New Targeted Therapies Show Promise for METex14-Altered NSCLC

Silas Inman @silasinman
Published: Monday, Jun 03, 2019

The VISION study consisted of 2 cohorts: cohort A enrolled patients with METex14 skipping mutations and cohort B included those with MET amplification. In both groups, tepotinib was administered at 500 mg once daily in a 21-day cycle. In cohort A, 87 patients were enrolled and treated, with METex14 determined using liquid (n = 57) and tumor biopsy (n = 58).

The median age of patients was 74 years, and the most common ECOG status was 1 (74.7%). Brain metastases were present in 9.2% of patients. Overall, 33 patients were treatment-naive, and 54 were treated in the second-line or beyond.

Across all lines of treatment, the ORR by IR in liquid biopsy-identified METex14-positive tumors was 50%. The median DOR was 12.4 months and the DCR was 66.7%. For those identified by tissue biopsy, the ORR was 45.1% and the median DOR was 15.7 months with a DCR of 72.5%.

By line of therapy, the ORR by IR was 58.8% in the first-line and 53.3% in the second-line in the liquid biopsy-identified patients. In the second-line and beyond, the ORR by IR was 45.2%. For those with tissue biopsy assessed tumors, the ORR by IR was 44.4% and 50%, in the first- and second-line, respectively. In the second-line or greater, the ORR by IR was 45.5%.

“Tepotinib has shown durable clinical activity in patients with NSCLC harboring METex14 mutations, detected by liquid biopsy or tissue biopsy,” said lead investigator Paul K. Paik, MD, from the Memorial Sloan Kettering Cancer Center. “Promising and consistent activity was observed across treatment lines, and patients with brain metastases at baseline benefitted equally from treatment.”

Across all treatment lines, median PFS was 9.5 months by IR in liquid biopsy assessed tumors and was 10.8 months in tumor biopsy-identified tumors. The median duration of response across arms was 14.3 months.

There were no grade 4 or 5 treatment-related AEs with 500 mg tepotinib. The most common treatment-related AEs were peripheral edema (48.3%), nausea (23.0%), diarrhea (20.7%), and blood creatinine increase (12.6%), although there were no signs of kidney impairment, Paik noted. The only commonly occurring grade 3 treatment-related AE was peripheral edema, which occurred in 8% of patients.

Future Developments

The FDA has granted designations to help speed up the development of both agents, based on the early promise. Capmatinib has received an orphan drug designation and a breakthrough therapy designation for METex14 skipping mutation positive metastatic NSCLC following platinum-based chemotherapy. Tepotinib holds a fast track designation for advanced METex14-mutated NSCLC.

As these therapies move toward the clinic, it emphasizes the need to make NGS a standard of care for patients with NSCLC, Reckamp noted. “If patients aren't being tested for these alterations, then they aren't being treated,” she said. “We're at the frontier of liquid biopsies. They're here, and they're here to stay. Upfront NGS testing is actually more cost effective than sequential testing, exclusionary testing, and hot spot panel testing.”


  1. Wolf J, Setons T, Han J-Y, et al. Capmatinib (INC280) in METΔex14-mutated advanced non-small cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 study. J Clin Oncol. 2019;37 (suppl; abstr 9004).
  2. Pain PK, Veillon R, Cortot AB, et al. Phase II study of tepotinib in NSCLC patients with METex14 mutations. J Clin Oncol. 2019;37 (suppl; abstr 9005).
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