138O - Efficacy of a novel antibody-drug conjugate (ADC), ABT-414, with temozolomide (TMZ) in recurrent glioblastoma (rGBM)

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session CNS tumours
Topics Anti-Cancer Agents & Biologic Therapy
Central Nervous System Malignancies
Presenter Martin van den Bent
Citation Annals of Oncology (2016) 27 (suppl_9): ix42-ix45. 10.1093/annonc/mdw578
Authors M. van den Bent1, A.B. Lassman2, H.K. Gan3, D.A. Reardon4, P. Kumthekar5, N. Butowski6, Z. Lwin7, T. Mikkelsen8, L.B. Nabors9, K.P. Papadopoulos10, M. Penas-Prado11, J. Simes12, H. Wheeler13, E. Gomez14, H. Lee14, L. Roberts-Rapp14, H. Xiong14, E. Bain14, K. Holen14, R. Merrell15
  • 1Neuro-oncology, Erasmus MC Cancer Institute, 3075 EA - Rotterdam/NL
  • 2Department Of Neurology & Herbert Irving Comprehensive Cancer Center, Columbia University, 60064 - New York/US
  • 3Medical Oncology, Austin Health and Olivia Newton-John Cancer Research Institute; Department of Medicine, University of Melbourne; La Trobe University School of Cancer Medicine, Melbourne/AU
  • 4Neuro-oncology, Dana-Farber Cancer Institute, Boston/US
  • 5Department Of Neurology, Northwestern University, Chicago/US
  • 6Department Of Neurological Surgery, University of California, San Francisco/US
  • 7Department Of Medical Oncology, University of Queensland School of Medicine, Royal Brisbane and Women's Hospital, Brisbane/AU
  • 8Neurosurgery And Neuroscience Research, Henry Ford Health System, Detroit/US
  • 9Department Of Neurobiology, University of Alabama at Birmingham, Birmingham/US
  • 10Department Of Clinical Research, South Texas Accelerated Research Therapeutics (START), Houston/US
  • 11Department Of Neuro-oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 12Nhmrc Clinical Trials Centre, University of Sydney, Sydney/AU
  • 13Medical Oncology, Royal North Shore Hospital, Sydney/AU
  • 14Global Pharmaceutical R&d, AbbVie Inc., North Chicago/US
  • 15Department Of Neurology, NorthShore University Health System, Evanston/US

Abstract

Background

ABT-414 is a first-in-class ADC that selectively targets EGFR amplification (amp) to deliver a potent microtubule cytotoxin (monomethyl auristatin F) inside the tumor cells. Almost 50% of GBMs harbor EGFR amp. ABT414 monotherapy has shown preliminary efficacy in EGFR amp rGBM. Here we report safety and efficacy of ABT-414+TMZ in EGFR amp rGBM at the recommended phase 2 dose.

Methods

Adults with rGBM harboring centrally-confirmed EGFR amp, adequate endorgan function, and KPS >70 were eligible. To isolate the effects of ABT-414 from TMZ, all patients (pt)s were TMZ refractory, defined as a recurrent/progressive disease

Results

As of March 1, 2016, 32 pts were treated following 1 (n = 21), 2 (n = 8), or > 3 (n = 1) prior therapies. The most common adverse events (AE)s (≥25% pts) were blurred vision (53%), photophobia (34%), headache (34%), fatigue (31%) and constipation (25%). Grade 3/4 AEs included (>1 pt) keratitis (16%), ataxia, decreased platelet count, hemiparesis and thrombocytopenia (6% each). Seizure was the most common serious AE, occurring in 13% pts. Neurologic AEs were generally attributed to the underlying tumor. No doselimiting toxicities were observed. Best radiographic responses in 31 pts with available imaging data were: 3 (10%) partial responses (PR), 18 (58%) stable disease (SD), and 10 (32%) progressive disease (PD). Pts with PD were allowed a repeat resection as clinically indicated. Four of them were found to have all or mainly treatment effect rather than active recurrence on histologic analysis; the progressionfree survival (PFS), response, and 6 month-PFS rates will be updated after clarifying their outcomes.

Conclusions

In this TMZ refractory population, ABT-414 demonstrated 10% PR and 58% SD rates, although histology of tissue resected for presumed recurrence remains to be clarified, which may increase rate of disease control. No new safety events were observed and ocular toxicity was the most common AE. A global, randomized trial of ABT-414 alone or with TMZ, vs. TMZ or lomustine, is underway in rGBM (NCT02343406).

Clinical trial indentification

NCT01800695

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc.

Disclosure

M. van den Bent: Received honoraria from Roche, Abbvie, Celldex, Novocure, Merck Ag, Cavion, Actelion, BMS, Blue Earth Diagnostics; received research funding from AbbVie and Roche. A.B. Lassman: Received personal compensation within the last 12 months from VBI Vaccines, Sapience Therapeutics, Cortice Biosciences, prIME Oncology, Abbvie, Genentech, Regeneron; Research support from Genentech, Amgen, AbbVie, Novartis, Karyopharm, Celldex, NW Biotherapeutics, Plexxicon, Pfizer, Agenus, Medimmune, Boehringer Ingelheim, Angiochem, Novocure, Stemline, E-Therapeutics, Millennium. H.K. Gan: Has an investigator-initiated study with AbbVie; received travel support and research funding from AbbVie; received honoraria from AbbVie, Pfizer and Merck Serono; affiliated with the Ludwig Institute for Cancer Research. D.A. Reardon: Received honoraria from and has a consulting or advisory role with Abbvie, Bristol Myers Squibb, Cavion, Celldex, Inovio, Merck, Novartis, Roche/Genentech, Amgen, Novocure, Oxigene, Regeneron and Stemline Therapeutics; is involved in speakers’ bureaus with Roche and Merck; received research funding from Incyte, Midatech and Celldex. P. Kumthekar: Received Honoraria for advisory role with AbbVie within the last 12 months. N. Butowski: Received honoraria from and has a consulting or advisory role with, Roche/Genentech, Medicenna, VBL Therapeutics, Omniox, Celldex; is involved in speakers’ bureaus with Roche and Merck; received research funding Insys. L.B. Nabors: Serves on a Scientific Advisory Board for Cavion. K.P. Papadopoulos: Received research funding from AbbVie, MedImmune, Daiichi Sankyo, GlaxoSmithKline, Onyx, Sanofi, Novartis. E. Gomez, H-J. Lee, L. Roberts-Rapp, H. Xiong, E. Bain, K. Holen: Employed by AbbVie and may own AbbVie stock. R. Merrell: Received honoraria for advisory role with Abbvie. All other authors have declared no conflicts of interest.