First-in-Human Phase I, Dose-Escalation and -Expansion Study of Telisotuzumab Vedotin, an Antibody-Drug Conjugate Targeting c-Met, in Patients With Advanced Solid Tumors.

Autor:	Strickler JH; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Weekes CD; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Nemunaitis J; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Ramanathan RK; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Heist RS; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Morgensztern D; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Angevin E; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Bauer TM; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Yue H; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Motwani M; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Parikh A; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Reilly EB; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Afar D; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Naumovski L; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL., Kelly K; John H. Strickler, Duke University Medical Center, Durham, NC; Colin D. Weekes, University of Colorado, Aurora, CO; John Nemunaitis, Mary Crowley Cancer Research Center, Dallas, TX; Ramesh K. Ramanathan, Virginia Piper Cancer Center at Honor Health/Translational Genomics Research Institute, Scottsdale, AZ; Rebecca S. Heist, Massachusetts General Hospital Cancer Center, Boston, MA; Daniel Morgensztern, Washington University School of Medicine, St. Louis, MO; Eric Angevin, Gustave Roussy, Villejuif, France; Todd M. Bauer, Sarah Cannon Research Institute; Todd M. Bauer, Tennessee Oncology, Nashville, TN; Huibin Yue, Daniel Afar, and Louie Naumovski, AbbVie Inc.; Apurvasena Parikh, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Redwood City; Karen Kelly, University of California Davis Comprehensive Cancer Center, Sacramento, CA; and Monica Motwani, Edward B. Reilly, AbbVie Inc., North Chicago, IL.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2018 Nov 20; Vol. 36 (33), pp. 3298-3306. Date of Electronic Publication: 2018 Oct 04.
DOI:	10.1200/JCO.2018.78.7697
Abstrakt:	Purpose: This first-in-human study evaluated telisotuzumab vedotin (Teliso-V), formerly called ABBV-399, an antibody-drug conjugate of the anti-c-Met monoclonal antibody ABT-700 and monomethyl auristatin E. Materials and Methods: For dose escalation, three to six patients with advanced solid tumors were enrolled in eight cohorts (0.15 to 3.3 mg/kg). The dose-expansion phase enrolled patients with non-small-cell lung cancer (NSCLC) with c-Met-overexpressing tumors (c-Met positive; immunohistochemistry membrane H-score ≥ 150). Patients received Teliso-V monotherapy intravenously on day 1 once every 3 weeks. Safety, tolerability, pharmacokinetics, and maximum tolerated dose were determined. Results: Forty-eight patients were enrolled (median age, 65 years; 35.4% NSCLC; median four prior therapies). One patient each in the 3.0-mg/kg (n = 9) and 3.3-mg/kg (n = 3) cohorts experienced dose-limiting toxicities. Although the maximum tolerated dose was not formally identified, the recommended phase II dose was defined as 2.7 mg/kg on the basis of overall safety and tolerability. The most frequent treatment-emergent adverse events (any grade) were fatigue (42%), nausea (27%), constipation (27%), decreased appetite (23%), vomiting (21%), dyspnea (21%), diarrhea (19%), peripheral edema (19%), and neuropathy (17%). The most frequent Teliso-V-related grade ≥ 3 adverse events were fatigue, anemia, neutropenia, and hypoalbuminemia (4% each). Teliso-V and total antibody pharmacokinetics were approximately dose proportional, with a mean harmonic half-life of 2 to 4 days each. Prospective screening identified 35 (60%) of 58 patients with c-Met-positive NSCLC. Of 16 patients with c-Met-positive NSCLC who were treated with Teliso-V 2.4 to 3.0 mg/kg, three (18.8%; 95% CI, 4.1% to 45.7%) achieved a partial response (median response duration, 4.8 months; median progression-free survival, 5.7 months; 95% CI, 1.2 months to 15.4 months). No other patients experienced a response. Conclusion: Teliso-V monotherapy demonstrated favorable safety and tolerability profiles, with encouraging evidence of antitumor activity in patients with c-Met-positive NSCLC.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu