their KRAS mutation subtype. In addition, KRAS G12C and KRAS G12V -mutant patients seem to have better prognosis and response to chemoimmunotherapy than KRAS G12D -mutant patients.
Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12 • KRAS G12C + PD-L1 expression • KRAS Q61L
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PD-L1 IHC 22C3 pharmDx • Oncomine™ Comprehensive Assay v3M • Oncomine Precision Assay
7ms
Enrollment closed
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
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PD-L1 expression • KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12 • KRAS G12C + PD-L1 expression
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opnurasib (JDQ443)
10ms
Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients. (PubMed, Thorac Cancer)
PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort.
Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world
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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)
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PD-L1 expression • PD-L1 overexpression • KRAS G12C • ALK positive • PD-L1 underexpression • PD-L1 negative • KRAS G12 • EGFR positive • KRAS G12C + PD-L1 expression • PD-L1-L
10ms
Sotorasib in KRAS G12C-mutated non-small cell lung cancer: A multicenter real-world experience from the compassionate use program in Germany. (PubMed, Eur J Cancer)
First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.
Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
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PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • STK11 mutation • KEAP1 mutation • KRAS G12 • KRAS G12C + PD-L1 expression
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Lumakras (sotorasib)
10ms
Extra-Hepatic Cholangiocarcinomas (ehCCA): a Genomic Landscape Comparison of Peri-Hilar (phCCA), Common Bile Duct (cbdCCA) and Gallbladder Cholangiocarcinomas (gbCCA) (USCAP 2024)
ehCCA subtypes feature characteristic GA profiles that have potential to influence therapy selection with significantly lower frequencies of FGFR2 and IDH1 when compared with iCCA. In contrast, targetable GA in ERBB2 and KRAS G12C are more frequent in ehCCA than iCCA, and highest in gbCCA and cbdCCA respectively. GA in IO drug response associated biomarker frequencies (MSI, TMB level and PD-L1 expression) are similar in all 3 ehCCA subgroups.
Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • 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) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
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PD-L1 expression • KRAS G12C • HRD • KRAS G12 • KRAS G12C + PD-L1 expression
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PD-L1 IHC 22C3 pharmDx
10ms
Extra-Hepatic Cholangiocarcinomas (ehCCA): a Genomic Landscape Comparison of Peri-Hilar (phCCA), Common Bile Duct (cbdCCA) and Gallbladder Cholangiocarcinomas (gbCCA) (USCAP 2024)
ehCCA subtypes feature characteristic GA profiles that have potential to influence therapy selection with significantly lower frequencies of FGFR2 and IDH1 when compared with iCCA. In contrast, targetable GA in ERBB2 and KRAS G12C are more frequent in ehCCA than iCCA, and highest in gbCCA and cbdCCA respectively. GA in IO drug response associated biomarker frequencies (MSI, TMB level and PD-L1 expression) are similar in all 3 ehCCA subgroups.
Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • 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) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
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PD-L1 expression • KRAS G12C • HRD • KRAS G12 • KRAS G12C + PD-L1 expression
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PD-L1 IHC 22C3 pharmDx
1year
P2 data • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
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PD-L1 expression • KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12 • KRAS mutation + STK11 mutation • KRAS G12C + PD-L1 expression • PD-L1 expression + STK11 mutation
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opnurasib (JDQ443)
1year
Peri-hilar cholangiocarcinoma (phCCA): A comparative comprehensive genomic profiling study. (ASCO-GI 2024)
phCCA appears to be a distinctive form of ehCCA featuring significantly higher frequencies of potentially targetable ERBB2 and lower frequencies of targetable FGFR2 and IDH1 mutations, when compared to ihCCA. Predictive IO markers were similarly low in both ihCCA and ehCCA. >
PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • 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) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
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PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • IDH1 mutation • HRD • FGFR2 mutation • KRAS G12 • KRAS G12C + PD-L1 expression
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PD-L1 IHC 22C3 pharmDx
1year
Tumor immune microenvironment of KRAS G12C mutated pancreatic cancer as compared to other mutations and non-cancer pancreata. (ASCO-GI 2024)
We identified increased infiltration of cytotoxic T lymphocytes and APCs in PDA patients with KRAS G12C mutations relative to other mutations and non-cancerous pancreata. Furthermore, while all PDAs had elevated PD-L1 expression on APCs, KRAS G12C tumors had minimal expression on epithelial cells suggesting a mutation specific impact and a potential role of immune checkpoint inhibitors in combination with G12C inhibitors.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD163 (CD163 Molecule) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
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PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12 • KRAS G12C + PD-L1 expression • KRAS expression
1year
Landscape of KRAS G12C Mutations in Genitourinary Malignancies (SUO 2023)
While KRAS G12C mutations are very rare in the major GU malignancies, a small proportion of such patients may benefit from emerging specific anti-KRAS G12C targeted therapies. Additionally, given the low prevalence of KRAS G12C mutations among major GU malignancies, investigation may be best approached in basket-type clinical trials using novel anti-KRAS G12C targeted therapies.
Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • TERT (Telomerase Reverse Transcriptase) • KDM6A (Lysine Demethylase 6A)
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PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12 • TERT mutation • KRAS G12C + PD-L1 expression
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PD-L1 IHC 22C3 pharmDx
1year
Characterization of a cohort of metastatic lung cancer patients harboring KRAS mutations treated with immunotherapy: differences according to KRAS G12C vs. non-G12C. (PubMed, Front Oncol)
Better overall survival and progression-free survival were observed in high PD-L1 expression tumors, regardless of KRAS mutation type. The heterogeneous nature of KRAS-mutant tumors and the presence of other co-mutations may contribute to different outcomes to immunotherapy-based strategies.
Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
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PD-L1 expression • KRAS mutation • PD-L1 overexpression • KRAS G12C • KRAS G12 • KRAS G12C + PD-L1 expression • KRAS expression • PD-L1 mutation
1year
Combined inhibition of KRAS G12C and PD-1 boosts the therapeutic efficacy via conditioning of tumor microenvironment in pre-clinical humanized NSCLC mouse models (SITC 2023)
Notably, AMG510 provided complementary immune modulatory benefits that support the mechanism of Nivolumab. The findings suggest that combining KRAS G12C inhibitor with anti-PD-1 antibody holds a promising therapeutic potential for NSCLC patients.
Preclinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • CD34 (CD34 molecule)
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KRAS mutation • PD-L1 overexpression • KRAS G12C • KRAS G12C + PD-L1 expression • KRAS expression
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Opdivo (nivolumab) • Lumakras (sotorasib)
1year
A real-world retrospective study of immunotherapy in NSCLC patients with KRAS mutation (SITC 2023)
Sotorasib and adagrasib are targeted drugs that have been proven effective and approved for KRAS G12C mutation, but they have not yet entered the Chinese market. Conclusions Bringing immunotherapy to first-line use in NSCLC patients with KRAS mutation might prolong their survival, and combination therapy is a preferable option compared to monotherapy. Positive PD-L1 expression and common KRAS mutations may serve as potential prognostic biomarkers for KRAS-mutated NSCLC patients who receive immunotherapy.
Retrospective data • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)
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PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • STK11 mutation • KRAS G12 • KRAS G12C + PD-L1 expression • KRAS expression • PD-L1 mutation
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Lumakras (sotorasib) • Krazati (adagrasib)