TY - JOUR
T1 - Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer
AU - Camidge, D. Ross
AU - Barlesi, Fabrice
AU - Goldman, Jonathan W.
AU - Morgensztern, Daniel
AU - Heist, Rebecca
AU - Vokes, Everett
AU - Spira, Alex
AU - Angevin, Eric
AU - Su, Wu Chou
AU - Hong, David S.
AU - Strickler, John H.
AU - Motwani, Monica
AU - Dunbar, Martin
AU - Parikh, Apurvasena
AU - Noon, Elysa
AU - Blot, Vincent
AU - Wu, Jun
AU - Kelly, Karen
N1 - Funding Information:
AbbVie and the authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Rebecca L. Crepeau, PhD, from Aptitude Health, Atlanta, GA, and funded by AbbVie.
Funding Information:
Supported by AbbVie, Inc, which funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the publication. ABBV-399 uses ABT-700, an antibody licensed from Pierre Fabre, and antibody-drug conjugate 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
Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/2/10
Y1 - 2023/2/10
N2 - PURPOSEOverexpression of c-Met protein and epidermal growth factor receptor (EGFR) mutations can co-occur in non-small-cell lung cancer (NSCLC), providing strong rationale for dual targeting. Telisotuzumab vedotin (Teliso-V), a first-in-class antibody-drug conjugate targeting c-Met, has shown a tolerable safety profile and antitumor activity as monotherapy. Herein, we report the results of a phase Ib study (ClinicalTrials.gov identifier: NCT02099058) evaluating Teliso-V plus erlotinib, an EGFR tyrosine kinase inhibitor (TKI), in patients with c-Met-positive (+) NSCLC.PATIENTS AND METHODSThis study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age ≥ 18 years) with c-Met+ NSCLC. Later enrollment required presence of an EGFR-activating mutation (EGFR-M+) and progression on a prior EGFR TKI. End points included safety, pharmacokinetics, objective response rate (ORR), and progression-free survival (PFS). The efficacy-evaluable population consisted of c-Met+ patients (confirmed histology [H]-score ≥ 150) who had at least one postbaseline scan; c-Met+ patients with H-scores ≥ 225 were classified as c-Met high.RESULTSAs of January 2020, 42 patients were enrolled (N = 36 efficacy-evaluable). Neuropathies were the most common any-grade adverse events reported, with 24 of 42 patients (57%) experiencing at least one event. The pharmacokinetic profile of Teliso-V plus erlotinib was similar to Teliso-V monotherapy. Median PFS for all efficacy-evaluable patients was 5.9 months (95% CI, 2.8 to not reached). ORR for EGFR-M+ patients (n = 28) was 32.1%. Of EGFR-M+ patients, those who were c-Met high (n = 15) had an ORR of 52.6%. Median PFS was 6.8 months for non-T790M+ and for those whose T790M status was unknown, versus 3.7 months for T790M+.CONCLUSIONTeliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR TKI-pretreated patients with EGFR-M+, c-Met+ NSCLC.
AB - PURPOSEOverexpression of c-Met protein and epidermal growth factor receptor (EGFR) mutations can co-occur in non-small-cell lung cancer (NSCLC), providing strong rationale for dual targeting. Telisotuzumab vedotin (Teliso-V), a first-in-class antibody-drug conjugate targeting c-Met, has shown a tolerable safety profile and antitumor activity as monotherapy. Herein, we report the results of a phase Ib study (ClinicalTrials.gov identifier: NCT02099058) evaluating Teliso-V plus erlotinib, an EGFR tyrosine kinase inhibitor (TKI), in patients with c-Met-positive (+) NSCLC.PATIENTS AND METHODSThis study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age ≥ 18 years) with c-Met+ NSCLC. Later enrollment required presence of an EGFR-activating mutation (EGFR-M+) and progression on a prior EGFR TKI. End points included safety, pharmacokinetics, objective response rate (ORR), and progression-free survival (PFS). The efficacy-evaluable population consisted of c-Met+ patients (confirmed histology [H]-score ≥ 150) who had at least one postbaseline scan; c-Met+ patients with H-scores ≥ 225 were classified as c-Met high.RESULTSAs of January 2020, 42 patients were enrolled (N = 36 efficacy-evaluable). Neuropathies were the most common any-grade adverse events reported, with 24 of 42 patients (57%) experiencing at least one event. The pharmacokinetic profile of Teliso-V plus erlotinib was similar to Teliso-V monotherapy. Median PFS for all efficacy-evaluable patients was 5.9 months (95% CI, 2.8 to not reached). ORR for EGFR-M+ patients (n = 28) was 32.1%. Of EGFR-M+ patients, those who were c-Met high (n = 15) had an ORR of 52.6%. Median PFS was 6.8 months for non-T790M+ and for those whose T790M status was unknown, versus 3.7 months for T790M+.CONCLUSIONTeliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR TKI-pretreated patients with EGFR-M+, c-Met+ NSCLC.
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U2 - 10.1200/JCO.22.00739
DO - 10.1200/JCO.22.00739
M3 - Article
C2 - 36288547
AN - SCOPUS:85147720764
SN - 0732-183X
VL - 41
SP - 1105
EP - 1115
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 5
ER -