Clinical trial NCT02343406: Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas
Official title: INTELLANCE-2: ABT-414 Alone or ABT-414 Plus Temozolomide Versus Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase 2 Study of the EORTC Brain Tumor Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Keywords: Glioblastoma
Epithelial Growth Factor vIII mutation
Temozolomide
Lomustine
ABT-414
European Organization for Research and Treatment of Cancer
Recurrent glioblastoma
Epithelial Growth Factor
Brain Tumor
Brain Tumor Group
Antibody Drug Conjugate
EORTC
Pediatric High Grade Gliomas
Pediatric Diffuse Intrinsic Pontine Glioma
Pediatric WHO grade III glioma
Pediatric WHO grade IV glioma
EGFR amplification
Children
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
First posted: 2015-01-22
Enrollment: 266
Sex: ALL
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.

Detailed description: The study objectives were to assess whether depatuxizumab mafodotin (ABT-414) alone or in combination with temozolomide (TMZ) improved overall survival (OS), progression-free survival (PFS), tumor response, quality of life, neurological deterioration-free survival (NDFS), and steroid use compared to standard treatment with lomustine single agent or TMZ re-challenge in adult subjects ≥ 18 years of age with centrally-confirmed recurrent epidermal growth factor receptor (EGFR)-amplified glioblastoma. The safety, pharmacokinetics, and efficacy of depatuxizumab mafodotin in children \<18 years of age was evaluated in a pediatric substudy. The EMEA-001732-PIP02-15 pediatric investigation plan was withdrawn on 07 July 2019 due to the discontinuation of the depatuxizumab mafodotin research program.

Eligibility criteria: Inclusion Criteria:

Adult participants (greater than or equal to 18 years old):

* Histologically confirmed de novo (primary) glioblastoma with unequivocal tumor progression or recurrence.
* In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy
* Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial.
* Availability of adequate biological material (formalin-fixed paraffin embedded \[FFPE\] tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification
* Presence of EGFR amplification confirmed by central assessment; participants with undetermined EGFR status are excluded
* World Health Organization (WHO) Performance status 0 - 2
* No more than one line of chemotherapy (concurrent and adjuvant Temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
* Post surgery MRI within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization.
* Surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators.
* Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula.
* Liver function: bilirubin \< 1.5× upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) \< 2.5× ULN

Pediatric sub-study participants (less than 18 years old):

* Histologically proven high grade glioma (HGG: WHO grade III glioma \[e.g anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma\], grade IV glioma \[e.g. glioblastoma, gliosarcoma\] or diffuse intrinsic pontine glioma \[DIPG\]).
* Must either have recurrent/progressive tumor or, if newly diagnosed, have completed any planned radiation therapy at least 4 weeks prior to first dose of ABT-414.
* The tumor tissue must have been determined to have EGFR amplification, (by local or other testing service).
* Availability of adequate biological material for retrospective confirmatory central testing of EGFR amplification
* Participant has sufficiently recovered from previous therapy. The investigator believes that benefit of treating the pediatric subject with ABT-414 outweighs the expected risks and that this treatment is in the best interests of the pediatric subject.
* Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula for pediatric patients ≥12 years of age and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m\^2 by modified Schwartz equation for pediatric patients \< 12 years of age.
* Liver function: Total bilirubin ≤ 1.5× upper limit of the normal range (ULN), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) \<= 3× ULN. Participants with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is \< 3 times ULN. Not allowed are participants with known chronic liver disease and/or cirrhosis.

Exclusion Criteria:

Adult population (greater than or equal to 18 years old):

* Prior treatment with nitrosoureas
* Prior treatment with bevacizumab
* Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents, including EGFRvIII targeting agents
* Prior discontinuation of temozolomide chemotherapy for toxicity reasons
* Prior Radiation Therapy (RT) with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
* Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
* No history of wheat allergies and Coeliac disease.
* No EIAED, patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to randomization.

Pediatric sub-study (less than 18 years old):

* (For recurrent disease) No prior RT with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
* No current or recent (within 4 weeks or 5 half-lives \[whichever is shorter\] before enrollment) treatment with another investigational drug
* Female participants of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.

