Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme

Conditions

Glioblastoma Multiforme

Keywords

GBM

Brief summary

This study is evaluating the safety and pharmacokinetics of ABT-414 in subjects with glioblastoma multiforme.

Hui Gan, Aidan Seow, Eddie Lau, Sze-Ting Lee, Malaka Ameratunga et al. (12 authors)

Neuro-Oncology2018-11-012 citations

10.1093/neuonc/noy148.087

Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with<i>EGFR</i>-amplified, recurrent glioblastoma: results from an international phase I multicenter trial

Andrew B. Lassman, Martin J. van den Bent, Hui Gan, David A. Reardon, Priya Kumthekar et al. (24 authors)

Neuro-Oncology2018-06-1194 citations

10.1093/neuonc/noy091

ACTR-68. CONCORDANCE OF EGFR AND MGMT ANALYSES BETWEEN LOCAL AND CENTRAL LABORATORIES: IMPLICATIONS FOR CLINICAL TRIAL DESIGN AND PRECISION MEDICINE FOR DEPATUXIZUMAB-MAFODOTIN (ABT-414) IN GLIOBLASTOMA (GBM)

Andrew B. Lassman, Cara Dimino, Mahesh Mansukhani, Vundavalli V. Murty, Peter Ansell et al. (12 authors)

Neuro-Oncology2017-11-018 citations

10.1093/neuonc/nox168.055

PDCT-02. EVALUATION OF DEPATUXIZUMAB MAFODOTIN (ABT-414) IN CHILDREN WITH HIGH GRADE GLIOMA (HGG) AND DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Martin J. van den Bent, Birgit Geoerger, Vassilis Golfinopoulos, Peter Ansell, Earle Bain et al. (10 authors)

Neuro-Oncology2017-11-011 citations

10.1093/neuonc/nox168.746

Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study.

van den Bent M, Gan HK, Lassman AB, Kumthekar P, Merrell R, Butowski N, Lwin Z, Mikkelsen T, Nabors LB, Papadopoulos KP, Penas-Prado M, Simes J, Wheeler H, Walbert T, Scott AM, Gomez E, Lee HJ, Roberts-Rapp L, Xiong H, Bain E, Ansell PJ, Holen KD, Maag D, Reardon DA.

2017-10-2699 citations

10.1007/s00280-017-3451-1

Efficacy analysis of ABT-414 with or without temozolomide (TMZ) in patients (pts) with EGFR-amplified, recurrent glioblastoma (rGBM) from a multicenter, international phase I clinical trial.

Andrew B. Lassman, Martin J. van den Bent, Hui Gan, David A. Reardon, Priya Kumthekar et al. (20 authors)

Journal of Clinical Oncology2017-05-209 citations

10.1200/jco.2017.35.15_suppl.2003

OS07.4 Efficacy of a novel antibody-drug conjugate (ADC), ABT-414, as monotherapy in epidermal growth factor receptor (EGFR) amplified (EGFRamp), recurrent glioblastoma (rGBM)

Martin J. van den Bent, Hui Gan, Andrew B. Lassman, P. Kumthekar, Nicholas Butowski et al. (9 authors)

Neuro-Oncology2017-04-015 citations

10.1093/neuonc/nox036.045

P09.25 Identifying the correct patient (pt) population for ABT414: biomarker assays for epidermal growth factor receptor (EGFR) in pts with glioblastoma (GBM)

Andrew B. Lassman, Hui Gan, L. Robert-Rapp, Peter Ansell, Ryan Merrell et al. (10 authors)

Neuro-Oncology2017-04-012 citations

10.1093/neuonc/nox036.281

ACTR-07. EFFICACY OF A NOVEL ANTIBODY-DRUG CONJUGATE (ADC), ABT-414, AS MONOTHERAPY IN EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) AMPLIFIED (EGFRamp), RECURRENT GLIOBLASTOMA (rGBM)

Martin J. van den Bent, Hui Gan, Andrew B. Lassman, Priya Kumthekar, Ryan Merrell et al. (22 authors)

Neuro-Oncology2016-11-012 citations

10.1093/neuonc/now212.006

Efficacy of a novel antibody-drug conjugate (ADC), ABT-414, as monotherapy in epidermal growth factor receptor (EGFR) amplified, recurrent glioblastoma (GBM).

Martin J. van den Bent, Hui Gan, Andrew B. Lassman, Priya Kumthekar, Ryan Merrell et al. (20 authors)

Journal of Clinical Oncology2016-05-209 citations

10.1200/jco.2016.34.15_suppl.2542

ATNT-01ABT-414 MONO- OR COMBINATION THERAPY WITH TEMOZOLOMIDE (TMZ) RECHALLENGE IN PATIENTS WITH RECURRENT GLIOBLASTOMA (GBM) AND AMPLIFIED EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR): A PHASE I STUDY

Hui Gan, Priya Kumthekar, Andrew B. Lassman, Ryan Merrell, Martin J. van den Bent et al. (18 authors)

Neuro-Oncology2015-11-014 citations

10.1093/neuonc/nov205.01

Phase I study of ABT-414 mono- or combination therapy with temozolomide (TMZ) in recurrent glioblastoma (GBM).

Hui Gan, Kyriakos P. Papadopoulos, Lisa Fichtel, Andrew B. Lassman, Ryan Merrell et al. (20 authors)

Journal of Clinical Oncology2015-05-2020 citations

10.1200/jco.2015.33.15_suppl.2016

A phase 1 study evaluating ABT-414 in combination with temozolomide (TMZ) for subjects with recurrent or unresectable glioblastoma (GBM).

Hui Gan, Lisa Fichtel, Andrew B. Lassman, Ryan Merrell, Martin J. van den Bent et al. (18 authors)

Journal of Clinical Oncology2014-05-2022 citations

10.1200/jco.2014.32.15_suppl.2021

Interventions

DRUGABT-414

ABT-414 will be administered by intravenous infusion

DRUGTemozolomide

Temozolomide will be administered per label and local prescribing regulations.

RADIATIONWhole Brain Radiation

Whole Brain radiation will be administered in 30 fractions.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

Healthy volunteers

No

Inclusion criteria

1. Glioblastoma Multiforme (GBM) 2. 70 or above on Karnofsky Performance Status 3. Adequate bone marrow function 4. Recurrent GBM per RANO criteria 5. Subjects must have confirmed EGFR amplification by central lab

Exclusion criteria

1. For Subjects with recurrent GBM in Arm B, subject has received prior treatment with bevacizumab, nitrosourea, or has secondary GBM 2. For Subjects with recurrent GBM in Arm C, subject has received prior treatment with bevacizumab, or has secondary GBM 3. Allergies to temozolomide, dacarbazine, IgG containing agents 4. Anti-cancer treatment 28 days prior to study Day 1, except in Arm B expanded cohort temozolomide therapy is allowed 5. Subjects that have had more than one disease recurrence

Design outcomes

Primary

Measure	Time frame	Description
Half-life of ABT-414	Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks	Measurement of the clearance of ABT-414
Maximum concentration of ABT-414	Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks	Measurement of the maximum concentration of ABT- 414 in the blood
Number of Dose Limiting Toxicities	Every week for an expected average of 34 weeks	Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG)
Minimum Concentration of ABT-414	Multiple time points in Cycles 1, 2, and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment, an expected average of 34 weeks	Measurement of the minimum concentration of ABT-414 in the blood
Number and percentage of participants with adverse events	Every week for an expected average of 34 weeks	Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG)

Secondary

Measure	Time frame	Description
Progression Free Survival	Multiple time points in each cycle, throughout study, and survival information monthly until 1 year after last visit, or the participant becomes lost to follow up, or study termination.	Progression Free Survival per RANO criteria is the length of time during and after the treatment of a disease, that the participant lives with the disease but does not get worse.
Overall Survival	Multiple time points in each cycle, throughout study, and survival information monthly until 1 year after last visit, or participant becomes lost to follow up, or study termination	The overall response rate will be evaluated every 8 weeks at each assessment of disease according to RANO criteria, up to 28 months
Biomarker EGFR expression	At screening and post-study	Assessment of tumor biomarkers that may correlate with efficacy.

Outcome results

None listed