Phase 2 VISION Trial Shows Promise for Tepotinib in NSCLC

According to findings from the phase 2 VISION trial, which were simultaneously presented at the 2020 ASCO Virtual Scientific Program and published in the New England Journal of Medicine, tepotinib demonstrated durable clinical activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who harbor a MET exon 14 (METex14) skipping mutation identified through liquid or tissue biopsy.^1,2

METex14 skipping mutations occur in 3% to 4% of patients with NSCLC. The mutation generally occurs in older patients and is mutually exclusive with other frequently occurring genomic alterations in lung cancer.

“The results are massively positive,” lead study author, Xiuning Le, MD, PhD, of The University of Texas MD Anderson Cancer Center, said in an interview with our sister publication, OncLive. “Tepotinib is a promising targeted therapy with durable clinical activity and manageable toxicity in patients with METex14 skipping NSCLC, including patients with brain metastases.”

In the open-label, phase 2 study, patients with advanced or metastatic NSCLC with a conformed METex14 mutation were administered 500 mg of tepotinib once daily. The primary endpoint of the study was the objective response by independent review among patients who had undergone at least 9 months of follow-up. Response was also evaluated according to whether the presence of a MET exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy.

As of January 1, 2020, a total of 152 patients had received tepotinib and 99 had been followed for at least 9 months. At a minimum follow-up of 9 months, tepotinib led to an objective response rate (ORR) of 46.5% (95% CI, 36.4%-56.8%), as assessed by an independent review committee (IRC), and a median duration of response (DOR) of 11.1 months (95% CI, 7.2-not estimable [NE]). The disease control rate (DCR) was 65.7% (95% CI, 55.4%-74.9%).

Moreover, the response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was comparable regardless of the previous therapy received for advanced or metastatic disease.

Adverse events (AEs) of grade 3 or higher that investigators deemed to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Notably, AEs led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was also observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment.

“For targeted therapy to show this much definitive efficacy, we’re hopeful that we have enough evidence to convince the FDA to allow us to use tepotinib in patients with METex14 skipping mutations in the near future,” concluded Le.

In September 2019, the FDA granted a breakthrough therapy designation to tepotinib for the treatment of patients with metastatic NSCLC whose tumors harbor METex14 alterations and have progressed on prior platinum-based chemotherapy.³

References:

1. Le X, Felip E, Veillon R, et al. Primary efficacy and biomarker analyses from the VISON study of tepotinib in patients (pts) with non-small cell lung cancer (NSCLC) with METex14 skipping. J Clin Oncol. doi:10.1200/JCO.2020.38.

2. Paik PK, Felip E, Veillon R, et al. Tepotinib in non—small cell lung cancer with MET exon 14 skipping mutations. N Eng J Med. Published online May 29, 2020. doi:10.1056/NEJMoa2004407.

3. Merck KGaA, Darmstadt, Germany, announces FDA Breakthrough Therapy Designation for investigational therapy tepotinib in patients with metastatic NSCLC with METex14 skipping alterations. News release. Merck KGaA. Published September 11, 2019. Accessed May 31, 2020. https://prn.to/2kuDROO.