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

Glioblastoma Clinical Trial

— INTELLANCE-2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02343406
• Other study ID #: M14-483
• Secondary ID: 2014-004438-24EO
• Status: Completed
• Phase: Phase 2
• Start date: February 17, 2015
• Est. completion date: June 24, 2019

Study information

• Verified date: May 2020
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 The EMEA-001732-PIP02-15 pediatric investigation plan was withdrawn on 07 July 2019 due to the discontinuation of the depatuxizumab mafodotin research program.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: June 24, 2019
• Est. primary completion date: June 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Depatuxizumab mafodotin
Adults: intravenous administration (1.25 mg/kg or 1.0 mg/kg body weight) over 30 to 40 minutes once every 2 weeks until one of the treatment withdrawal criteria was met. The dose was 1.25 mg/kg in the original protocol (Version 1) and Version 2, Amendment 1, and was lowered to 1.0 mg/kg in protocol Version 3, Amendment 2. Pediatric participants: Intravenous administration (1.0 mg/kg body weight for those who were 6 to 17 years old at the date of first dose, or 1.3 mg/kg for those who were 0 to 5 years old) over 30 to 40 minutes or as directed by the guidelines once every 2 weeks until one of the treatment withdrawal criteria was met, for a maximum of one year. If used in combination with temozolomide, depatuxizumab mafodotin was dosed on Day 1 and Day 15 of the TMZ cycle (assuming a standard regimen of 200 mg/m^2/day for 5 days of each 28-day cycle; for other TMZ schedules, timing of the depatuxizumab mafodotin dosing schedule were to be discussed with the medical monitor).
• Temozolomide
Capsules administered orally, 150 mg/m^2 on Days 1-5 for the first 28-day cycle, with dose escalation to 200 mg/m^2 in subsequent cycles in case of adequate tolerance until one of the treatment withdrawal criteria was met.
• Lomustine
Capsules administered orally, 110 mg/m^2 on Day 1 of every 42-day treatment period. Treatment continued until one of the treatment withdrawal criteria was met, for a maximum of one year.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital /ID# 135208	Adelaide	South Australia
Australia	Barwon Health University Hospital Geelong /ID# 134493	Geelong	Victoria
Australia	Royal Brisbane and Women's Hospital /ID# 147091	Herston	Queensland
Australia	Royal Hobart Hospital /ID# 135209	Hobart	Tasmania
Australia	Royal Children's Hospital /ID# 157624	Melbourne	Victoria
Australia	Port Macquarie Base Hospital /ID# 134569	Port Macquarie	New South Wales
Australia	Sydney Children's Hospital /ID# 153533	Randwick	New South Wales
Australia	Royal North Shore Hospital /ID# 147092	Saint Leonards	New South Wales
Australia	Calvary Mater Newcastle /ID# 134570	Waratah	New South Wales
Australia	Southern Medical Day Care Ctr /ID# 134495	Wollongong	New South Wales
Austria	LKH-Univ. Klinikum Graz /ID# 139071	Graz
Austria	Kepler Universitätsklinikum GmbH - Neuromed Campus /ID# 139068	Linz
Austria	University Hospital St. Polten /ID# 139070	St. Pölten	Niederoesterreich
Belgium	ZNA Middelheim /ID# 137926	Antwerp
Belgium	AZ St-Jan Brugge-Oostende AV /ID# 137927	Brugge	West-Vlaanderen
Belgium	Grand Hôpital de Charleroi /ID# 139342	Charleroi	Hainaut
Belgium	UZ Gent /ID# 152944	Gent	Oost-Vlaanderen
Belgium	UZ Leuven /ID# 137925	Leuven
Belgium	Cliniques Universitaires Saint Luc /ID# 139391	Woluwe-Saint-Lambert	Bruxelles-Capitale
Canada	Montreal Neurological Institut /ID# 136309	Montreal	Quebec
Czechia	Masarykuv onkologikcy ustav /ID# 139508	Brno
Czechia	FN Hradec Kralove /ID# 139510	Hradec Kralove
Czechia	Univ Hosp Ostrava-Poruba /ID# 139507	Ostrava
Czechia	Fakultni Nemocnice v Motole /ID# 139509	Prague 5	Praha 5
Finland	Helsinki Univ Central Hospital /ID# 140078	Helsinki
Finland	Helsinki Univ Central Hospital /ID# 153069	Helsinki
Finland	Turku University Hospital /ID# 140861	Turku
France	Institut de Cancer de l'Ouest /ID# 137909	Angers
France	CHU-Hopital Avicenne /ID# 137910	Bobigny	Ile-de-France
France	Hospices Civils de Lyon /ID# 137913	Bron
France	Centre Oscar Lambret /ID# 169619	Lille	Hauts-de-France
France	CHRU Lille - Hôpital Claude Huriez /ID# 137916	Lille CEDEX	Hauts-de-France
France	Centre Leon Berard /ID# 137918	Lyon CEDEX 08	Rhone
France	Hopital de la Timone /ID# 137911	Marseille CEDEX 05	Provence-Alpes-Cote-d Azur
France	CHU de Nice /ID# 137917	Nice CEDEX 1	Provence-Alpes-Cote-d Azur
France	Hopital Pitie Salpetriere /ID# 145887	Paris
