A phase 1b study of the MET inhibitor capmatinib combined with cetuximab in patients with MET-positive colorectal cancer
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PHASE I STUDIES
A phase 1b study of the MET inhibitor capmatinib combined with cetuximab in patients with MET-positive colorectal cancer who had progressed following anti-EGFR monoclonal antibody treatment Jean-Pierre Delord 1 & Guillem Argilés 2 & Jerôme Fayette 3 & Lori Wirth 4 & Stefan Kasper 5 & Salvatore Siena 6 & Ricard Mesia 7 & Rossana Berardi 8 & Andrés Cervantes 9 & Jeroen Dekervel 10 & Sylvia Zhao 11 & Yongjian Sun 11 & Huai-Xiang Hao 12 & Ralph Tiedt 13 & Sergio Vicente 13 & Andrea Myers 11 & Lillian L. Siu 14 Received: 7 February 2020 / Accepted: 19 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary Background Overcoming resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in patients with KRAS wildtype (WT) metastatic colorectal cancer (mCRC) could help meet the needs of patients with limited treatment options. Methods In this phase 1b study, patients with N/KRAS WT, MET-positive mCRC who had progressed following antiEGFR mAb treatment received escalating oral doses of capmatinib (150, 300, and 400 mg) twice daily plus weekly intravenous cetuximab (at the approved dose). The primary objective was to establish a recommended dose for expansion (RDE) of capmatinib in combination with cetuximab. Safety, preliminary activity, pharmacokinetics, and pharmacodynamics were also explored. Results Thirteen patients were enrolled. No patients experienced a dose-limiting toxicity at investigated doses; the RDE was established as capmatinib 400 mg twice daily plus cetuximab. All patients experienced adverse events (AEs) suspected to be related to the study treatment. Five patients (38.5%) reported study-drug–related AEs of grade 3/4 in severity. No patients achieved a complete or partial response according to RECIST v1.1; however, tumor shrinkage of 29–44% was observed in 4 patients. Conclusions Capmatinib plus cetuximab was well tolerated. Preliminary signs of activity were observed. Further investigation is warranted to obtain efficacy data and refine predictive biomarkers of response. Clinical trial registration NCT02205398. Keywords Capmatinib . Cetuximab . MET positive . Colorectal cancer . Phase I Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10637-020-00928-z) contains supplementary material, which is available to authorized users. 7
Medical Oncology Department, Catalan Institut of Oncology – Hospitalet, IDIBELL, Barcelona, Spain
8
Medical Oncology, Università Politecnica delle Marche-Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Ancona, Italy
9
CIBERONC, Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain
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Department of Oncology, University Hospital Leuven, Leuven, Belgium
11
Novartis Institutes for BioMedical Research, Shanghai, China
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany
12
Novartis Institutes for BioMedical Research, Cambridge, MA, US
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