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Tepotinib VISION, INSIGHT Trial Results Reported

Tepotinib shows promise for non-small-cell lung cancer patients who have MET-positive disease resistant to EGFR-TKI therapy or METex14 skipping alterations
29 Nov 2019
Anticancer Agents;  Basic Scientific Principles;  Clinical Research;  Non-Small Cell Lung Cancer;  Therapy

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Data for the VISION and INSIGHT clinical trials of the highly selective MET inhibitor tepotinib in patients with non-small-cell lung cancer (NSCLC) have been presented at the ESMO Asia Congress 2019 in Singapore. 

Niels Reinmuth, from Asklepios Lung Clinic in Munich-Gauting, Germany, presented interim findings for cohort A of the phase II VISION study of tepotinib 500 mg/day in patients with stage IIIB/IV NSCLC with METex14 skipping alterations detected by liquid or tissue biopsy. 

The 87 patients had received no (37.9%), one (35.6%), two (23.0%) or three (3.4%) prior lines of treatment including cytotoxic, immunotherapy or other regimens, 16.1% of whom had achieved a complete or partial response. 

Independent review committee (IRC) findings suggested that 90.4% of patients experienced some tumour shrinkage. The objective response rate (ORR) was 50.0% for the 48 patients positive for METex14 skipping by liquid biopsy and 45.1% for those positive on a tissue biopsy, giving a combined ORR of 43.8%. The mediation duration of response was 12.4, 15.7 and 15.7 months, respectively, with corresponding 12-month event-free survival rates of 58%, 70% and 62%. 

Of note, the combined ORR was 50.0% for patients who received first-line tepotinib, falling to 40.4% for those who had received at least one earlier treatment. And similar activity was found when separately assessing a subgroup of 14 Japanese patients. 

“Responses occurred early and were durable across treatment lines”, said Neils Reinmuth, with treatment ongoing in 54% of patients at time of data analysis. Median progression-free survival (PFS) was 9.5 months. 

There were no grade 4 or 5 treatment-related adverse events (TRAEs), with all-grade events including peripheral oedema (48.3%), nausea (23.0%) and diarrhoea (20.7%). Among the subgroup of patients from Japan, the most common events were peripheral oedema and elevated creatinine (35.7% each) and diarrhoea (28.6%). 

“The VISION study is ongoing and includes a cohort of patients with high MET amplification (Cohort B) and a new cohort of patients with METex14 skipping alterations (Cohort C)”, the presenter concluded, noting that tepotinib has now been granted fast-track designation for patients with METex14 skipping alterations in both the USA and Japan. 

Long-term results for the INSIGHT trial of patients with EGFR-mutated NSCLC were also presented at the congress, by Ross Soo, from National University Cancer Institute in Singapore. 

Following “promising activity” for tepotinib in patients with MET-positive NSCLC who had acquired resistance to gefitinib treatment in phase Ib of the trial, the phase II part of the study included patients who were resistant to EGFR–TKI therapy but did not have the T790M mutation. 

Patients were randomly assigned to receive tepotinib 500 mg/day plus gefitinib 250 mg/day or a regimen of pemetrexed with cisplatin or carboplatin. 

Initial results indicated improved PFS and overall survival (OS) for tepotinib–gefitinib versus chemotherapy, especially in those who had MET amplification or strong positivity for MET on immuohistochemistry. 

Now, Ross Soo reported 18-month OS and PFS results for the patients with MET amplification, defined as in situ hybridisation gene copy number of at least 5 and/or a MET copy number to chromosome 7 centromere ratio of 2 or more. 

Median PFS by IRC assessment was 19.3 months with tepotinib–gefitinib versus 5.5 months with chemotherapy, with a significant hazard ratio (HR) for progression or death of 0.18, while median OS in the arms was 37.3 versus 13.1 months and a significant HR for death of 0.08. 

“MET amplification can be considered to be a suitable biomarker for treatment with tepotinib”, the investigator commented. 

Patients continued with tepotinib–gefitinib for a median of 49.1 weeks but TRAEs were “mostly mild to moderate with few dose reductions or discontinuations”, he said. By comparison, the chemotherapy components were used for between 5.9 and 12.0 weeks and grade 3 and more severe events occurred in 71.4% of this group versus 58.3% of the patients using tepotinib–gefitinib. 

Use of tepotinib in combination with osimertinib will now be assessed in the INSIGHT 2 trial of patients with EGFR-mutant NSCLC with acquired resistance to first-, second, or third-generation EGFR–TKI therapy related to MET amplification, Ross Soo concluded. 

 

References 

  • Park K, Felip E, Veillon R, et al. Tepotinib in NSCLC patients harboring METex14 skipping. Cohort A of phase II VISION study. Ann Oncol 2019; 30 (suppl_9): ix22–ix29. 10.1093/annonc/mdz420
  • Park K, Zhou J, Kim D-W, et al. Tepotinib plus gefitinib in patients with MET-amplified EGFR-mutant NSCLC. Long-term outcomes of the INSIGHT study. Ann Oncol 2019; 30 (suppl_9): ix157–ix181. doi: 10.1093/annonc/mdz437
Last update: 29 Nov 2019

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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