TAS-121 / Otsuka - LARVOL DELTA

HSP90 inhibition overcomes EGFR amplification-induced resistance to third-generation EGFR-TKIs. (PubMed, Thorac Cancer) - "EGFR amplification confers resistance to third-generation EGFR-TKIs which can be overcome by HSP90 inhibition. The results provide a preclinical rationale for the use of HSP90 inhibitors to overcome EGFR amplification-mediated resistance."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HSP90AA1

EGFR Amplification Mediates Resistance to TAS121, A Third-Generation EGFR-TKI, in EGFR T790M-Positive Non-Small Cell Lung Cancer (WCLC 2017) - "...A 68-year-old woman with metastatic lung adenocarcinoma, harboring an EGFR L858R mutation, received gefitinib in September 2013. Although the patient achieved a partial response, the tumor progressed and she was treated with 4 cycles of chemotherapy using cisplatin and pemetrexed followed by pemetrexed maintenance therapy...Tumor progression was noted after completion of one cycle of docetaxel, and she was enrolled into a phase 1 trial of TAS121 in June 2015...Our case revealed that genomic instability of the EGFR domain contributed to the development of resistance to TAS121. Further molecular analysis is warranted to understand the role of EGFR amplification in acquired resistance to third-generation EGFR-TKIs."

Biomarker • Clinical • Next-Generation Sequencing • Hepatocellular Cancer • Non Small Cell Lung Cancer

Phase I study of TAS-121, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with non-small-cell lung cancer harboring EGFR mutations. (PubMed, Invest New Drugs) - "Conclusions TAS-121 was well tolerated up to the MTD and demonstrated antitumor activity in Japanese T790M-positive NSCLC patients. Clinical trial registration: JapicCTI-142651."

Clinical • Journal • P1 data

TAS-121, a selective mutant EGFR inhibitor, shows activity against tumors expressing various EGFR mutations including T790M and uncommon mutations G719X. (PubMed, Mol Cancer Ther) - "TAS-121 potently inhibited common activating and resistance EGFR mutations to the same extent as another third-generation EGFR-TKI (osimertinib). Moreover, TAS-121 displayed antitumor activity in SW48 (EGFR G719S) and NCI-H1975 (EGFR L858R/T790M) xenograft models, and achieved an objective response in NSCLC patients with EGFR mutations including G719A mutation. In conclusion, TAS-121 is a novel third-generation EGFR-TKI and demonstrates anti-tumor activities in patients with NSCLC expressing either common or uncommon EGFR mutations."

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