TY - JOUR
T1 - Phase I dose-escalation and -expansion study of telisotuzumab (ABT-700), an Anti-c-met antibody, in patients with advanced solid tumors
AU - Strickler, John H.
AU - LoRusso, Patricia
AU - Salgia, Ravi
AU - Kang, Yoon Koo
AU - Yen, Chia Jui
AU - Lin, Chia Chi
AU - Ansell, Peter
AU - Motwani, Monica
AU - Wong, Shekman
AU - Yue, Huibin
AU - Wang, Lan
AU - Reilly, Edward
AU - Afar, Daniel
AU - Naumovski, Louie
AU - Ramanathan, Ramesh K.
N1 - Funding Information:
J.H. Strickler is a consultant at Seattle Genetics, Roche/Genentech, Amgen, reports receiving a commercial research grant from Seattle Genetics, Exelixis, AbbVie, Roche/Genentech, and Amgen. P.M. LoRusso is a consultant/advisory board member at AbbVie, Agios, Cybrexa, Agenus, Tyme, IQVIA, TRIGR, Pfizer, I-MAB, ImmunoMet, Black Diamond, GlaxoSmithKline, Five Prime, QED Therapeutics, AstraZeneca, EMD Serono, Shattuck, Astellas, Salarius, Silverback, MacroGenics, GenMab, Halozyme, Roche-Genentech, Genentech, CytomX, Takeda, and SOTIO. Y.-K. Kang is a consultant at Ono, BMS, ALX Oncology, Zymeworks, Amgen, Novartis, and Daehwa. C.-C. Lin is a consultant at Novartis, Boehringer-Ingelheim, Daiichi-Sankyo, has received speakers' bureau honoraria from Novartis, Roche. P. Ansell is a senior principal research scientist at AbbVie. M. Motwani is a research fellow at AbbVie. S. Wong is a director of clinical
Funding Information:
AbbVie and the authors thank the patients who participated in this clinical trial, the study coordinators, and support staff. This study was funded by AbbVie Inc., North Chicago, IL, USA. Medical writing support was provided by Mary L. Smith, PhD, CMPP, Aptitude Health, Atlanta, GA, funded by AbbVie. AbbVie Inc. provided financial support for the study and participated in the design, study conduct, analysis and interpretation of data, as well as the writing, review, and approval of the manuscript. Telisotuzumab (ABT-700) is an antibody licensed from Pierre Fabre to AbbVie.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5-25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days. For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed. The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.
AB - This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5-25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days. For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed. The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.
UR - http://www.scopus.com/inward/record.url?scp=85084272832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084272832&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-19-0529
DO - 10.1158/1535-7163.MCT-19-0529
M3 - Article
C2 - 32127466
AN - SCOPUS:85084272832
VL - 19
SP - 1210
EP - 1217
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
SN - 1535-7163
IS - 5
ER -