News - KRAS mutation + STK11 mutation

11ms

A Phase II Trial of JDQ443 in KRAS G12C-Mutated NSCLC with PD-L1 Expression <1% or PD-L1 Expression ≥1% and an STK11 Co-Mutation (MTCS 2023)

TBD

11 months ago

P2 data • PD(L)-1 Biomarker • 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 • KRAS mutation + STK11 mutation • KRAS G12C + PD-L1 expression • PD-L1 expression + STK11 mutation

opnurasib (JDQ443)

over1year

STK11 mutations predict poor prognosis for advanced NSCLC treated with first-line immunotherapy or chemo-immunotherapy according to KRAS, TP53, KEAP1, and SMARCA4 status (ESMO 2023)

Conclusions STK11 aberrations hampered the mOS of nsq NSCLC pts treated with first-line IO or CT-IO. The negative prognostic impact seems to be unrelated to IO administration.

over 1 year ago

Clinical • IO biomarker • Metastases

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)

TP53 mutation • KRAS mutation • STK11 mutation • KEAP1 mutation • KRAS mutation + STK11 mutation

over1year

A Critical Review of the Prognostic and Predictive Implications of KRAS and STK11 Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer. (PubMed, J Pers Med)

However, KRAS/STK11 co-mutations may predict primary resistance to ICI. Prospective KRAS/STK11-biomarker-driven randomized trials are needed to assess the predictive effect of various treatments on the outcomes for patients with metastatic NSCLC, as the majority of the published KRAS analyses are retrospective and hypothesis-generating in nature.

over 1 year ago

Review • Journal • IO biomarker • Metastases

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)

KRAS mutation • STK11 mutation • KRAS mutation + STK11 mutation

over1year

A phase II trial of JDQ443 in KRAS G12C-mutated NSCLC with PD-L1 expression <1% or PD-L1 expression ≥1% and an STK11 co-mutation. (ASCO 2023)

Reused with permission. Clinical trial information: NCT05445843.

over 1 year ago

P2 data • PD(L)-1 Biomarker • 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 • KRAS mutation + STK11 mutation • PD-L1 expression + STK11 mutation

opnurasib (JDQ443)

over1year

Clinical Next-Generation Sequencing Panels Reveal Molecular Differences Between Merkel Cell Polyomavirus-Negative Merkel Cell Carcinomas and Neuroendocrine Carcinomas. (PubMed, Am J Clin Pathol)

High tumor mutational burden and UV signature, as well as the presence of NF1 and PIK3CA mutations, are supportive of MCPyV-negative MCC, whereas KEAP1, STK11, and KRAS mutations are supportive of NEC in the appropriate clinical context. Although rare, the presence of a gene fusion is supportive of NEC.

over 1 year ago

Journal • Next-generation sequencing • Tumor mutational burden

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • TSC1 (TSC complex subunit 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)

KRAS mutation • TMB-H • PIK3CA mutation • STK11 mutation • NF1 mutation • KEAP1 mutation • KRAS mutation + STK11 mutation • TSC1 mutation

over1year

A Phase II trial of JDQ443 in KRAS G12C-mutated NSCLC with PD-L1 expression <1% or PD-L1 expression≥1% and an STK11 co-mutation (AACR 2023)

Other secondary endpoints include progression-free survival, overall survival, safety, pharmacokinetics, and pt-reported outcomes. A comprehensive biomarker strategy aims to investigate predictors of treatment response and resistance in the study population.

over 1 year ago

P2 data • PD(L)-1 Biomarker • 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 • KRAS mutation + STK11 mutation • PD-L1 expression + STK11 mutation

opnurasib (JDQ443)

almost2years

Identifying novel vulnerabilities to sensitise -mutant lung adenocarcinoma to T cell mediated killing (LCC 2023)

Recent investigations validating the ability of candidate genes to sensitise KL tumour cells to T cell killing will be presented. Together, these results demonstrate the power of whole genome CRISPR screens in identifying candidate genes that may serve as therapeutic targets to improve treatment responses in KRAS / STK11/Lkb1 mutant LUAD patients.

almost 2 years ago

PD(L)-1 Biomarker • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin) • JAK1 (Janus Kinase 1) • STAT1 (Signal Transducer And Activator Of Transcription 1) • IFNGR1 (Interferon Gamma Receptor 1)

