4823 - An open-label, multicenter, phase 1 study of ABBV-399 (telisotuzumab vedotin, teliso-V) as monotherapy (T) and in combination with erlotinib (T+E) in non-small cell lung cancer (NSCLC)

Background

Teliso-V is a c-Met–targeted antibody and MMAE drug conjugate, with a t_1/2 of ∼2–4 days. We updated data analyses of T schedule of administration (q2w vs q3w) and T+E in c-Met+ NSCLC pts.

Methods

T doses ranged from 2.4–3.0 mg/kg (dose expansion [DE] at 2.7 mg/kg) q3w or at doses from 1.6–2.2 mg/kg (DE at 1.9 mg/kg) q2w to pts with advanced c-Met + (IHC H-score ≥150) NSCLC and q3w at 2.7 mg/kg in combo with E 150 mg qd (NCT02099058). c-Met IHC staining was centrally assessed with the SP44 Ab (Ventana; Tucson, AZ). EGFR activating mutation (EGFR M+) status was defined per local report. PK sampling was performed.

Results

As of Feb 9, 2018, 50 pts received ≥1 dose of T; 8 of 23 (35%) pts on T+E were EGFR M+ and c-MET+. Rate of c-MET+ among screened NSCLC pts with adenocarcinoma and squamous (Sq) histologies was 64% and 42%, respectively. Monotherapy (q2w vs q3w) all grades (Gr; ≥40%) adverse events (AEs): fatigue (50% vs 59%), neuropathy (NP; 57% vs 23%), and nausea (36% vs 41%); Gr ≥ 3 (≥10%): anemia (7% vs 18%). All Gr T+E (≥20%): NP (39%), hypoalbuminemia (26%), dermatitis acneiform (26%)/rash (13%), pulmonary embolism (PE), diarrhea, and nausea (22%, each); Gr ≥ 3 (≥10%) AE: PE (22%). Median time to NP onset was 3.3 months (95% CI: 1.5–5.6) among 17 T-related NPs. Higher T trough concentrations that were observed with q2w than with q3w correlated with Gr ≥ 2 NP (p = 0.014) and indicated a trend of higher ORR (p = 0.202). See table for efficacy: T exposure data by histologies, T dosing, and EGFR M+ pts on T+E.

Conclusions

Safety profiles between T treatment schedules were comparable except for more NP for q2w schedule; potentially due to longer treatment duration. In the non-Sq subgroup a trend of better efficacy was observed with q2w than q3w; 1.9 mg/kg q2w was selected as the RP2D for T moving forward. Promising activity was seen for T+E in EGFR M+ and c-MET+ NSCLC and warrants continued evaluation.

Clinical trial identification

NCT02099058.

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc.

Editorial Acknowledgement

Medical writing support was provided by Mary L. Smith, PhD, CMPP, from TRM Oncology, Atlanta, GA, and funded by AbbVie.

Disclosure

J. Goldman: Research funding: AbbVie. E. Angevin: Consultant: Merck Sharp & Dohme, GlaxoSmithKline; Research funding: AbbVie, Roche, Sanofi; Travel, accommodations, expenses: AbbVie, Roche, and Sanofi. J. Strickler: Consultant: Amgen, Bayer, Boehringer Ingelheim, Celgene, Genentech; Research funding: AbbVie, Bayer, Exelixis, Gilead Sciences, MedImmune, OncoMed, Regeneron, Sanofi. D. Morgensztern: Consultant: Bristol-Myers Squibb, Celgene. T.M. Bauer: Consultant: Ignyta, Guardant Health, Loxo, Pfizer, Moderna Therapeutics; Research funding: Daiichi Sankyo, Medpacto, Inc., Incyte, Mirati Therapeutics, MedImmune, AbbVie, AstraZeneca, Leap Therapeutics, MabVax, Stemline Therapeutics, Merck, Lilly, GlaxoSmithKline, Novartis, Pfizer, Principia Biopharma, Genentech/Roche, Deciphera, Merrimack, Immunogen, Millennium, Ignyta, Calithera Biosciences, Kolltan Pharmaceuticals, Principia Biopharma, Peloton, Immunocore, Roche, Aileron Therapeutics, Bristol-Myers Squibb, Amgen, Moderna Therapeutics, Sanofi, Boehringer Ingelheim, Astellas Pharma, Five Prime Therapeutics, Jacobio. E.E. Vokes: Consultant: AbbVie, Amgen, Ariad, AstraZeneca, Bayer, Biolumina, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, EMD Serono, Genentech, Leidos, Novartis, Merck, Regeneron, Takeda, VentiRx. T. Yi, M. Motwani, A. Parikh, J. Wu: Employed and may own stock: AbbVie. K. Kelly: Consultant: AbbVie, AstraZeneca, Genentech, Janssen, Lilly, Merck; Travel, accommodation, expenses: AbbVie, AstraZeneca, Genentech, Janssen, Lilly, Merck; Honoraria: Merck; Research funding: AbbVie, Celgene, EMD Serono, Five Prime, Genentech, Lilly, Lycera, Novartis, Regeneron, Transgene. All other authors have declared no conflicts of interest.Table: 1383PD

RECIST version 1.1. EGFR M+, epidermal growth factor receptor activating mutation; EGFR WT, epidermal growth factor receptor wildtype; NR, not reached; NSCLC, non-small cell lung cancer; nSq, non-squamous; PFS, progression-free survival; q2w, once every 14 days; q3w, once every 21 days; Sq, squamous; RECIST, Response Evaluation Criteria In Solid Tumors; T, teliso-V monotherapy; T+E, teliso-V plus erlotinib.