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Gene | KEAP1 |
Variant | mutant |
Impact List | unknown |
Protein Effect | unknown |
Gene Variant Descriptions | KEAP1 mutant indicates an unspecified mutation in the KEAP1 gene. |
Associated Drug Resistance | |
Category Variants Paths |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 |