KRAS mutation • KRAS G12D • STK11 mutation • KRAS G12 • KRAS mutation + STK11 mutation

almost2years

Nivolumab (nivo) + Doublet of chemotherapy based on platinum salts (chemo) versus chemo, in neoadjuvant treatment of bronchial cancer not with small cells (CBNPC) resistable (IB-IIIA): correlation between survival without event (EFS) and regression pathological in the CheckMate 816 study (CPLF 2023)

Abstract previously presented at the ASCO Congress (American Society of Clinical Oncology), June 3-7, 2022, Chicago, United States. Journal of Clinical ONCOLOGY 2022 40: 17_SUPPL, LBA9026.

almost 2 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11)

KRAS mutation • STK11 mutation • KRAS wild-type • RAS wild-type • KRAS mutation + STK11 mutation

Opdivo (nivolumab)

almost2years

Nivolumab (nivo) + ipilimumab (IPI) + 2 cycles of chemotherapy (chemo) VS Chimio alone (4 cycles) in 1st line of treatment (1L) of bronchial cancer not with small cells (CBNPC) Metastatic: data updated at 3 years The CheckMate 9LA study (CPLF 2023)

Abstract previously presented at the ASCO Congress (American Society of Clinical Oncology), June 3-7, 2022, Chicago, United States. Journal of Clinical ONCOLOGY 2022 40: 17_SUPPL, LBA9026.

almost 2 years ago

PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11)

KRAS mutation • STK11 mutation • KRAS wild-type • RAS wild-type • KRAS mutation + STK11 mutation

Opdivo (nivolumab) • Yervoy (ipilimumab)

almost2years

First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of chemotherapy (chemo) vs chemo alone (4 cycles) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC): 3-year update from CheckMate 9LA (DKK 2022)

Pts with non-squamous (NSQ) NSCLC in the chemo arm could receive pemetrexed maintenance. With a 3-y minimum f/u, 1L NIVO + IPI + chemo demonstrated long-term, durable efficacy benefit vs chemo in pts with mNSCLC. Survival benefit of NIVO + IPI + chemo vs chemo was seen regardless of KRAS and STK11 mutation status.

almost 2 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11)

PD-L1 expression • STK11 mutation • KRAS wild-type • KRAS mutation + STK11 mutation

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • pemetrexed

over2years

Wide Next-Generation Sequencing Characterization of Young Adults Non-Small-Cell Lung Cancer Patients. (PubMed, Cancers (Basel))

Conversely, EGFR and EML4-ALK alterations were more frequently found in tumors with low TMB (p = 0.019 and p < 0.001, respectively). We compared results obtained from this approach with those obtained from a single or few genes approach, observing perfect concordance of the results.

over 2 years ago

Journal • Next-generation sequencing • Tumor Mutational Burden

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • EML4 (EMAP Like 4) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

KRAS mutation • EGFR mutation • TMB-H • STK11 mutation • TMB-L • KRAS mutation + STK11 mutation

over2years

First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients (pts) with metastatic non–small cell lung cancer (NSCLC): 3-year update from CheckMate 9LA. (ASCO 2022)

Pts with non-squamous (NSQ) NSCLC in the chemo-alone arm could receive pemetrexed maintenance. With a 3-year minimum follow-up, 1L NIVO + IPI + chemo demonstrated long-term, durable efficacy benefit vs chemo in pts with metastatic NSCLC. Survival benefit of NIVO + IPI + chemo vs chemo was observed regardless of KRAS and STK11 mutation status.

over 2 years ago

Late-breaking abstract • Clinical • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • STK11 (Serine/threonine kinase 11)

PD-L1 expression • STK11 mutation • KRAS wild-type • KRAS mutation + STK11 mutation

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • pemetrexed

almost3years

Somatic mutations, germline risk and ancestry in lung adenocarcinoma (AACR 2022)

If we find a germline locus or loci that could impact the development of lung cancers with EGFR and/or KRAS mutation, this might help in improving lung cancer prevention and screening for populations of Latin American origin and others. Furthermore, multiple studies now highlight the importance of EGFR mutation screening and EGFR-directed targeted therapy for lung cancer patients in Latin America and with origins in Latin America.

almost 3 years ago

Tumor Mutational Burden

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • TERT (Telomerase Reverse Transcriptase)

