On March 14, 2022, “Clinical Cancer Research”, a well-known international journal in the field of oncology, published the latest results of a subgroup of patients relevant to clinical practice in the VISION study, which mainly evaluated the effect of tepotinib on MET Efficacy and safety in patients with exon 14 skipping mutation non-small cell lung cancer (NSCLC).
Previously, on March 25, 2020, Merck KGaA announced that Japan the Ministry of Health, Labour and Welfare approved the marketing of Tepotinib for the treatment of unresectable, MET exon 14 Advanced or recurrent NSCLC patients with skipping mutations.
On February 3, 2021, the US Food and Drug Administration (FDA) granted accelerated approval to tepotinib for adult patients with metastatic NSCLC with MET exon 14 skipping.
On February 22, 2022, the European Union Commission approved tepotinib as a single agent for patients with NSCLC with MET exon 14 skipping mutations. These patients required systemic therapy following immunotherapy and/or platinum-based chemotherapy.
MET exon 14 (METex14) skipping mutations cause a particularly aggressive form of non-small cell lung cancer in patient populations, often elderly, who face poor clinical outcomes and urgent needs New treatment options.
Tepotinib is a highly selective, daily oral MET inhibitor that has shown promising clinical activity in the treatment of non-small cell lung cancer patients with MET exon 14 skipping mutations.
Trade Name: Tepmetko
Generic Name: Tepotinib p>
Target: MET
First approval in the US: February 2021
China First Approved: Not Approved
Approved Indication: For the treatment of unresectable, MET exon 14 skipping mutations in advanced or recurrent non-small cell lung cancer Cell lung cancer (NSCLC) patients
Recommended dose: 450 mg once daily orally; take with food.
Storage conditions: Room temperature 20°C-25°C
Clinical data
VISION (NCT02864992) is a Phase II , single-arm, multi-cohort, open-label trial, conducted at more than 130 sites in 14 countries, evaluating the antitumor activity and tolerability of tepotinib in advanced NSCLC harboring MET 14 skipping in cohorts A and C. Cohort A is the primary analysis set.
As of July 1, 2020, 152 patients in cohort A were analyzed as the effective population. In this population, the median treatment duration was 7.0 months, and the median follow-up duration was 16.4 months; 28 (18.4%) patients were still on treatment at the time of analysis. The population characteristics of these patients included a median age of 73.1 years, 52.0% of patients were male, and 52.0% of patients had a history of smoking.
The primary endpoint of the study was objective response rate (ORR) as judged by the Independent Review Committee (IRC) according to Response Evaluation Criteria in Solid Tumors (RECIST); secondary endpoints are investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
In the efficacy-evaluable population, the objective response rate (ORR) assessed by IRC according to RECIST criteria was 44.7% (68/152). Moreover, the onset of action was rapid, with 57 (83.8%) of 68 patients recording a response at the first (6 weeks) or second (12 weeks) tumor assessment. The median duration of response (DOR) was 11.1 months, and the median progression-free survival (PFS) was 8.9 months.
The investigator-assessed ORR was 53.3%, and the median DOR was 12.5 months. In addition, when the follow-up time was ≥9 months, the median overall survival (OS) was 17.6 months; the disease control rate (DCR) was 70.4%.
Since MET 14 skipping mutations frequently occur in older NSCLC patients, analyses were performed by age. By IRC assessment, the ORR was 48.8% for patients 75 years old and 39.7% for patients ≥75 years old. The ORR of patients ≥80 years old (n=37) was 35.1%, DCR was 67.6%, median DOR was 10.1 months, and median PFS was 8.6 months.
ORR by IRC was comparable regardless of treatment line, 44.9% in treatment-naïve patients and 44.6% in previously treated patients >. In addition, in treatment-naïve patients, the median DOR was 10.8 months, the median PFS was 8.5 months, and the DCR was 68.1%; in the previously treated patients, the median DOR was 11.1 months, and the median PFS was 10.9 months with a DCR of 72.3%.
In this study, there were 23 patients with brain metastases at baseline, 17 of whom had received radiotherapy. The results showed that the ORR was 47.8%, the median DOR was 9.5 months, and the median PFS was 9.5 months.
Adverse Reactions
Across all patients, the most common adverse reactions of any grade included: peripheral edema (54.1%), nausea
strong> (20%), diarrhea (19.6%), elevated serum creatinine (17.6%), hypoalbuminemia (14.5%) ), increased alanine aminotransferase (8.6%), decreased appetite (8.2%), increased amylase (7.5%), fatigue (7.1%), hair loss (7.1%), increased lipase (6.7%), Pleural effusion (6.3%), edema (6.3%), elevated aspartate aminotransferase (5.9%), constipation (5.9%), weakness (5.5%), vomiting (5.5%), epigastric pain ( 5.5%).
The most common grade 3-4 adverse reactions included: peripheral edema (7.5%), pleural effusion (3.1%), Increased lipase (2.7%), hypoproteinemia (2.4%), alanine aminotransferase increased (2%), amylase increased< /strong> (2%), increased aspartate aminotransferase (1.2%), nausea (0.4%), diarrhea (0.4%), increased serum creatinine (0.4%), decreased appetite (0.4%), Fatigue (0.4%), weakness (0.4%), vomiting (0.4%).
Conclusion
Tepotinib showed meaningful activity in subgroups with different age, previous treatment and brain metastases, and the safety was manageable.
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