Table 2. Key clinical studies on patients with advanced NSCLC.
BID: twice daily; CI: confidence interval; ECOG PS: Eastern Cooperative Oncology Group Performance Status; mDOR: median duration of response; MET: mesenchymal-epithelial transition; METex14: mesenchymal-epithelial transition exon 14; mPFS: median progression-free survival; NA: not available; NGS: next-generation sequencing; NSCLC: non-small cell lung cancer; OD: once daily; OS: overall survival; RR: response rate; RT-PCR: reverse transcription polymerase chain reaction
| Trial name/Phase/Trial design | Sample size (n)/Patient population | Drug/Dose | Main outcome measures | Adverse events | Clinical implications | ||
| RR (%)/mDOR (months) | mPFS (months) | mOS (months) | |||||
| VISION/Phase II/Prospective, open-label, multicenter, single-dose trial [55] | n = 169 Advanced NSCLC with METex14 skipping mutation (ECOG PS 0/1; 0–2 lines of prior therapy) | Tepotinib, 500 mg OD, 9-month cycle | RR: independent review: 46% (95% CI = 36 to 57); investigator assessment: 56% (95% CI = 45 to 66); liquid biopsy: 48% (95% CI = 36 to 61); tissue biopsy: 50% (95% CI = 37 to 63) mDOR: 11.1 months (combined biopsy group; [95% CI = 7.2 to not estimated]), 9.9 months (liquid biopsy group; [95% CI = 7.2 to not estimated]), and 15.7 months (tissue biopsy group; [95% CI = 9.7 to not estimated]) | 8.5 months (combined biopsy group; [95% CI = 6.7 to 11]), 8.5 months (liquid biopsy group; [95% CI = 5.1 to 11.0]), and 11.0 months (tissue biopsy group; [95% CI = 5.7 to 17.1]) | 17.1 months (95% CI = 12.0 to 26.8; immature data) | Grade 3 or >3 peripheral edema | The study established tepotinib as a therapeutic option for patients with advanced NSCLC and with a confirmed METex14 skipping mutation as tepotinib led to durable antitumor activity in these patients |
| GEOMETRY mono-1/Phase II/Multiple-cohort trial [54] | n = 364 Advanced NSCLC (stage IIIB/IV; ECOG PS 0/1; 0–2 lines of prior therapy) with either METex14 skipping mutation or MET amplification | Capmatinib, 400 mg BID, 21 days cycle | Overall response: first- or second-line therapy: 41% (95% CI = 29 to 53); treatment naïve: 68% (95% CI = 48 to 84) mDOR: first- or second-line therapy: 9.7 months (95% CI = 5.6 to 13.0); treatment naïve: 12.6 months (95% CI = 5.6 to not estimated) | First- or second-line therapy: 5.4 months (95% CI = 4.2 to 7.0); treatment naïve: 12.4 months (95% CI = 8.2 to not estimated) | NA | Grade 1-2 peripheral edema, nausea | The study emphasized the need for extensive molecular testing before first-line treatment decisions and concurrent testing with RT-PCR and NGS to detect METex14 alterations in conditions pertaining to limited tissue availability. Also, based on the efficacy and safety profile of capmatinib in this study, it can be considered a new treatment option in advanced NSCLC with METex14 skipping mutation |
| PROFILE 1001/Phase I/Ongoing, prospective, open-label, multicenter trial [58] | N = 69 METex14 mutated advanced NSCLC | Crizotinib 250 mg BID, 28 days cycle | Objective response rate: 32% (95% CI = 21 to 45) mDOR: 9.1 months (95% CI = 6.4 to 12.7) | 7.3 months (95% CI = 5.4 to 9.1) | 20.5 months (95% CI = 14.3 to 21.8) | Grade 1-2 edema, nausea, vomiting, vision disorder, diarrhea | The study underscores the need for MET-directed targeted therapy in patients harboring METex14 alterations |