24P Tepotinib in patients with MET exon 14 skipping NSCLC: Efficacy and safety by line of therapy

Abstract

We report outcomes for tepotinib – a highly selective, potent MET inhibitor – in patients (pts) with MET exon 14 (METex14) skipping in VISION Cohorts A (primary analysis) and C (confirmatory), by prior therapies. These are relevant for clinical practice, given the CHMP positive opinion (Dec 2021) for tepotinib in patients with advanced NSCLC harboring METex14 skipping, previously treated with immunotherapy (IO) and/or platinum-based chemotherapy (CT). Pts with advanced/metastatic METex14 skipping NSCLC received 500 mg (450 mg active moiety) tepotinib once daily. Safety was assessed in all pts who received tepotinib, and efficacy in pts with ≥3 months’ follow-up (data cut-off: Feb 1, 2021). Primary endpoint was objective response by IRC (RECIST 1.1). Of 275 pts evaluable for efficacy, 138 were previously treated (+2L): median age 70.9 years (range, 41–89), 51% female, 40% smoking history, 42.0% enrolled in Europe. 86% of +2L pts had prior platinum-based CT, 53% had prior IO (37% as monotherapy, 15% had IO-CT). Objective response rate (ORR) was 44.2% (95% CI: 35.8, 52.9), with median duration of response (mDOR) of 11.1 (8.4, 18.5). Disease control rate was 75.4% (67.3, 82.3), and median overall survival (mOS) was 19.9 months (15.8, 22.3). Efficacy was observed regardless of prior therapies (Table). 137 pts were treatment-naïve (1L): median age 74.6 years (range, 47–94), 50% female, 53% smoking history, 60.6% enrolled in Europe. ORR was 54.0% (45.3, 62.6) and mOS was 17.6 months (13.4, 29.7). Overall, pts with brain metastases at baseline (51/275 [18.5%]) had systemic ORR of 52.9% (38.5, 67.1), and mDOR of 9.0 months (5.6, ne). Treatment-related adverse events (TRAEs) were mostly mild-moderate across therapy lines; Grade ≥3 TRAEs occurred in 33.1% of 1L pts and 25.9% +2L pts. Safety profile was similar in pts with prior IO.Table: 24PTepotinib efficacyORR, % (95% CI)Median duration of response, months (95% CI)Median progression-free survival, months (95% CI)Line of therapy1L (n=137)54.0 (45.3, 62.6)32.7 (9.0, ne)10.4 (8.4, 15.3)+2L (n=138)44.2 (35.8, 52.9)11.1 (8.4, 18.5)11.0 (8.2, 12.4)2L (n=88)44.3 (33.7, 55.3)12.4 (8.3, ne)8.9 (6.9, 13.7)+3L (n=50)44.0 (30.0, 58.7)10.1 (6.9, 19.4)11.2 (6.9, 13.8)Prior therapiesPlatinum-based CT alone (n=98)48.0 (37.8, 58.3)12.4 (8.3, 18.5)11.0 (6.9, 13.7)IO monotherapy or IO + platinum-based CT (n=71)38.0 (26.8, 50.3)9.7 (8.3, ne)10.9 (6.9, 12.1)IO + platinum-based CT (n=21)52.4 (29.8, 74.3)9.5 (4.2, ne)10.9 (5.5, ne)CI, confidence interval; L, line; ne, not estimable. Open table in a new tab CI, confidence interval; L, line; ne, not estimable. Tepotinib demonstrated robust and durable clinical activity across treatment lines, and in pts with brain metastases. TRAEs were mostly mild-moderate.