A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification

This study seeks to determine whether the addition of ABT-414 to concomitant radiotherapy and temozolomide (TMZ) followed by combination of ABT-414 with adjuvant TMZ prolongs overall survival (OS) among participants with newly diagnosed glioblastoma (GBM) with epidermal growth factor receptor (EGFR) amplification. In addition, there is a Phase 1, open-label, multicenter sub-study to assess the pharmacokinetics, safety and tolerability of ABT-414 in participants with newly diagnosed EGFR-amplified GBM who have mild or moderate hepatic impairment.

Sex

All

Minimum age

18 Years

Maximum age

99 Years

Inclusion Criteria:

* Must have a clinical diagnosis of glioblastoma (GBM).
* Must have a confirmed epidermal growth factor receptor amplification in tumor tissue.
* Must have a Karnofsky Performance Status (KPS) \>= 70 at assessment \<= 14 days prior to randomization (N/A to the sub-study).
* Must have recovered from effects of surgery, postoperative infection and other complications of surgery.
* Must have adequate bone marrow, renal, and hepatic function (For the sub-study, the participant must have adequate bone marrow and renal function and have mild-to-moderate hepatic impairment).

Exclusion Criteria:

* Multifocal, recurrent or metastatic GBM or gliomatosis cerebri (For the sub-study, the participant can have multifocal GBM and glimatosis cerebri but can't have recurrent or metastatic GBM).
* Prior chemo therapy or radiosensitizer for head and neck cancer.
* Prior radiotherapy to the head or neck in overlap of radiation fields.
* Prior therapy for glioblastoma or other invasive malignancy.
* Prior, concomitant or planned treatment with Novo Tumor Treatment Fields (Novo-TTF), EGFR-targeted therapy, bevacizumab, Gliadel wafers or other intratumoral or intracavity anti-neoplastic therapy.

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• DERIVEDGan HK, Reardon DA, Lassman AB, Merrell R, van den Bent M, Butowski N, Lwin Z, Wheeler H, Fichtel L, Scott AM, Gomez EJ, Fischer J, Mandich H, Xiong H, Lee HJ, Munasinghe WP, Roberts-Rapp LA, Ansell PJ, Holen KD, Kumthekar P. Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma. Neuro Oncol. 2018 May 18;20(6):838-847. doi: 10.1093/neuonc/nox202. PMID 29077941
• DERIVEDReardon DA, Lassman AB, van den Bent M, Kumthekar P, Merrell R, Scott AM, Fichtel L, Sulman EP, Gomez E, Fischer J, Lee HJ, Munasinghe W, Xiong H, Mandich H, Roberts-Rapp L, Ansell P, Holen KD, Gan HK. Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neuro Oncol. 2017 Jul 1;19(7):965-975. doi: 10.1093/neuonc/now257. PMID 28039367