On November 25, 2022, the journal Targeted Oncology reported the final analysis results of the Phase II INSIGHT clinical trial (NCT01982955), mainly evaluating the effectiveness and safety of tepotinib combined with gefitinib in patients with EGFR mutations in patients with non-small cell lung cancer (NSCLC). These patients produced MET-driven drug-resistant mutations for EGFR tyrosine kinase inhibitors (TKIs) .
Previously, on March 30, 2022, the Drug Review Center of the State Food and Drug Administration (CDE) had accepted the application for the launch of the new drug for tepotinib. Public information shows that tepotinib is an oral MET inhibitor. has been approved for marketing in Japan and the United States for to treat NSCLC patients carrying exon 14 jump mutations. In addition, studies have shown that terpotinib has clinically significant activity and lasting response in NSCLC patients with MET amplification, and that safety is controllable.
Trade name: Tepmetko
Generic name: Tepotinib (Tepotinib)
Target: METht
First approved in the United States: February,
First approved in the United States: February,
First approved: February, 2021 ml5 First approved in China: Not approved Approved Indications: is used to treat advanced or recurrent non-small cell lung cancer (NSCLC) patients with unresectable and MET exon 14 jump mutations Specifications: 250mg Recommended dosage: 4 450mg/day, once a day, taken orally; taken with food.
Storage conditions: Room temperature 20°C-25°C
Clinical data
INSIGHT is an open-label, randomized, multicenter Phase Ib/II clinical trial of terpotinib and gefitinib in locally advanced or metastatic NSCLC patients. The trial planned a subgroup analysis in advance to evaluate patients with MET amplification or MET high expression of [ immunohistochemistry (IHC)3+]. These patients had EGFR mutations, were negative for T790M, were acquired resistance to first- or second-generation EGFR TKI treatments, and had an ECOG score of 0 or 1. All enrolled patients were randomly assigned to receive 500 mg of terpotinib combined with 250 mg of gefitinib (n=31) or chemotherapy (n=24).
Among these enrolled patients, 58% of the patients had previously used gefitinib, 21% of the patients had previously used afatinib , 11% of the patients had previously used erlotinib, and 11% of the patients had previously used eketinib . The median duration of previous EGFR-TKI treatment in tepotinib combined with gefitinib vs. chemotherapy group was 10.6 months vs. 9.5 months.
primary endpoint of this trial was the progression-free survival (PFS) evaluated by the researchers; secondary endpoint includes survival (OS), objective response rate (ORR), duration of response (DOR), PFS of the Independent Review Committee (IRC) and security. 19 patients in the trial had MET amplification. The median follow-up time for the final analysis of
was 57.5 months. At this time, the median treatment time for patients with tepotinib and gefitinib was 11.3 months, of which 13 patients with html received treatment for more than 4 years .
According to the latest research results, in patients with MET amplified , the median progression-free survival (PFS) of tepotinib combined with gefitinib vs chemotherapy group was 16.6 months VS 4.2 months ; the median survival (OS) was 37.3 months VS 13.1 months . In addition, the objective response rate (ORR) evaluated by the investigator was 66.7% VS 42.9% ; the ORR evaluated by the Independent Review Committee (IRC) was 75% VS 42.9% .
In 34 patients with MET high expression of , the median PFS of tepotinib combined with gefitinib vs chemotherapy group was 8.3 months VS 4.4 months ; the median OS was 29.1 months VS 17.9 months .
In the overall population of (n=55), the median PFS of tepotinib combined with gefitinib vs chemotherapy group was 4.9 months vs 4.4 months ; the median OS was 17.3 months vs 19.5 months .
Safety
All patients reported treatment-related adverse events (TRAEs). There were 7 cases in the combined group (58.3%) and 5 cases in the chemotherapy group (71.4%) with adverse reactions of grade 3 or above. The most common adverse reactions in the treatment group of
terpotinib combined with gefitinib include: diarrhea (50%), amylase (41.7%), lipase (41.7%), alanine transaminase (33.3%) and peripheral edema (33.3%).
In the chemotherapy group, the most common adverse reactions include: leukopenia (57.1%), neutropenia (57.1%), anemia (42.9%) and nausea (42.9%).
Summary
The latest results of this trial show that in patients with acquired resistant EGFR mutant NSCLC with MET amplification and MET high expression, both tepotinib combined with gefitinib had significant improvements in PFS and OS compared with chemotherapy.
Reference source:
https://www.targetedonc.com
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