P45.03 Tepotinib in Patients with MET exon 14 (METex14) Skipping NSCLC as Identified by Liquid (LBx) or Tissue (TBx) biopsy

Abstract

METex14 skipping, an oncogenic driver occurring in 3–4% of NSCLC, can be detected by DNA- (NGS, Sanger sequencing) and RNA- (NGS, quantitative PCR assays) based methods using LBx or TBx samples. We investigated patient demographics and tepotinib efficacy according to the method of METex14 skipping detection. In the Phase II VISION study, patients with METex14 skipping advanced NSCLC, detected by LBx and/or TBx, received 500 mg (450 mg active moiety) tepotinib once daily. Primary endpoint was objective response by independent review committee using RECIST 1.1. Secondary endpoints included duration of response (DOR), and progression-free survival (PFS). Analysis in patients enrolled by LBx (L+) or TBx (T+) biopsy was predefined. As of July 1, 2020, 7,673 patients had been pre-screened; 264/6,798 were positive by LBx, and 223/2,184 by TBx, for METex14 skipping (1.0% of LBx and 31.5% of TBx samples were not evaluable/analyzed). Subsequently, 99 L+ and 88 T+ patients were enrolled in Cohort A (Table; 36 patients were L+/ T+). LBx may have been used in patients with higher tumor burden, and those not suitable for TBx. Median treatment duration (range) was 6.9 months (0.7–43.3) in L+ patients (n=18 with treatment ongoing), and 7.0 (<0.1–43.3) in T+ patients (n=16 ongoing). Objective response rate (ORR) in L+ patients was 47.5% (95% CI: 37.3, 57.8), median (m) DOR was 10.8 months (7.6, 18.5), and mPFS was 8.5 months (6.7, 10.9). In T+ patients, ORR was 45.5% (34.8, 56.4), mDOR was 12.4 months (9.9, not estimable), and mPFS was 11.0 months (8.2, 13.7). Tumor shrinkage was observed in 87.9% of L+, and 89.8% of T+ patients (Figure).Tabled 1Patients enrolled by liquid biopsy* (n=99)Patients enrolled by tissue biopsy† (n=88)Negative tissue biopsy result, n (%)5 (5.1)-Negative liquid biopsy result, n (%)-44 (50.0)Median age, years (range)72.4 (49–88)73.1 (41–94)Sex, n (%)Male52 (52.5)49 (55.7)Female47 (47.5)39 (44.3)RegionNorth America28 (28.3)24 (27.3)Europe51 (51.5)41 (46.6)Asia20 (20.2)23 (26.1)History of smoking, n (%)Yes51 (51.5)44 (50.0)No44 (44.4)36 (40.9)Missing4 (4.0)8 (9.1)ECOG performance status, n (%)023 (23.2)28 (31.8)176 (76.8)60 (68.2)Histological subtype, n (%)Adenocarcinoma84 (84.8)80 (90.9)Squamous10 (10.1)7 (8.0)Sarcomatoid3 (3.0)0Other2 (2.0)1 (1.1)Line of therapyTreatment-naïve44 (44.4)42 (47.7)Previously treated55 (55.6)46 (52.3)≥3 lesions, n (%)Target28 (28.3)14 (15.9)Non-target50 (50.5)30 (34.1)Median tumor load of target lesions, mm (range)64.5 (14.3–224.2)53.4 (10.2–180.2)Median time since initial cancer diagnosis, years (range)0.4 (<0.1–4.4)0.7 (<0.1–25.3)*DNA-based Guardant Health 360 assay; †RNA-based Oncomine Focus assay. ECOG, Eastern Cooperative Oncology Group. Open table in a new tab *DNA-based Guardant Health 360 assay; †RNA-based Oncomine Focus assay. ECOG, Eastern Cooperative Oncology Group. Tepotinib demonstrated durable clinical activity in patients with METex14 skipping NSCLC, as detected by LBx or TBx. These complementary testing methods led to similar efficacy with tepotinib in the VISION study.