September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Corneal Toxicity of ABT-414 in Glioblastoma (GBM): Clinical Manifestations, Ophthalmological Findings and Management
Author Affiliations & Notes
  • Marian Macsai
    NorthShore University Health System, Evanston, Illinois, United States
  • Ashiyana Nariani
    Duke University Eye Center, Durham, North Carolina, United States
  • Hui Gan
    Austin Health and Olivia Newton-John Cancer Research Institute, Melbourne, Victoria, Australia
  • Andrew Lassman
    Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, United States
  • Ryan Merrell
    NorthShore University Health System, Evanston, Illinois, United States
  • Erica Gomez
    AbbVie Inc., North Chicago, Illinois, United States
  • Rajendar Mittapalli
    AbbVie Inc., North Chicago, Illinois, United States
  • Hao Xiong
    AbbVie Inc., North Chicago, Illinois, United States
  • Christopher Ocampo
    AbbVie Inc., North Chicago, Illinois, United States
  • Kyle Holen
    AbbVie Inc., North Chicago, Illinois, United States
  • Golnaz Moazami
    Harkness Eye Institute Columbia Medical Center, New York, New York, United States
  • Footnotes
    Commercial Relationships   Marian Macsai, None; Ashiyana Nariani, None; Hui Gan, AbbVie, Inc. (F), AbbVie, Inc. (R), Ludwig Institute for Cancer Research (S), Merck Serono (R), Pfizer (R); Andrew Lassman, AbbVie (F), AbbVie, Inc. (R), Agenus (F), Amgen (F), Angiochem (F), Boehringer Ingelheim (F), Celldex (F), Foundation Medicine (R), Genentech (R), Genentech (F), Heron (R), Karyopharm (F), Medimmune (F), Novartis (R), Novartis (F), Novocure, Stemline, E-Therapeutics, Millennium (F), NW Biotherapeutics (F), Pfizer (F), Plexxicon (F), Regeneron (R); Ryan Merrell, None; Erica Gomez, AbbVie, Inc. (I), AbbVie, Inc. (E); Rajendar Mittapalli, AbbVie, Inc. (I), AbbVie, Inc. (E); Hao Xiong, AbbVie, Inc. (I), AbbVie, Inc. (E); Christopher Ocampo, AbbVie, Inc. (I), AbbVie, Inc. (E); Kyle Holen, AbbVie, Inc. (I), AbbVie, Inc. (E); Golnaz Moazami, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 269. doi:
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      Marian Macsai, Ashiyana Nariani, Hui Gan, Andrew Lassman, Ryan Merrell, Erica Gomez, Rajendar Mittapalli, Hao Xiong, Christopher Ocampo, Kyle Holen, Golnaz Moazami; Corneal Toxicity of ABT-414 in Glioblastoma (GBM): Clinical Manifestations, Ophthalmological Findings and Management. Invest. Ophthalmol. Vis. Sci. 2016;57(12):269.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : ABT-414 is an antibody-drug conjugate consisting of a toxin, MMAF (monomethyl auristatin F), linked to an anti-EGFR antibody (ABT-806). Although there is promising antitumor activity of ABT-414 in GBM, it has been associated with corneal toxicity (CT). The pathophysiology of these toxicities is poorly understood. Herein we report the manifestations and management of CTs associated with ABT-414 in GBM.

Methods : M12-356 (NCT01800695) is an open-label, phase 1, 3-arm study: Arm A (ABT-414+radiation (RT)/ temozolomide (TMZ) in newly diagnosed GBM (nGBM)), Arm B (ABT-414+TMZ either in nGBM as adjuvant therapy, or in recurrent GBM (rGBM)) and Arm C (ABT-414 monotherapy in rGBM). Severity of each ocular adverse event (AE) was rated according to NCI CTCAE Version 4.1. The dose-toxicity relationship was analyzed by logistic regression and the onset of CTs was determined by Kaplan-Meier analysis.

Results : As of September 29, 2015, total number of patients reported with one or more ocular treatment-emergent AEs (TEAEs) were 40/45 (89%, Arm A), 42/48 (88%, Arm B) and 59/74 (80%, Arm C). Most common TEAEs (≥25% in at least one arm) for Arms A/B/C respectively, were blurred vision (64%/52%/53%), dry eye (36%/17%/24%), keratitis (33%/25%/20%) and photophobia (33%/38%/24%). Most common Grade (G) 3/4 TEAEs (≥10% in at least one arm) were keratitis (13%/15%/14%) and blurred vision (11%/6%/4%). Overall percent ocular G3/4 TEAEs were 27%/25%/28%. An apparent dose-toxicity relationship was observed in each arm. Median onset times of G2 or higher CTs were comparable among all arms at recommended phase 2 doses, ranging from 49-65 days. Manifestations included microcystic keratopathy, corneal crystals, stromal opacities, limbal stem cell deficiency, punctate epithelial erosion, and filament/corneal abrasions. Management included prophylactic dexamethasone or prednisolone acetate (PA) eye drops, and treatment with bandage contact lenses, punctal plugs, topical preservative-free artificial tears, antibiotics, PA, and/or cyclosporine eye drops. For G3/4 toxicities, ABT-414 was held until toxicity resolved and re-treatment began at a lower dose.

Conclusions : Frequent CTs were observed with ABT-414 treatment in GBM. However, the promising antitumor activity of ABT-414 in GBM warrants further evaluation into strategies to help manage or prevent these toxicities.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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