KRAS mutation • EGFR mutation • STK11 mutation • KRAS mutation + STK11 mutation • EGFR mutation + KRAS mutation

over3years

[VIRTUAL] Differences of immune microenvironment among NSCLC patients with various KRAS mutation types (ESMO 2021)

The different response to ICI in patients with KRAS mutation, co-mutation with STK11 can be explained by the difference in TIME, which including immune cells infiltrated, PD-L1 expression.

over 3 years ago

Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8)

PD-L1 expression • KRAS mutation • STK11 mutation • KRAS mutation + STK11 mutation

PD-L1 IHC 22C3 pharmDx

4years

A Potential Biomarker of Combination of Tumor Mutation Burden and Copy Number Alteration for Efficacy of Immunotherapy in KRAS-Mutant Advanced Lung Adenocarcinoma. (PubMed, Front Oncol)

The combination of TMB and CNA provides more sensible and accurate prediction of ICI response than individual factors in KRAS-mutant LUAD. Moreover, low TMB and high CNA can be utilized as a potential biomarker to predict adverse outcome in KRAS-mutant LUAD.

4 years ago

Clinical • Journal • Tumor Mutational Burden

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11)

TP53 mutation • KRAS mutation • KRAS G12C • STK11 mutation • TMB-L • KRAS G12 • KRAS mutation + STK11 mutation

4years

Response to Checkpoint Inhibition in Non-Small Cell Lung Cancer with Molecular Driver Alterations. (PubMed, Oncol Res Treat)

Molecular testing may be of use in guiding treatment decision making in NSCLC.

4 years ago

Journal • Checkpoint inhibition

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1)

TP53 mutation • KRAS mutation • EGFR mutation • PIK3CA mutation • MET exon 14 mutation • STK11 mutation • NF1 mutation • KRAS mutation + STK11 mutation • EGFR mutation + KRAS mutation

Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab)

4years

Rapid progressive lung cancers harbouring multiple clonal driver mutations with big bang evolution model. (PubMed, Cancer Genet)

We should pay attention to clinical course of lung cancer patients harboring multiple clonal driver mutations in their primary lesions. Their punctuated and big bang evolutionary process could develop systemic clinically undetectable metastases with an unexpected speed.

4 years ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • CREBBP (CREB binding protein)

TP53 mutation • KRAS mutation • PTEN mutation • STK11 mutation • KEAP1 mutation • KRAS mutation + STK11 mutation • KRAS Q61H

4years

Intraductal papillary neoplasms of the bile duct are consisted of two distinct types specifically associated with clinicopathological features and molecular phenotypes. (PubMed, J Pathol)

Mutations in KRAS and GNAS were enriched in the type 1 IPNBs while mutations in TP53, SMAD4 and KMT2C were enriched in the type 2 IPNBs. These results indicate that IPNBs are consisted of two distinct types of neoplasms specifically associated with clinicopathological features and molecular phenotypes.

4 years ago

Clinical • Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • STK11 (Serine/threonine kinase 11) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • GNAS (GNAS Complex Locus) • ELF3 (E74 Like ETS Transcription Factor 3)

TP53 mutation • KRAS mutation • STK11 mutation • PBRM1 mutation • KRAS mutation + STK11 mutation • RNF43 mutation

4years

Neoadjuvant nivolumab plus ipilimumab in resectable non-small cell lung cancer. (PubMed, J Immunother Cancer)

Though treatment was feasible, due to toxicity the study arm was terminated early by investigator consensus. In light of this, and while the long-term disease-free status of patients who achieved pCR is encouraging, further investigation of neoadjuvant nivolumab plus ipilimumab in patients with resectable NSCLC requires the identification of predictive biomarkers that enrich for response.

4 years ago

Clinical • Journal • Tumor Mutational Burden • PD(L)-1 Biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)

PD-L1 expression • KRAS mutation • STK11 mutation • KEAP1 mutation • KRAS mutation + STK11 mutation • KEAP1 mutation + KRAS mutation • TMB + PD-L1 expression

Opdivo (nivolumab) • Yervoy (ipilimumab)

4years

Specific TP53 subtype as biomarker for immune checkpoint inhibitors in lung adenocarcinoma. (PubMed, EBioMedicine)

Our study demonstrated that not all TP53 mutations are equal in predicting efficacy in patients with LUAD treated with ICIs. Multi-center data showed that TP53 missense and nonsense mutations were significantly different in terms of associations with PD-L1 expression, IFN-γ signatures and TME composition. Special attention should be paid to potential TP53 mutation heterogeneity when evaluating TP53 status as biomarker for ICIs.

