TY - JOUR
T1 - A Phase 1b Study of Telisotuzumab Vedotin in Combination With Nivolumab in Patients With NSCLC
AU - Camidge, D. Ross
AU - Barlesi, Fabrice
AU - Goldman, Jonathan W.
AU - Morgensztern, Daniel
AU - Heist, Rebecca
AU - Vokes, Everett
AU - Angevin, Eric
AU - Hong, David S.
AU - Rybkin, Igor I.
AU - Barve, Minal
AU - Bauer, Todd M.
AU - Delmonte, Angelo
AU - Dunbar, Martin
AU - Motwani, Monica
AU - Parikh, Apurvasena
AU - Noon, Elysa
AU - Wu, Jun
AU - Blot, Vincent
AU - Kelly, Karen
N1 - Funding Information:
Disclosure: Dr. Camidge reports serving as an advisor for AbbVie, Apollomics, AstraZeneca, Daiichi Sankyo, Elevation, Kestrel, Nuvalent, Seattle Genetics, Takeda, Turning Point, Amgen, Anchiano, Bio-Thera, Bristol-Myers Squibb, Eisai, EMD Serono, Eli Lilly, GlaxoSmithKline, Helsinn, Janssen, OnKure, Mersana, Pfizer, Qilu, Roche, Sanofi, CBT Pharmaceuticals, G1 Therapeutics, Blueprint, Achilles, BeyondSpring, Archer, Medtronic, and Ribon; receiving research funding from Inivata; and participating at company-sponsored trials (institution) by AbbVie, AstraZeneca, Dizal, Inhibrx, Karyopharm, Pfizer, Phosplatin, PsiOxus, Rain, Roche/Genentech, Seattle Genetics, Takeda, and Turning Point. Dr. Barlesi reports having a consulting or advisory role with Roche/Genentech, Pfizer, Novartis, Pierre Fabre, Bristol-Myers Squibb, AstraZeneca/MedImmune, Boehringer Ingelheim, Eli Lilly, Merck Serono, Merck Sharp & Dohme Oncology, and Takeda; received funding for travel, accommodations, and expenses from Roche/Genentech, Bristol-Myers Squibb, and AstraZeneca/MedImmune; honoraria from Roche/Genentech, Pfizer, Novartis, Pierre Fabre, Bristol-Myers Squibb, AstraZeneca/MedImmune, Boehringer Ingelheim, Lilly, Merck Serono, Merck Sharp & Dohme Oncology, and Takeda; and research funding from Roche/Genentech, AstraZeneca/MedImmune, Bristol-Myers Squibb, and Pierre Fabre. Dr. Angevin reports having a consulting or advisory role and conducting research for Merck Sharp & Dohme, GlaxoSmithKline, Celgene, and MedImmune; and received funding for travel, accommodations, and expenses from AbbVie, Roche, Sanofi, Pfizer, and MedImmune. Dr. Bauer reports serving as a consultant for Guardant Health, Ignyta, Loxo, and Pfizer; and received research funding from AbbVie, Aileron Therapeutics, Amgen, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Daiichi Sankyo, Deciphera, Genentech/Roche, GlaxoSmithKline, Ignyta, Immunocore, ImmunoGen, Incyte, Kolltan Pharmaceuticals, Leap Therapeutics, Eli Lilly, MabVax, MedImmune, MedPacto Inc., Merck, Merrimack, Millennium, Mirati Therapeutics, Moderna Therapeutics, Novartis, Peloton, Pfizer, Principia Biopharma, Roche, Sanofi, and Stemline Therapeutics. Dr. Delmonte reports serving as a consultant or participant in advisory boards for Bristol-Myers Squibb, AstraZeneca, Roche, and Takeda, and as principal investigator of some clinical trials by AbbVie. Drs. Dunbar, Motwani, Parikh, Noon, Wu, and Blot are employees of AbbVie and may own stock. Dr. Goldman reports receiving research funding from AbbVie and Genentech/Roche; consulting fees from Genentech; and research funding and consulting fees from AbbVie, Bristol-Myers Squibb, and Genentech. Dr. Heist reports receiving honoraria as a consultant from Boehringer Ingelheim, Tarveda, and Novartis; serving as consultant from Apollomics, Daichii Sankyo, and EMD Serono; and received research funding for institution (not to self) from Agios, AbbVie, Daichii Sankyo, Exelixis, Novartis, Turning Point, Eli Lilly, and Mirati. Dr. Hong reports receiving research/grant funding from AbbVie, Adaptimmune, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa, Eli Lilly, Loxo, Merck, MedImmune, Mirati, MiRNA Therapeutics, Molecular Templates, Mologen, NCI CTEP, Novartis, Pfizer, Seattle Genetics, and Takeda; funding for travel, accommodations, and expenses from Loxo, MiRNA Therapeutics, American Society of Clinical Oncology, American Association for Cancer Reasearch, Society for Immunotherapy of Cancer, and Genmab; has consulting or advisory role at AlphaSights, Axiom, Adaptimmune, Baxter, Bayer, Genentech, GLG, groupH, Guidepoint Global, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, and Trieza Therapeutics; and other ownership interests from MolecularMatch (advisor), OncoResponse (founder), and Presagia Inc. (advisor). Dr. Kelly reports serving as a consultant for Eli Lilly, AbbVie, AstraZeneca, Genentech, Janssen, and Merck; received funding for travel, accommodations, and expenses from AbbVie, AstraZeneca, Genentech, Janssen, Eli Lilly, and Merck; author royalties from UpToDate; honoraria from Merck; and research funding from AbbVie, Celgene, EMD Serono, Five Prime, Genentech, Novartis, Regeneron, and TransGene. Dr. Morgensztern reports serving as a consultant for AbbVie, Gilead, Bristol-Myers Squibb, Takeda, PharmaMar, Lilly, and G1 Therapeutics. Dr. Rybkin reports participating at company-sponsored trials (institution) by AbbVie, AstraZeneca/MedImmune, Bayer, Jiangsu Alphamab Biopharmaceutical, Bergenbio, Iovance Biotherapeutics, Rain, Sanofi, Eli Lilly, Roche, Genentech, Seattle Genetics, Mirati, Merck Sharp & Dohme, Novartis, Nitto BioPharma, Bristol-Myers Squibb, and Merck Serono. Dr. Vokes reports receiving honoraria/consultancy fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, Genentech, Novartis, Merck, and Regeneron. The remaining authors declare no conflict of interest.
