HS-10241

P3, N=314, Not yet recruiting, Jiangsu Hansoh Pharmaceutical Co., Ltd.

The prevalence rate of coexisting MET exon 14 mutations and EGFR sensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2%,and the management of these subtype is not identified.This patient has received significant clinical benefits from antivascular drugs combined with chemotherapy sequential third generation EGFR-TKI Aumolertinib therapy, especially the sustained remission of intracranial lesions, which provides a reference for our clinical treatment of such patients. Case presentation. In November 2021,a 47-year-old male patient developed head discomfort with left lower limb weakness for 1 week.Brain MRI showed multiple intracranial lesions, which were considered to be brain metastases.In order to identify the primary lesion,CT showed a soft tissue mass in upper lobe of the right lung and mediastinal lymphadenopathy.To determine the pathological type,In December 2021,he underwent a lung biopsy, whose path report showed lung adenocarcinoma.The patient was diagnosed with right lung adenocarcinoma(T1N2M1,IV),accompanied by mediastinal lymph nodes and brain metastases.In an effort to control the symptoms of central nervous system(CNS) more quickly,bevacizumab combined with PC regimen was administered before genetic testing results are available.After 2 cycles of treatment,the lung and intracranial masses achieved a partial response(PR).Subsequently, polymerase chain reaction (PCR) detection revealed the simultaneous presence of EGFR exon 21 L858R and MET exon14 skipping mutations.Due to the lack of effective treatment method(Currently, there is insufficient evidence to support the therapy strategies of combining EGFR-TKI and MET inhibitor in such patients), aumolertinib, the third-generation EGFR-TKI approved in China 2020, was monotherapy given 110 mg per day orally.The reexamination found that the lung and intracranial masses of the patient were further narrowing and maintained PR, and the metastatic lesions in the left frontal lobe were also shrank,while the enhancement lesion disappeared.Up to now, this patient has achieved a PFS of more than 14 months.Of note,there were no significant drug-related adverse events during the treatment period,and he is still under a close follow-up. In this case, we reported a NSCLC patient with EGFR-sensitive combining MET Exon 14 Skipping mutations, who obtained a remarkable curative effect after aumolertinib, especially the CNS lesions have been continuously relieved. In this case, we reported a NSCLC patient with EGFR-sensitive combining MET Exon 14 Skipping mutations, who obtained a remarkable curative effect after aumolertinib, especially the CNS lesions have been continuously relieved. This was the first report applied aumolertinib to patients with EGFR and MET co-mutations, which providing us with a reference for treatment of such patients. Currently, phase Ib clinical trial of aumolertinib combined with c-MET inhibitor(HS-10241) are being conducted in patients with advanced NSCLC(NCT05430386), and will provide a promising treatment plan for the survival of such patients in the future.

HS-10241 in combination with almonertinib was well tolerated, and showed encouraging antitumor activity in treatment of advanced NSCLC with EGFR mutation and MET amplification following prior EGFR-TKI, whether MET GCN ≥10 or MET GCN ≥5 but < 10. Clinical trial information: NCT05430386.

P1, N=174, Recruiting, Jiangsu Hansoh Pharmaceutical Co., Ltd.