France	Institut de Cancer de l'Ouest /ID# 137914	St Herblain CEDEX	Loire-Atlantique
France	Gustave Roussy /ID# 137912	Villejuif	Ile-de-France
Germany	Univ Klinik Eppendorf Hamburg /ID# 137921	Hamburg
Germany	Universitaetsklinik Heidelberg /ID# 137924	Heidelberg	Baden-Wuerttemberg
Germany	LMU Klinikum der Universität München /ID# 137922	Munich
Germany	Universitatsklinik Regensburg /ID# 137920	Ratisbon	Bayern
Germany	Universitatsklinikum Tubingen /ID# 137923	Tuebingen
Hungary	National Institute of Oncology /ID# 135970	Budapest
Hungary	Orszagos Klinikai Idegtudomany /ID# 135971	Budapest
Hungary	Semmelweis Egyetem /ID# 152578	Budapest
Hungary	Debreceni Egyetem Klinikai Központ /ID# 135969	Debrecen
Hungary	Pecsi Tudomanyegyetem /ID# 136111	Pécs	Pecs
Ireland	Cork University Hospital /ID# 136828	Cork
Ireland	Beaumont Hospital /ID# 136829	Dublin
Italy	Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 138335	Bologna
Italy	Ospedale Generale di Bolzano /ID# 138338	Bolzano
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 140395	Milan
Italy	Istituto Oncologico Veneto /ID# 138336	Padova
Italy	Azienda Ospedaliera Sant' Andrea /ID# 138337	Rome
Korea, Republic of	Seoul National Univ Bundang ho /ID# 136841	Seongnam	Gyeonggido
Korea, Republic of	Samsung Medical Center /ID# 136842	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital /ID# 136840	Seoul
Mexico	Hospital Zambrano Hellion /ID# 138076	San Pedro Garza García
Netherlands	Vrije Universiteit Medisch Centrum /ID# 137221	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen /ID# 138266	Groningen
Netherlands	Erasmus Medisch Centrum /ID# 136981	Rotterdam
Netherlands	Haaglanden Medisch Centrum /ID# 137222	The Hague
Netherlands	Prinses Maxima Centrum /ID# 204409	Utrecht
Netherlands	Universitair Medisch Centrum Utrecht /ID# 137219	Utrecht
Poland	Uniwersyteckie Centrum Kliniczne /ID# 137919	Gdansk	Mazowieckie
Poland	Wojewodzkie Wielospecjalistycz /ID# 137654	Lodz
Singapore	KK Women's & Children Hospital /ID# 153676	Singapore
Singapore	National Cancer Ctr Singapore /ID# 135952	Singapore
Singapore	National University Hospital /ID# 135951	Singapore
Spain	Instituto Catalán de Oncología (ICO) Badalona /ID# 140976	Badalona	Barcelona
Spain	Instituto Catalan de Oncologia (ICO) & Hosp. de Bellvitge /ID# 137688	Barcelona
Spain	Hosp Univ 12 de Octubre /ID# 137908	Madrid
Spain	Hospital Universitario Nino /ID# 153800	Madrid
Spain	Clinica Universitar de Navarra - Pamplona /ID# 140047	Pamplona	Navarra, Comunidad
Switzerland	Centre Hospitalier Univ Vaudoi /ID# 137929	Lausanne
Switzerland	University Hospital Zurich /ID# 137930	Zurich
Taiwan	China Medical University Hosp /ID# 136976	Taichung City	Taichung
Taiwan	Taichung Veterans General Hosp /ID# 136977	Taichung City
Taiwan	National Taiwan Univ Hosp /ID# 136975	Taipei City	Taipei
Taiwan	Taipei Veterans General Hosp /ID# 136974	Taipei City
Taiwan	Linkou Chang Gung Memorial Ho /ID# 136944	Taoyuan City
United Kingdom	Univ Hospitals Birmingham NHS Foundation trust /ID# 136978	Birmingham
United Kingdom	Gartnavel General Hospital /ID# 136979	Glasgow
United Kingdom	Hull and East Yorkshire NHS /ID# 136917	Hull
United Kingdom	Great Ormond St Hospital NHS /ID# 153421	London
United Kingdom	Guy's and St Thomas' NHS Found /ID# 140312	London	London, City Of
United Kingdom	University College Hospitals /ID# 136879	London
United Kingdom	Christie NHS Foundation Trust /ID# 140313	Manchester
United States	Children's Hospital Colorado /ID# 153677	Aurora	Colorado
United States	Univ of Colorado Cancer Center /ID# 134882	Aurora	Colorado
United States	Dana-Farber Cancer Institute /ID# 154210	Boston	Massachusetts
United States	Rush University Medical Center /ID# 137542	Chicago	Illinois
United States	Cleveland Clinic Main Campus /ID# 137540	Cleveland	Ohio
United States	UT Southwestern Medical Center /ID# 136718	Dallas	Texas
United States	Sarah Cannon Research Institute at HealthONE - Denver /ID# 141798	Denver	Colorado
United States	Long Island Brain Tumor Center /ID# 134496	Lake Success	New York
United States	Tennessee Oncology, PLLC /ID# 134492	Nashville	Tennessee
United States	Weill Cornell Medicine /ID# 152656	New York	New York
United States	Lucile Packard Children's Hosp /ID# 153678	Palo Alto	California
United States	University of Pittsburgh MC /ID# 134491	Pittsburgh	Pennsylvania
United States	Swedish Medical Center /ID# 136719	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Finland,  France,  Germany,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Singapore,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adult Study: Overall Survival (OS)	Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine).	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.