Primary outcomes:
measure: Adult Study: Overall Survival (OS)
timeFrame: From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months.
measure: Adult Study: Progression-Free Survival (PFS)
timeFrame: Measured every 8 weeks from date of randomization until the date of first objective progression or subject's death, whichever occurred first, up to 2 years
measure: Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug
timeFrame: From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks
measure: Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414
timeFrame: Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
measure: Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF
timeFrame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8
measure: Pediatric Study: Half-life (t1/2) Observed for ABT-414
timeFrame: Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
measure: Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF
timeFrame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8
measure: Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414
timeFrame: Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose
measure: Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF
timeFrame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Secondary outcomes:
measure: Adult Study: Objective Response Rate (ORR)
timeFrame: Every 8 weeks at each assessment of disease, up to 28 months
measure: Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation
timeFrame: From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months
measure: Pediatric Study: Objective Response Rate (ORR)
timeFrame: Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
measure: Pediatric Study: Best Tumor Response Rate
timeFrame: Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
measure: Pediatric Study: Duration of Response
timeFrame: Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks
measure: Pediatric Study: Overall Survival
timeFrame: From the date of enrollment to the date of death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months
measure: Pediatric Study: Time to Progression
timeFrame: Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks
measure: Pediatric Study: Progression-Free Survival
timeFrame: Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks
measure: Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning
timeFrame: Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hosp /ID# 153678
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado /ID# 153677
state: Colorado
city: Aurora
country: United States
facility: Univ of Colorado Cancer Center /ID# 134882
state: Colorado
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE - Denver /ID# 141798
state: Colorado
city: Chicago
country: United States
facility: Rush University Medical Center /ID# 137542
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 154210
state: Massachusetts
city: Lake Success
country: United States
facility: Long Island Brain Tumor Center /ID# 134496
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine /ID# 152656
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus /ID# 137540
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh MC /ID# 134491
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC /ID# 134492
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center /ID# 136718
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center /ID# 136719
state: Washington
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital /ID# 134569
state: New South Wales
city: Randwick
country: Australia
facility: Sydney Children's Hospital /ID# 153533
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital /ID# 147092
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle /ID# 134570
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Ctr /ID# 134495
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital /ID# 147091
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital /ID# 135208
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital /ID# 135209
state: Tasmania
city: Geelong
country: Australia
facility: Barwon Health University Hospital Geelong /ID# 134493
state: Victoria
city: Melbourne
country: Australia
facility: Royal Children's Hospital /ID# 157624
state: Victoria
city: St. Pölten
country: Austria
facility: University Hospital St. Polten /ID# 139070
state: Niederoesterreich
city: Graz
country: Austria
facility: LKH-Univ. Klinikum Graz /ID# 139071
city: Linz
country: Austria
facility: Kepler Universitätsklinikum GmbH - Neuromed Campus /ID# 139068
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint Luc /ID# 139391
state: Bruxelles-Capitale
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi /ID# 139342
state: Hainaut
city: Gent
country: Belgium
facility: UZ Gent /ID# 152944
state: Oost-Vlaanderen
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge-Oostende AV /ID# 137927
state: West-Vlaanderen
city: Antwerp
country: Belgium
facility: ZNA Middelheim /ID# 137926
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 137925
city: Montreal
country: Canada
facility: Montreal Neurological Institut /ID# 136309
state: Quebec
city: Prague 5
country: Czechia
facility: Fakultni Nemocnice v Motole /ID# 139509
state: Praha 5
city: Brno
country: Czechia
facility: Masarykuv onkologikcy ustav /ID# 139508
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove /ID# 139510
city: Ostrava
country: Czechia
facility: Univ Hosp Ostrava-Poruba /ID# 139507
city: Helsinki
country: Finland
facility: Helsinki Univ Central Hospital /ID# 140078
city: Helsinki
country: Finland
facility: Helsinki Univ Central Hospital /ID# 153069
city: Turku
country: Finland
facility: Turku University Hospital /ID# 140861
city: Lille CEDEX
country: France
facility: CHRU Lille - Hôpital Claude Huriez /ID# 137916
state: Hauts-de-France
city: Lille
country: France
facility: Centre Oscar Lambret /ID# 169619
state: Hauts-de-France
city: Bobigny
country: France
facility: CHU-Hopital Avicenne /ID# 137910
state: Ile-de-France
city: Villejuif
country: France
facility: Gustave Roussy /ID# 137912
state: Ile-de-France
city: St Herblain CEDEX