4 years ago

Journal • Checkpoint inhibition • Tumor Mutational Burden • PD(L)-1 Biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)

PD-L1 expression • TP53 mutation • KRAS mutation • ATM mutation • STK11 mutation • KRAS mutation + STK11 mutation • EGFR mutation + KRAS mutation

Opdivo (nivolumab) • Yervoy (ipilimumab)

4years

Clinicopathological and Molecular Differences Between Gastric-type Mucinous Carcinoma and Usual-type Endocervical Adenocarcinoma of the Uterine Cervix. (PubMed, Cancer Genomics Proteomics)

GMC is associated with more aggressive behavior than UEA. Distinctive p53 and p16 immunostaining patterns enable differential diagnosis. GMC and UEA exhibit genetic heterogeneity with potentially actionable molecular alterations.

4 years ago

Clinical • Journal • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • KRAS mutation • BRCA2 mutation • PIK3CA mutation • ARID1A mutation • STK11 mutation • NF1 mutation • MDM2 amplification • PIK3CA amplification • HRAS mutation • KRAS mutation + STK11 mutation • PIK3CA mutation + HRAS mutation

over4years

Comprehensive Clinical and Genetic Characterization of Hyperprogression Based on Volumetry in Advanced Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor. (PubMed, J Thorac Oncol)

Defining HPD treated with ICI based on volumetric measurement is more precise than that based on one-dimensional analysis. Pre-ICI dNLR, LDH, and concurrence of STK11 and KRAS mutations could, thus, be used as potential biomarkers for HPD prediction.

over 4 years ago

Clinical • Journal • Checkpoint inhibition

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)

KRAS mutation • STK11 mutation • KRAS mutation + STK11 mutation

over4years

[VIRTUAL] Distinct Landscapes of Genomic Alterations between Lung Carcinoids and Non-Small Cell Lung Cancers (ESHG 2020)

Molecular profiles in NSCLC and LC are substantially different and this may have direct consequences in the therapy decision process. For example, preferential loss of the CDKN2A locus in NSCLC could impact the response to immunotherapy drugs. In contrast, as MDM2 is a negative regulator of TP53 , MDM2 amplification in NSCLC could indicate therapeutic efficacy of MDM2 inhibitors in p53 mutant tumours.

over 4 years ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KEAP1 (Kelch Like ECH Associated Protein 1) • SOX2

TP53 mutation • KRAS mutation • STK11 mutation • MDM2 amplification • CDKN2A deletion • KEAP1 mutation • KRAS mutation + STK11 mutation • MDM2 mutation • miR-138 underexpression + miR-497 overexpression

over4years

Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer. (PubMed, Lung Cancer)

Targeted sequencing of plasma ctDNA and monitoring its early variations can predict response to ICI.

over 4 years ago

Journal • Tumor Mutational Burden • PD(L)-1 Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11)

TP53 mutation • PTEN mutation • STK11 mutation • KRAS mutation + STK11 mutation

over4years

The Genomic Landscape of SMARCA4 Alterations and Associations with Outcomes in Patients with Lung Cancer. (PubMed, Clin Cancer Res)

SMARCA4 alterations can be divided into two clinically relevant genomic classes associated with differential protein expression as well as distinct prognostic and treatment implications. Both classes co-occur with KEAP1, STK11, and KRAS mutations, but individually represent independent predictors of poor prognosis. Despite association with poor outcomes, SMARCA4-mutant lung cancers may be more sensitive to immunotherapy.

over 4 years ago

Clinical • Journal

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)

KRAS mutation • STK11 mutation • KEAP1 mutation • KRAS mutation + STK11 mutation • SMARCA4 mutation • KEAP1 mutation + KRAS mutation

over4years

[VIRTUAL] IMpower150: A post hoc analysis of efficacy outcomes in patients with KRAS, STK11 and KEAP1 mutations (ESMO 2020)

In the randomised, phase III IMpower150 study, atezolizumab (A) + bevacizumab (B) + carboplatin/paclitaxel (CP) chemotherapy significantly prolonged PFS and OS vs BCP in patients (pts) with first-line non-squamous NSCLC. Funding: F. Hoffmann-La Roche, Ltd. Clinical trial identification: NCT02366143.