Funding Information:
AbbVie, Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. ABBV-399 uses ABT-700, an antibody licensed from Pierre Fabre, and ADC technology licensed from Seattle Genetics. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie and the authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Mary L. Smith, PhD, CMPP, Aptitude Health, Atlanta, GA, funded by AbbVie.
Publisher Copyright:
© 2021 The Authors
PY - 2022/1
Y1 - 2022/1
N2 - Introduction: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met–directed antibody-drug conjugate that has exhibited antitumor activity as monotherapy in NSCLC. Its potential activity combined with programmed cell death protein-1 inhibitors has not been previously evaluated. Methods: In a phase 1b study (NCT02099058), adult patients (≥18 y) with advanced NSCLC received combination therapy with Teliso-V (1.6, 1.9, or 2.2 mg/kg, every 2 wk) plus nivolumab (3 mg/kg, 240 mg, or per locally approved label). The primary objective was to assess safety and tolerability; secondary objectives included the evaluation of antitumor activity. Results: As of January 2020, a total of 37 patients received treatment with Teliso-V (safety population) in combination with nivolumab; 27 patients (efficacy population) were c-Met immunohistochemistry–positive. Programmed death-ligand 1 (PD-L1) status was evaluated in the efficacy population (PD-L1–positive [PD-L1+]: n = 15; PD-L1–negative [PD-L1–]: n = 9; PD-L1–unknown: n = 3). The median age was 67 years and 74% (20 of 27) of patients were naive to immune checkpoint inhibitors. The most common any-grade treatment-related adverse events were fatigue (27%) and peripheral sensory neuropathy (19%). The pharmacokinetic profile of Teliso-V plus nivolumab was similar to Teliso-V monotherapy. The objective response rate was 7.4%, with two patients (PD-L1+, c-Met immunohistochemistry H-score 190, n = 1; PD-L1–, c-Met H-score 290, n = 1) having a confirmed partial response. Overall median progression-free survival was 7.2 months (PD-L1+: 7.2 mo; PD-L1–: 4.5 mo; PD-L1–unknown: not reached). Conclusions: Combination therapy with Teliso-V plus nivolumab was well tolerated in patients with c-Met+ NSCLC with limited antitumor activity.
AB - Introduction: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met–directed antibody-drug conjugate that has exhibited antitumor activity as monotherapy in NSCLC. Its potential activity combined with programmed cell death protein-1 inhibitors has not been previously evaluated. Methods: In a phase 1b study (NCT02099058), adult patients (≥18 y) with advanced NSCLC received combination therapy with Teliso-V (1.6, 1.9, or 2.2 mg/kg, every 2 wk) plus nivolumab (3 mg/kg, 240 mg, or per locally approved label). The primary objective was to assess safety and tolerability; secondary objectives included the evaluation of antitumor activity. Results: As of January 2020, a total of 37 patients received treatment with Teliso-V (safety population) in combination with nivolumab; 27 patients (efficacy population) were c-Met immunohistochemistry–positive. Programmed death-ligand 1 (PD-L1) status was evaluated in the efficacy population (PD-L1–positive [PD-L1+]: n = 15; PD-L1–negative [PD-L1–]: n = 9; PD-L1–unknown: n = 3). The median age was 67 years and 74% (20 of 27) of patients were naive to immune checkpoint inhibitors. The most common any-grade treatment-related adverse events were fatigue (27%) and peripheral sensory neuropathy (19%). The pharmacokinetic profile of Teliso-V plus nivolumab was similar to Teliso-V monotherapy. The objective response rate was 7.4%, with two patients (PD-L1+, c-Met immunohistochemistry H-score 190, n = 1; PD-L1–, c-Met H-score 290, n = 1) having a confirmed partial response. Overall median progression-free survival was 7.2 months (PD-L1+: 7.2 mo; PD-L1–: 4.5 mo; PD-L1–unknown: not reached). Conclusions: Combination therapy with Teliso-V plus nivolumab was well tolerated in patients with c-Met+ NSCLC with limited antitumor activity.
KW - Antibody-drug conjugate
KW - Nivolumab
KW - Non–small cell lung cancer
KW - Telisotuzumab vedotin
KW - c-Met
UR - http://www.scopus.com/inward/record.url?scp=85121820843&partnerID=8YFLogxK
U2 - 10.1016/j.jtocrr.2021.100262
DO - 10.1016/j.jtocrr.2021.100262
M3 - Article
C2 - 35005654
AN - SCOPUS:85121820843
SN - 2666-3643
VL - 3
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
IS - 1
M1 - 100262
ER -