Dr. Paul K. Paik, MD, on the Phase II study of Tepotinib.
Background: MET exon 14 skipping (METex14) mutations – reported in 3~4% of NSCLC patients (pts) – are activating, sensitive to MET inhibition and can be conveniently detected using liquid biopsy (LBx). We report data from an ongoing single-arm phase II study of tepotinib, a highly selective MET inhibitor, in NSCLC pts with METex14 mutations identified by LBx or tumor biopsy (TBx) (NCT02864992). Methods: Pts with advanced WT EGFR/ALK NSCLC, prospectively enrolled via either LBx (?60 pts) or TBx (?60 pts, overlap anticipated) central RNA-based METex14 mutation testing, receive tepotinib 500 mg QD until progression, intolerable toxicity or withdrawal. Primary endpoint: objective response rate (ORR) by independent review (IRC). Secondary endpoints: ORR by investigator assessment (INV) and safety. Results: To date, 85 pts have been enrolled (55 LBx pts and 52 TBx pts). At data cut-off (16 Oct 2018), in 35 evaluable LBx pts (?2 post-baseline assessments or discontinuation for any reason), ORR was 51.4% by IRC and 63.9% by INV. In 41 evaluable TBx pts, ORR was 41.5% by IRC and 58.5% by INV. Median duration of response (mDoR) and ORR by line of treatment are shown in the table. Any grade treatment-related adverse events (TRAEs) reported by ?10% of 69 pts evaluable for safety were peripheral edema (47.8%), diarrhea (18.8%), nausea (15.9%), asthenia (10.1%). No TRAEs were grade 4 or led to death. TRAEs led to permanent discontinuation in 2 (2.9%) pts (1 ILD, 1 diarrhea & nausea). Conclusions: Tepotinib has promising activity with a long DoR across treatment lines in NSCLC pts with METex14 mutations detected by LBx or TBx. The safety profile was favorable. Recruitment is ongoing.