over 4 years ago

Clinical • Retrospective data • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)

STK11 mutation • KEAP1 mutation • KRAS mutation + STK11 mutation • EGFR mutation + KRAS mutation

Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • paclitaxel

over4years

[VIRTUAL] FGFR1-4 mutations are associated with immunotherapy outcomes in patients with non-small cell lung cancer (ESMO 2020)

Legal entity responsible for the study: The authors. Funding: Has not received any funding.

over 4 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11)

PD-L1 expression • TP53 mutation • KRAS mutation • STK11 mutation • ALK mutation • FGFR1 mutation • KRAS mutation + STK11 mutation

over4years

[VIRTUAL] Clinical relevance of somatic and germline alterations in patients with pancreatic ductal adenocarcinoma (ESMO 2020)

Legal entity responsible for the study: The authors. Funding: Has not received any funding.

over 4 years ago

Clinical • BRCA Biomarker • PARP Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SF3B1 (Splicing Factor 3b Subunit 1) • PALB2 (Partner and localizer of BRCA2) • RNF43 (Ring Finger Protein 43) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • JAK1 (Janus Kinase 1) • JAK3 (Janus Kinase 3)

TP53 mutation • BRCA1 mutation • STK11 mutation • PALB2 mutation • SF3B1 mutation • CDKN2A mutation • KRAS mutation + STK11 mutation • JAK3 mutation

over4years

[VIRTUAL] Neoadjuvant atezolizumab (A) for resectable non-small cell lung cancer (NSCLC): results from the phase II PRINCEPS trial. (ESMO 2020)

Funding: Roche-Genentech. Clinical trial identification: NCT02994576.

over 4 years ago

P2 data • Clinical • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)

TP53 mutation • KRAS mutation • EGFR mutation • STK11 mutation • KRAS mutation + STK11 mutation • EGFR mutation + KRAS mutation

VENTANA PD-L1 (SP142) Assay

Tecentriq (atezolizumab)

over4years

Genetic characteristics of gastric-type mucinous carcinoma of the uterine cervix. (PubMed, Mod Pathol)

In addition, GAS shared some genetic features with gastrointestinal adenocarcinoma. These findings provide a clue in understanding the biological basis of GAS.

over 4 years ago

Journal • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • KMT2D (Lysine Methyltransferase 2D) • FGFR4 (Fibroblast growth factor receptor 4) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • EPCAM (Epithelial cell adhesion molecule) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)

TP53 mutation • KRAS mutation • STK11 mutation • CDKN2A mutation • KRAS mutation + STK11 mutation • RNF43 mutation • ERBB3 mutation • TP53 expression

over4years

Characteristics and outcomes of patients with metastatic KRAS mutant lung adenocarcinomas: The Lung Cancer Mutation Consortium experience. (PubMed, J Thorac Oncol)

In the LCMC study, 27% of lung adenocarcinomas patients harbored a KRAS mutation and up to third of them had another oncogenic driver. Patients with both KRAS and STK11 mutations had a significantly inferior clinical outcome.

over 4 years ago

Clinical • Journal

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)

KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • STK11 mutation • KRAS G12 • KRAS mutation + STK11 mutation

over4years

Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia. (PubMed, J Med Biochem)

Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease.

over 4 years ago

Clinical • Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • NOTCH1 (Notch 1)

KRAS mutation • PTEN mutation • STK11 mutation • KRAS mutation + STK11 mutation

over4years

Receptor Tyrosine Kinase Signaling Networks Define Sensitivity to ERBB Inhibition and Stratify Kras Mutant Lung Cancers. (PubMed, Mol Cancer Ther)

Interestingly, in human NSCLCs, phosphorylation of EGFR or ERBB3 was frequently detected in ASCs and squamous cell carcinomas. We conclude that analysis of in situ ERBB signaling networks in conjunction with ex vivo drug response profiling and biochemical dissection of adaptive RTK activities may serve as valid diagnostic approach to identify tumors sensitive to ERBB network inhibition.

over 4 years ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)

TP53 mutation • KRAS mutation • STK11 mutation • KRAS mutation + STK11 mutation

over4years

[VIRTUAL] Association of molecular heterogeneity and actionable mutations with survival in lung cancer (AACR-II 2020)

