News - KRAS mutation + STK11 mutation

almost2years

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

almost 2 years 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)

over2years

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 2 years 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

over2years

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 2 years ago

Review • Journal • IO biomarker • Metastases

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

KRAS mutation • STK11 mutation • KRAS mutation + STK11 mutation

over2years

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 2 years 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)

over2years

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 2 years 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

over2years

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 2 years 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)

almost3years

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 3 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

almost3years

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 3 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)

almost3years

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 3 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)

3years

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.

3 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

over3years

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 3 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

over3years

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 3 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