Primary	Adult Study: Progression-Free Survival (PFS)	Progression-free survival was assessed per response assessment in neuro-oncology criteria (RANO) criteria and assessed by an independent review committee and was defined as the length of time during and after the treatment of a disease, that the participant lived with the disease but did not get worse.	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
Primary	Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug	The severity of each adverse event was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0)	From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks
Primary	Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414	Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.	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
Primary	Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose. Cys-mcMMAF is a toxic metabolite of depatuxizumab mafodotin.	Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Primary	Pediatric Study: Half-life (t1/2) Observed for ABT-414	Half-life is the calculated time it takes for half of the drug to leave the body.	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
Primary	Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF	Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body. CysmcMMAF is a toxic metabolite of depatuxizumab mafodotin.	Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Primary	Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414	AUC is a measure of how long and how much drug is present in the body after dosing. The AUC of depatuxizumab mafodotin (ABT-414) in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.	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
Primary	Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF	AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. The AUC of Cys-mcMMAF, a toxic metabolite of depatuxizumab mafodotin, in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.	Samples collected Cycle 1 Days 1, 2, 3, 5, 8
Secondary	Adult Study: Objective Response Rate (ORR)	The objective response rate (ORR) included best overall responses - complete response (CR) and partial response (PR) - assessed by the independent review committee per response assessment in neurooncology criteria (RANO) criteria from the date of randomization until disease progression or death, whichever came first. All objective responses (CR and PR) must be have been confirmed by repeat MRI 4 weeks after the first time when CR or PR is identified. Any subject who did not meet CR or PR including those who did not have post-baseline radiological assessments was considered a nonresponder.	Every 8 weeks at each assessment of disease, up to 28 months
Secondary	Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation	Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine) for all randomized participants that had the Epidermal Growth Factor Receptor (EGFRvIII) mutation.	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
Secondary	Pediatric Study: Objective Response Rate (ORR)	The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.	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
Secondary	Pediatric Study: Best Tumor Response Rate	The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.	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
Secondary	Pediatric Study: Duration of Response	The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.	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
Secondary	Pediatric Study: Overall Survival	The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.	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
Secondary	Pediatric Study: Time to Progression	The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/ temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, pediatric time to progression data analysis was not summarized due to the small number of pediatric participants enrolled in the study.	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
Secondary	Pediatric Study: Progression-Free Survival	The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.	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
Secondary	Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning	The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.	Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually