Merck KGaA · XETR:MRK
Merck KGaA — Technical Presentation
13 slides from Merck KGaA's technical presentation
Slide 1: Tepotinib in Patients with Advanced NSCLC Harboring MET Exon 14-Skipping Mutations: Phase II Trial
Tepotinib in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring MET Exon 14-Skipping Mutations: Phase II Trial E. Felip1, L. Horn2, J.D. Patel3, H. Sakai4, J. Scheele5, R. Bruns5, P.K. Paik6, on behalf of the VISION Study Group 1Oncology Department, Vall d’Hebron University Hospital
Slide 2: Introduction
Introduction • ~3% of NSCLCs harbor mutations of the MET proto-oncogene that cause exon 14 to be skipped during mRNA processing (METexon14)1,2 • Exon 14 encodes the juxta membrane domain of MET, which plays an important role in ubiquitin-mediated MET degradation following activation by hepatocyte gr
Slide 3: VISION: A Phase II, Single-arm Trial of Tepotinib in Advanced NSCLC
VISION: A Phase II, Single-arm Trial to Investigate Tepotinib in Advanced NSCLC With METexon14-Skipping Alterations • Advanced/metastatic NSCLC Primary endpoint • all histologies Objective response rate • METexon14-skipping by independent review mutation-positive by NGS Secondary endpoints Tepotin
Slide 4: Methods
Methods • Single-arm, open-label, Phase II trial conducted at ~90 sites in Belgium, France, Germany, Italy, Japan, Poland, Spain, and the USA • Patients will receive tepotinib monotherapy 500 mg QD on 21-day cycles until disease progression, intolerable toxicity, or withdrawal of consent • Objective
Slide 5: Baseline Patient and Tumor Characteristics
Baseline Patient and Tumor Characteristics Characteristic Tepotinib 500 mg (N=38)* Median age, years (range) 73.0 (39–89) Gender, n (%) Male 25 (65.8) Race,† n (%) White 27 (71.1) Asian 9 (23.7) Smoking history,‡ n (%) Never smoker 12 ( 31.6) Former smoker 17 ( 44.7) Regular smoker 1 ( 2.6) Brain me
Slide 6: Efficacy: Best Overall Response Independent Review
Efficacy: Best Overall Response Independent Review • Efficacy analysis includes only patients having at least 2 post-baseline assessments or who discontinued treatment for any reason (n=28) L+ T+ Combined analysis Tepotinib 500 mg (n=16) (n=26) set (n=28) Best overall response by RECIST 1.1 Complete
Slide 7: Efficacy: Best Overall Response Investigator Assessment
Efficacy: Best Overall Response Investigator Assessment • Efficacy analysis includes only patients having at least 2 post-baseline assessments or who discontinued treatment for any reason (n=28) L+ T+ Combined analysis Tepotinib 500 mg (n=16) (n=26) set (n=28) Best overall response by RECIST 1.1 Com
Slide 8: Efficacy: Change in Sum of Target Lesion Diameter, Independent Review
Efficacy: Change in Sum of Target Lesion Diameter Independent Review 100 T+ L+ 80 T+ only 60 L+ only of target lesion diameters Percent change in sum 40 Neither T+ nor L+ (information missing) PD NE* 20 PD PD 0 PD PD NE SD -20 NE NE* SD NE* SD SD SD SD NE* -40 PR PD PR PR PR NE* PR -60 PR PR PR PR P
Slide 9: Efficacy: Change in Sum of Target Lesion Diameter, Investigator Assessment
Efficacy: Change in Sum of Target Lesion Diameter Investigator Assessment 100 T+ L+ 80 T+ only 60 L+ only of target lesion diameters Percent change in sum 40 Neither T+ nor L+ (information missing) PD 20 NE* PD NE PD 0 NE SD -20 SD PD SD SD NE* -40 PR PR NE* SD NE* PR PR PR PR PR NE* -60 PR NE* PR P
Slide 10: Time on Treatment and Duration of Response
Time on Treatment and Duration of Response Independent Review 2 PR 2 PR 2 PR 0 SD Prior lines of anticancer therapy (n) 1 PR 0 SD 1 0 0 SD PR SD • Median duration of response 1 PR 1 2 0 PD SD PR (95% confidence interval)§: 3 1 1 PD PR PR 12.39 (2.79, 15.74) months 0 SD 0 PR L+ only 0 PD 2 PR T+ only
Slide 11: Safety Results
Safety Results Tepotinib 500 mg (N=38) Tepotinib 500 mg (N=38) All TEAEs* Serious TEAEs Any grade Grade ≥3 Any grade Grade ≥3 ≥1 TEAE 34 (89.5) 18 (47.4) Serious TEAEs, n (%) 15 (39.5) 13 (34.2) ≥1 drug-related TEAE, n (%) 26 (68.4) 7 (18.4) ≥1 serious drug-related TREAE, n (%) 4 (10.5) 3 (7.9) Drug
Slide 12: Conclusions
Conclusions • Tepotinib shows encouraging signs of activity in patients with advanced NSCLC harboring METexon14-skipping mutations • The best OR to date based on independent review is partial response in 12/28 (42.9%) evaluable patients • Median duration of response (95% confidence interval) is 12.3
Slide 13: Acknowledgements
Acknowledgements • We thank the patients and their families • We thank the investigators, co-investigators, and the study teams at each participating center and at Merck KGaA, Darmstadt, Germany • The trial was sponsored by Merck KGaA, Darmstadt, Germany • Editorial assistance was provided by Bioscr