Our results showed an increased median overall survival in patients with lung adenocarcinoma that harbor actionable mutations compared to wild-type patients. Exploiting the appropriate use of clinical and genomic data collected and maintained in patient registries may better account for patient populations seen in the academic and community settings to improve cohort selection for clinical trials and survival outcomes.

over 4 years ago

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • LRP1B (LDL Receptor Related Protein 1B)

BRAF V600E • KRAS mutation • BRAF V600 • ALK rearrangement • STK11 mutation • KRAS mutation + STK11 mutation

over4years

[VIRTUAL] CDKN2A mutation predicts immunotherapy resistance in stage III/IV NSCLC (AACR-II 2020)

In a large cohort of stage III/IV NSCLC patients treated with systemic therapy and RT, NGS identified CDKN2A mutation/deletion as a predictor of ICB resistance and poor outcome. In the context of recent evidence for sensitivity to CDK4/6 inhibition of CDKN2A-deficient tumors, our findings raise the possibility of utilizing currently available targeted agents in the treatment of CDKN2A-deficient NSCLC patients progressing on ICB.

over 4 years ago

PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

TP53 mutation • KRAS mutation • STK11 mutation • CDKN2A deletion • CDKN2A mutation • KRAS mutation + STK11 mutation • CDKN2A negative • KRAS deletion • miR-138 underexpression + miR-497 overexpression

over4years

[VIRTUAL] Mutational landscape of STK11, PD-L1 expression, and TMB in patients with non-small cell lung cancer (AACR-II 2020)

The results showed that in our cohort, Chinese NSCLC patients with STK11 GAs were enriched in PD-L1-neg/TMB-H subgroup and associated with a poor response to ICIs in Chinese NSCLC patients. We also found that co-mutations of STK11 and KEAP1 may have implications as a negative biomarker for guiding ICI treatment.

over 4 years ago

Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)

PD-L1 expression • KRAS mutation • TMB-H • STK11 mutation • KEAP1 mutation • KRAS mutation + STK11 mutation • KEAP1 mutation + KRAS mutation

over4years

[VIRTUAL] Genomic alterations profiling by liquid biopsy and their association to immune checkpoints inhibitors (ICI) response in a cohort of non-small cell lung cancer (NSCLC) patients. (ASCO 2020)

"Our results support the idea that tumor alterations identified by liquid biopsy panels can potentially contribute as biomarkers of response to ICI in NSCLC. When analyzing the mutational panorama after ICI treatment, we find that those patients exhibiting KRAS and/or STK11 mutations in their ctDNA have a shorter PFS. Research Funding: None"

over 4 years ago

Clinical

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)

TP53 mutation • STK11 mutation • KRAS mutation + STK11 mutation

Guardant360® CDx

over4years

[VIRTUAL] Clinical characteristics and anti-PD-(L)1 treatment outcomes of KRAS-G12C mutant lung cancer compared to other molecular subtypes of KRAS-mutant lung cancer. (ASCO 2020)

"KRAS G12C mutations are present in 12% of patients with NSCLC and represent a relevant subtype of NSCLC given KRAS G12C inhibitors now in clinical development. Baseline characteristics including co-mutation patterns are similar between patients with G12C and non-G12C, except for smoking history. The efficacy of KRAS G12C direct inhibitors will need to be compared to other available therapies for KRAS mutant NSCLC (chemotherapy and PD-(L)1 inhibitors) to identify most effective therapeutic strategy."

over 4 years ago

Clinical

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)

KRAS G12C • KRAS G12V • STK11 mutation • KEAP1 mutation • KRAS G12A • KRAS G12 • KRAS mutation + STK11 mutation

MSK-IMPACT

over4years

[VIRTUAL] Long-term responders to PD-1 blockade in patients with advanced non-small cell lung cancer (NSCLC). (ASCO 2020)

"Long-term response (LTR, ongoing response ≥ 24 months) to PD-1 blockade is an uncommon but profound clinical outcome in metastatic lung cancers. Younger age and high TMB correlate with LTR; the combination of high TMB/high PD-L1 enriches for LTR but not STR. Features predicting long term response may be distinct from those predicting initial response."

over 4 years ago

Clinical

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • KEAP1 (Kelch Like ECH Associated Protein 1)

PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • PTEN mutation • ARID1A mutation • STK11 mutation • TMB-L • KEAP1 mutation • KRAS mutation + STK11 mutation

MSK-IMPACT