PMID- 37257422 OWN - NLM STAT- MEDLINE DCOM- 20240110 LR - 20240110 IS - 1423-0259 (Electronic) IS - 0030-3747 (Print) IS - 0030-3747 (Linking) VI - 66 IP - 1 DP - 2023 TI - A Phase 3b Study for Management of Ocular Side Effects in Patients with Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin. PG - 1030-1043 LID - 10.1159/000531142 [doi] AB - INTRODUCTION: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries. METHODS: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status >/=70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were to be randomized (1:1:1) to OSE prophylactic treatments with each depatuxizumab mafodotin infusion: (a) standard steroid eye drops, (b) standard steroid eye drops plus vasoconstrictor eye drops and cold compress, or (c) enhanced steroids plus vasoconstrictor eye drops and cold compress. A Corneal Epitheliopathy Adverse Event (CEAE) scale was devised to capture symptoms, grade OSEs (scale of 0-5), and inform ADC dose modifications. The primary endpoint was the frequency of a required change in OSE management due to inadequate control of OSEs, defined as decline from baseline in visual acuity (using logarithm of the minimum angle of resolution [LogMAR] scale) or a Grade >/=3 CEAE event, in the worst eye in the first 8 weeks of treatment; unless otherwise specified, the treatment period refers to both the chemoradiation and adjuvant phases. RESULTS: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin. Forty patients were randomized (38 received depatuxizumab mafodotin). Overall, 23 patients experienced inadequate control of OSEs that required change in OSE management within 8 weeks of treatment, with 21 (70.0%) experiencing >/=+0.3 change on LogMAR scale in baseline-adjusted visual acuity and 12 reporting a grade >/=3 CEAE. There were no definitive differences among prophylactic treatments. CONCLUSIONS: The premature cessation of the study precludes definitive conclusions regarding the OSE prophylaxis strategies. No new clinically significant safety findings were noted. Despite these limitations, this study highlights the need for novel assessment tools to better understand and mitigate OSEs associated with ADCs. CI - (c) 2023 The Author(s). Published by S. Karger AG, Basel. FAU - Vize, Colin J AU - Vize CJ AD - Department of Ophthalmology, Hull University Teaching Hospitals NHS Trust, Hull, UK. FAU - Kim, Stella K AU - Kim SK AD - Department of Ophthalmology and Visual Science, University of Texas McGovern Medical School, Houston, Texas, USA. FAU - Matthews, Tim AU - Matthews T AD - Birmingham Neuro-Ophthalmology Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. FAU - Macsai, Marian AU - Macsai M AD - Northshore University Health System, Glenview, Illinois, USA. FAU - Merrell, Ryan AU - Merrell R AD - NorthShore University Health System, Evanston, Illinois, USA. FAU - Hsu, Sigmund AU - Hsu S AD - The Vivian L. Smith Department of Neurosurgery, University of Texas McGovern Medical School, Houston, Texas, USA. FAU - Kundu, Madan Gopal AU - Kundu MG AD - AbbVie, North Chicago, Illinois, USA. FAU - Yoon, Jennifer AU - Yoon J AD - AbbVie, North Chicago, Illinois, USA. FAU - Kennedy, Emma AU - Kennedy E AD - AbbVie, North Chicago, Illinois, USA. FAU - Pai, Madhavi AU - Pai M AD - AbbVie, North Chicago, Illinois, USA. FAU - Bain, Earle AU - Bain E AD - AbbVie, North Chicago, Illinois, USA. FAU - Lassman, Andrew B AU - Lassman AB AD - Division of Neuro-Oncology, Department of Neurology and the Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian, New York, New York, USA. FAU - Moazami, Golnaz AU - Moazami G AD - Department of Ophthalmology, Columbia University Irving Medical Center, New York, NY, USA. LA - eng GR - P30 CA013696/CA/NCI NIH HHS/United States GR - UG1 CA189960/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20230531 PL - Switzerland TA - Ophthalmic Res JT - Ophthalmic research JID - 0267442 RN - F3R7A4P04N (depatuxizumab mafodotin) RN - EC 2.7.10.1 (ErbB Receptors) RN - 0 (Ophthalmic Solutions) RN - 0 (Steroids) RN - YF1K15M17Y (Temozolomide) RN - 0 (Vasoconstrictor Agents) SB - IM MH - Adult MH - Humans MH - ErbB Receptors/metabolism MH - *Glioblastoma/drug therapy/metabolism/pathology MH - Ophthalmic Solutions/therapeutic use MH - Steroids/therapeutic use MH - Temozolomide/therapeutic use MH - Vasoconstrictor Agents/therapeutic use PMC - PMC10413800 OTO - NOTNLM OT - Antibody-drug conjugate OT - Corneal epitheliopathy OT - Depatuxizumab mafodotin OT - Epidermal growth factor receptor OT - Ocular side effect COIS- Colin J. Vize is a member of AbbVie advisory board. Stella K. Kim is ophthalmology consultant for AbbVie, Astellas, Cytomx, ImmunoGen, SeattleGenetics, Zymeworks. Tim Matthews is a member of AbbVie advisory board and receives Novartis educational stipend. Madan G. Kundu, Jennifer Yoon, Emma Kennedy, Madhavi Pai, and Earle Bain are AbbVie employees and may hold stock or options. Andrew B. Lassman reports grants, personal fees, and nonfinancial support from AbbVie; personal fees and nonfinancial support from Abbott Molecular, during the conduct of the study; personal fees and nonfinancial support from Bioclinica as an expert blinded independent reviewer of clinical and imaging data for a BMS-sponsored trial, grants, personal fees, and nonfinancial support from Karyopharm; personal fees from Sapience; personal fees and nonfinancial support from Novocure, grants, personal fees, and nonfinancial support from QED; personal fees and nonfinancial support from Forma, grants, personal fees, and nonfinancial support from Bayer, grants, personal fees, and nonfinancial support from Orbus, personal fees and nonfinancial support from NW Biotherapeutics, grants, personal fees, and nonfinancial support from Agios; personal fees from WebMD; personal fees, and nonfinancial support from Celgene; personal fees from prIME Oncology, grants and nonfinancial support from Kadmon, grants and nonfinancial support from VBI, grants and nonfinancial support from Beigene, grants and nonfinancial support from Oncoceutics, nonfinancial support from Tocagen, grants and nonfinancial support from Pfizer, grants and nonfinancial support from Genentech/Roche, grants and nonfinancial support from Millenium, grants and nonfinancial support from Celldex, grants and nonfinancial support from Novartis, nonfinancial support from Aeterna Zentaris, personal fees and nonfinancial support from PER, grants and nonfinancial support from BMS, outside the submitted work. Marian Macsai, Ryan Merrell, Sigmund Hsu, and Golnaz Moazami have nothing to disclose. EDAT- 2023/06/01 01:08 MHDA- 2023/12/25 06:43 PMCR- 2023/05/31 CRDT- 2023/05/31 18:22 PHST- 2021/10/14 00:00 [received] PHST- 2023/05/09 00:00 [accepted] PHST- 2023/12/25 06:43 [medline] PHST- 2023/06/01 01:08 [pubmed] PHST- 2023/05/31 18:22 [entrez] PHST- 2023/05/31 00:00 [pmc-release] AID - 000531142 [pii] AID - 531142 [pii] AID - 10.1159/000531142 [doi] PST - ppublish SO - Ophthalmic Res. 2023;66(1):1030-1043. doi: 10.1159/000531142. Epub 2023 May 31.