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Profile Name KEAP1 loss
Gene Variant Detail

KEAP1 loss (loss of function)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KEAP1 inact mut gallbladder cancer resistant Fluorouracil Preclinical Actionable In a preclinical study, gallbladder cancer cells harboring KEAP inactivating mutations had increased NRF2 activation and demonstrated resistance to Adrucil (fluorouracil) in culture (PMID: 18692501). 18692501
KEAP1 mutant lung non-small cell carcinoma predicted - resistant Radiotherapy Clinical Study - Cohort Actionable In a clinical study, non-small cell lung cancer patients harboring KEAP1 or NFE2L2 mutations (n=9) demonstrated higher incidence of local recurrence at 30-months after radiotherapy (70% vs 18%, p<0.003) compared to KEAP1/NFE2L2 wild-type patients (n=33) (PMID: 27663899). 27663899
KEAP1 mutant lung squamous cell carcinoma predicted - sensitive Sapanisertib Case Reports/Case Series Actionable In a Phase II trial, Sapanisertib (MLN0128) treatment resulted in a disease control rate of 66% (2/3, 2 stable disease) in lung squamous cell carcinoma patients harboring KEAP1 mutations (J Clin Oncol 37, 2019 (suppl; abstr 9085)). detail...
KEAP1 mutant lung non-squamous non-small cell carcinoma predicted - sensitive Camrelizumab + Rivoceranib Phase Ib/II Emerging In a Phase Ib/II trial, non-squamous NSCLC patients harboring KEAP1 and/or STK11 mutations (n=14) demonstrated an improved 12-month survival rate (85.1% vs 53.1%; p=0.01), and a trend towards improved objective response rate (42.9% vs 28.1%; p=0.33), disease control rate (92.9% vs 65.6%, p=0.053), and median progression-free survival (9.4 vs 5.3 months; p=0.64) compared to wild-type KEAP1/STK11 patients (n=32) treated with Camrelizumab (SHR-1210) plus Rivoceranib (apatinib) (PMID: 33323401; NCT03083041). 33323401
KEAP1 mutant lung adenocarcinoma not predictive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring a KEAP1 mutation demonstrated a shorter progression free survival compared to patients with wild-type KEAP1 when treated with an unspecified PD-1 antibody, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
KEAP1 mutant lung adenocarcinoma not predictive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring a KEAP1 mutation demonstrated a shorter progression free survival compared to patients with wild-type KEAP1 when treated with an unspecified PD-L1 antibody, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
KEAP1 mutant lung adenocarcinoma sensitive Radiotherapy + Telaglenastat Preclinical - Cell culture Actionable In a preclinical study, Telaglenstat (CB-839) increased sensitivity of a non-small cell lung cancer cell line harboring a KEAP1 mutation to radiotherapy in culture (PMID: 33071215). 33071215
KEAP1 inact mut lung adenocarcinoma sensitive Carboplatin + MSU38225 Preclinical - Cell line xenograft Actionable In a preclinical study, MSU38225 and Paraplatin (carboplatin) combination treatment synergistically inhibited growth of a lung cancer cell line harboring a KEAP1 inactivating mutation in culture and slowed tumor growth in a cell line xenograft model compared to vehicle or Paraplatin (carboplatin) alone (PMID: 34158350). 34158350
KEAP1 inact mut lung adenocarcinoma sensitive MSU38225 Preclinical - Cell culture Actionable In a preclinical study, MSU38225 inhibited Nrf2 transcriptional activity and downstream pathway activation, increased Nrf2 degradation, and inhibited growth of lung cancer cells harboring a KEAP1 inactivating mutation in 2D and 3D culture (PMID: 34158350). 34158350
KEAP1 inact mut lung adenocarcinoma sensitive Fluorouracil + MSU38225 Preclinical - Cell culture Actionable In a preclinical study, MSU38225 and Adrucil (fluorouracil) combination treatment inhibited growth of a lung cancer cell line harboring a KEAP1 inactivating mutation in culture (PMID: 34158350). 34158350