Hutchinson China Meditech Limited announces that The China National Medical Products Administration granted priority review to the new drug application for the MET inhibitor savolitinib for the treatment of patients with non–small cell lung cancer with MET exon 14 skipping mutations.
The China National Medical Products Administration has granted priority review to the new drug application for the MET inhibitor savolitinib for the treatment of patients with non–small cell lung cancer (NSCLC) with MET exon 14 skipping (METex14) mutations, according to an announcement from Hutchinson China Meditech Limited.1
Data from an open-label, phase 2 registration study (NCT02897479) with savolitinib were presented during the 2020 ASCO Virtual Scientific Program. In the study, savolitinib elicited encouraging antitumor activity and showed acceptable tolerability in patients with METex14-positive NSCLC.2
A total of 593 Chinese patients were screened, METex14 positivity was identified in 87 patients, and 70 patients were then treated with savolitinib. The majority of the patients included on the analysis were older, with median overall age of 68.7 years; 81.4% had an ECOG performance status of 1 and 24.3% of patients had brain metastases. Additionally, 92.9% of patients had stage IV disease and 60% of patients received previous systemic treatment. Of the 70 patients, 35.7% had pulmonary sarcomatoid carcinoma (PSC).
Results showed that savolitinib induced robust and durable tumor response in patients with METex14-positive NSCLC, with an objective response rate (ORR) of 49.2% per an independent review committee (IRC) assessment in the efficacy evaluable set and 42.9% in the full analysis set; this benefit was observed across patient subgroups. The duration of response was 9.6 months.
Although the progression-free survival (PFS) and overall survival (OS) data are not yet mature, the median PFS and OS was 6.9 months at 50.0% maturity and 14.0 months, at 45.7% maturity, respectively, in 70 patients. The PFS benefit was determined to be of clinical significance in the patients with PSC and other NSCLC subgroups, and encouraging benefit was observed in the subgroup of patients who received previous treatment.
With regard to safety, the median duration of treatment with savolitinib was 6.8 months, with 62 patients initially receiving 600 mg of the agent once daily, and 8 patients receiving 400 mg once daily. Eighteen patients (27.5%) experienced treatment-related serious adverse effects (SAEs), which included abnormal hepatic function (4.3%), hypersensitivity (2.9%), and pyrexia (2.9%). One patient had a treatment-related SAE, tumor lysis syndrome, which proved to be fatal.
Moreover, 14.3% of patients (n = 10) experienced treatment-related toxicities that resulted in treatment discontinuation; these effects included drug-induced liver injury and drug hypersensitivity (2.9%) and others.
Savolitinib is also under examination in the single-arm, open-label, phase 2 SAVANNAH trial (NCT03778229), which is examining the agent in combination with osimertinib (Tagrisso) in patients with EGFR-mutant, MET-driven, locally advanced or metastatic NSCLC following progression on osimertinib.3The primary end point of the trial is ORR and key secondary end points include ORR, PFS, mean change from baseline in EORTC QLQ-C30 and QLQ-LC13, plasma concentrations of osimertinib/savolitinib and metabolites, and total clearance of EGFR mutations at 6 weeks following treatment initiation, as well as safety.
Patients aged ≥18 years with histologically or cytologically locally confirmed advanced or metastatic EGFR-positive NSCLC harboring an EGFR mutation linked with EGFR TKI sensitivity, radiologic disease progression following treatment with osimertinib, MET-driven NSCLC confirmed via central fluorescence in situ hybridization, immunohistochemistry, or next-generation sequencing, at least 1 lesion not previously irradiated or biopsied during screening, and an ECOG performance status of 0 to 1 were eligible for enrollment.
Those who received previous treatment with a third-generation EGFR TKI beyond osimertinib, with savolitinib, or any other MET inhibitor were not permitted to enroll. Other exclusion criteria included those who received ≥4 prior lines of systemic treatment for their disease, more than 2 previous lines of EGFR TKI treatment, or >1 prior line of chemotherapy; those who received any anticancer therapeutics for advanced disease within 2 weeks before the first dose of the study treatment; if a PD-L1 inhibitor was received as their last previous treatment; and cardiac disease.
In the trial, patients with receive oral osimertinib at 80 mg once daily plus oral savolitinib at 300 mg once daily in a treatment period comprised of 28-day cycles. A RECIST v1.1 assessment will be given every 6 weeks for up to 24 weeks until disease progression. Safety follow-up will be done 28 days following treatment discontinuation and survival follow-up will be completed every 12 weeks. The first patient was enrolled on the trial on January 9, 2019.