country: France
facility: Institut de Cancer de l'Ouest /ID# 137914
state: Loire-Atlantique
city: Marseille CEDEX 05
country: France
facility: Hopital de la Timone /ID# 137911
state: Provence-Alpes-Cote-d Azur
city: Nice CEDEX 1
country: France
facility: CHU de Nice /ID# 137917
state: Provence-Alpes-Cote-d Azur
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 137918
state: Rhone
city: Angers
country: France
facility: Institut de Cancer de l'Ouest /ID# 137909
city: Bron
country: France
facility: Hospices Civils de Lyon /ID# 137913
city: Paris
country: France
facility: Hopital Pitie Salpetriere /ID# 145887
city: Heidelberg
country: Germany
facility: Universitaetsklinik Heidelberg /ID# 137924
state: Baden-Wuerttemberg
city: Ratisbon
country: Germany
facility: Universitatsklinik Regensburg /ID# 137920
state: Bayern
city: Hamburg
country: Germany
facility: Univ Klinik Eppendorf Hamburg /ID# 137921
city: Munich
country: Germany
facility: LMU Klinikum der Universität München /ID# 137922
city: Tuebingen
country: Germany
facility: Universitatsklinikum Tubingen /ID# 137923
city: Pécs
country: Hungary
facility: Pecsi Tudomanyegyetem /ID# 136111
state: Pecs
city: Budapest
country: Hungary
facility: Semmelweis Egyetem /ID# 152578
city: Budapest
country: Hungary
facility: National Institute of Oncology /ID# 135970
city: Budapest
country: Hungary
facility: Orszagos Klinikai Idegtudomany /ID# 135971
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ /ID# 135969
city: Cork
country: Ireland
facility: Cork University Hospital /ID# 136828
city: Dublin
country: Ireland
facility: Beaumont Hospital /ID# 136829
city: Bologna
country: Italy
facility: Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 138335
city: Bolzano
country: Italy
facility: Ospedale Generale di Bolzano /ID# 138338
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 140395
city: Padova
country: Italy
facility: Istituto Oncologico Veneto /ID# 138336
city: Rome
country: Italy
facility: Azienda Ospedaliera Sant' Andrea /ID# 138337
city: Seongnam
country: Korea, Republic of
facility: Seoul National Univ Bundang ho /ID# 136841
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 136842
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 136840
city: San Pedro Garza García
country: Mexico
facility: Hospital Zambrano Hellion /ID# 138076
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum /ID# 137221
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen /ID# 138266
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum /ID# 136981
city: The Hague
country: Netherlands
facility: Haaglanden Medisch Centrum /ID# 137222
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 137219
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum /ID# 204409
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne /ID# 137919
state: Mazowieckie
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistycz /ID# 137654
city: Singapore
country: Singapore
facility: National University Hospital /ID# 135951
city: Singapore
country: Singapore
facility: National Cancer Ctr Singapore /ID# 135952
city: Singapore
country: Singapore
facility: KK Women's & Children Hospital /ID# 153676
city: Badalona
country: Spain
facility: Instituto Catalán de Oncología (ICO) Badalona /ID# 140976
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universitar de Navarra - Pamplona /ID# 140047
state: Navarra, Comunidad
city: Barcelona
country: Spain
facility: Instituto Catalan de Oncologia (ICO) & Hosp. de Bellvitge /ID# 137688
city: Madrid
country: Spain
facility: Hospital Universitario Nino /ID# 153800
city: Madrid
country: Spain
facility: Hosp Univ 12 de Octubre /ID# 137908
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Univ Vaudoi /ID# 137929
city: Zurich
country: Switzerland
facility: University Hospital Zurich /ID# 137930
city: Taichung City
country: Taiwan
facility: China Medical University Hosp /ID# 136976
state: Taichung
city: Taipei City
country: Taiwan
facility: National Taiwan Univ Hosp /ID# 136975
state: Taipei
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hosp /ID# 136977
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 136974
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Ho /ID# 136944
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Found /ID# 140312
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Univ Hospitals Birmingham NHS Foundation trust /ID# 136978
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital /ID# 136979
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire NHS /ID# 136917
city: London
country: United Kingdom
facility: University College Hospitals /ID# 136879
city: London
country: United Kingdom
facility: Great Ormond St Hospital NHS /ID# 153421
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust /ID# 140313
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Clement PMJ, Dirven L, Eoli M, Sepulveda-Sanchez JM, Walenkamp AME, Frenel JS, Franceschi E, Weller M, Chinot O, De Vos FYFL, Whenham N, Sanghera P, Looman J, Kundu MG, Peter de Geus J, Nuyens S, Spruyt M, Gorlia T, Coens C, Golfinopoulos V, Reijneveld JC, van den Bent MJ. Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma. Eur J Cancer. 2021 Apr;147:1-12. doi: 10.1016/j.ejca.2021.01.010. Epub 2021 Feb 15.
citation: Van Den Bent M, Eoli M, Sepulveda JM, Smits M, Walenkamp A, Frenel JS, Franceschi E, Clement PM, Chinot O, De Vos F, Whenham N, Sanghera P, Weller M, Dubbink HJ, French P, Looman J, Dey J, Krause S, Ansell P, Nuyens S, Spruyt M, Brilhante J, Coens C, Gorlia T, Golfinopoulos V. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma. Neuro Oncol. 2020 May 15;22(5):684-693. doi: 10.1093/neuonc/noz222.
citation: Lassman AB, van den Bent MJ, Gan HK, Reardon DA, Kumthekar P, 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, Ansell PJ, Bain E, Holen KD, Maag D, Merrell R. Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial. Neuro Oncol. 2019 Jan 1;21(1):106-114. doi: 10.1093/neuonc/noy091.
citation: Gan 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.
citation: Reardon 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.