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Introduction: In the primary analysis of VISION, tepotinib — a highly selective, potent MET inhibitor — demonstrated durable efficacy, and a tolerable safety profile in patients (pts) with METex14 skipping NSCLC. We report updated outcomes, with interim analyses from a confirmatory cohort. Methods: In the Phase II VISION study, pts with advanced/metastatic METex14 skipping NSCLC, identified by liquid (L+) and/or tissue (T+) biopsy, received 500 mg (450 mg active moiety) tepotinib once daily. All pts were assessed for safety; pts with ≥3 months’ follow-up were assessed for efficacy. Primary endpoint was objective response by independent review (RECIST v1.1). Secondary endpoints were disease control (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of Feb 1, 2021, 7,882 pts were pre-screened, and 275 pts were analyzed for efficacy. Patients analyzed for efficacy had a median age of 72.4 years (range, 41-94]), 50.9% were female, 46.5% had smoking history, and median tumor load [target lesions by IRC] was 57.4 mm [range, 10.2-227.8]). Tumor load in L+ pts was 68.0 mm (11.6-227.8) and 52.9 mm (10.2-227.8) in T+ pts. In treatment-naïve pts (n=137), ORR was 54.0% (95% CI: 45.3, 62.6), DCR was 74.5% (66.3, 81.5), and >90% of pts had tumor shrinkage. Median (m) DOR was 32.7 months (9.0, not estimable), mPFS was 10.4 months (8.4, 15.3), and mOS was 17.6 months (13.4, 29.7). In previously treated pts (n=138), ORR was 44.2% (35.8, 52.9), DCR was 75.4% (67.3, 82.3), and >90% of pts had tumor shrinkage. mDOR was 11.1 months (8.4, 18.5), mPFS was 11.0 months (8.2, 12.4), and mOS was 19.9 months (15.8, 22.3). Meaningful clinical activity was observed in L+ and T+ pts (Table). Overall, 14.1% of pts discontinued due to TRAEs; tepotinib was well-tolerated across treatment lines (Table). Conclusions: Tepotinib demonstrated robust and durable clinical activity across treatment lines in pts with METex14 skipping NSCLC, with particularly durable efficacy in first line. TRAEs were manageable with few discontinuations. Table 1. Tepotinib efficacy and safety in patients with METex14 skipping NSCLC (VISION) Tepotinib efficacy (pts with ≥3 months’ follow-up in Cohorts A+C) Overall Treatment-naϊve (n=137) Previously treated (n=138) Combined (N=275) Liquid biopsy* (n=81) Tissue biopsy* (n=86) Liquid biopsy* (n=78) Tissue biopsy* (n=88) Objective response rate, % (95% CI) 49.1 (43.0, 55.2) 54.3 (42.9, 65.4) 54.7 (43.5, 65.4) 43.6 (32.4, 55.3) 47.7 (37.0, 58.6) Disease control rate, % (95% CI) 74.9 (69.4, 79.9) 71.6 (60.5, 81.1) 80.2 (70.2, 88.0) 69.2 (57.8, 79.2) 79.5 (69.6, 87.4) Median duration of response, months (95% CI) 13.8 (9.9, 19.4) 13.8 (7.2, ne) 32.7 (10.8, 32.7) 11.1 (8.4, 19.4) 10.1 (8.3, 15.7) Median progression-free survival, months (95% CI) 10.8 (8.5, 12.4) 8.5 (6.9, 11.3) 15.3 (9.6, ne) 8.3 (5.7, 11.0) 11.1 (8.2, 16.8) Median overall survival, months (95% CI) 19.7 (15.6, 22.1) 15.1 (9.5, 22.1) 29.7 (15.3, ne) 19.9 (12.8, 22.3) 22.3 (17.0, 27.2) Tepotinib safety (all pts who received tepotinib in Cohorts A+C) Overall (N=291) Treatment-naϊve (n=148) Previously treated (n=143) Treatment-related AEs†, n (%) Any grade 264 (90.7) 137 (92.6) 127 (88.8) Grade ≥3 86 (29.6) 49 (33.1) 37 (25.9) Leading to death 2 (0.7) 1 (0.7) 1 (0.7) Leading to a dose reduction 90 (30.9) 51 (34.5) 39 (27.3) Leading to temporary discontinuation 114 (39.2) 63 (42.6) 51 (35.7) Leading to permanent discontinuation 41 (14.1) 24 (16.2) 17 (11.9) All-cause AEs† in ≥20% of patients, n (%) Peripheral edema 191 (65.6) 98 (66.2) 93 (65.0) Nausea 88 (30.2) 51 (34.5) 37 (25.9) Diarrhea 81 (27.8) 42 (28.4) 39 (27.3) Hypoalbuminemia 81 (27.8) 41 (27.7) 40 (28.0) Blood creatinine increase 76 (26.1) 34 (23.0) 42 (29.4) Dyspnea 60 (20.6) 40 (27.0) 20 (14.0) Data cut-off: Feb 1, 2021. *Patients with METex14 skipping detected by both liquid and tissue biopsy are included in both analysis sets (overall, n=59; treatment-naïve, n=30; previously treated, n=29); testing by both methods was not required for enrollment. †AEs were defined as events that started within the day of first dose of trial treatment until 30 days after last dose of treatment or started prior to first dose but worsened during the treatment period. AEs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. AE, adverse event; CI, confidence interval; MET, mesenchymal-epithelial transition factor; METex14; MET exon 14; ne, not estimable. Citation Format: Marina C. Garassino, Xiuning Le, Wade T. Iam, Enriqueta Felip, Hiroshi Sakai, Remi Veillon, Egbert F. Smit, Julien Mazieres, Jo Raskin, Alexis B. Cortot, Karin Berghoff, Rolf Bruns, Gordon Otto, Paul K. Paik. Tepotinib efficacy and safety in patients with MET exon 14 (METex14) skipping NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT536. |
