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 (INTELLANCE-2)

• ClinicalTrials.gov Identifier: NCT02343406
• Recruitment Status: Completed
• First Posted: January 22, 2015
• Results First Posted: May 22, 2020
• Last Update Posted: May 22, 2020
• Sponsor: AbbVie
• Collaborator: European Organisation for Research and Treatment of Cancer - EORTC
• Information provided by (Responsible Party): AbbVie

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Glioblastoma	Drug: Depatuxizumab mafodotin; Drug: Temozolomide; Drug: Lomustine	Phase 2

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 The EMEA-001732-PIP02-15 pediatric investigation plan was withdrawn on 07 July 2019 due to the discontinuation of the depatuxizumab mafodotin research program.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 266 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 17, 2015
• Actual Primary Completion Date: June 24, 2019
• Actual Study Completion Date: June 24, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: ABT-414/temozolomide; Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants	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).; Other Name: ABT-414; Drug: 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.; Other Name: TMZ
Experimental: ABT-414_adult; Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants	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).; Other Name: ABT-414
Active Comparator: Control_lomustine; Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year.	Drug: 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.; Other Name: Gleostine
Active Comparator: Control_ temozolomide; Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met.	Drug: 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.; Other Name: TMZ
Experimental: ABT-414_ pediatric; Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).	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).; Other Name: ABT-414

Outcome Measures

Primary Outcome Measures :

1. Adult Study: Overall Survival (OS) [ Time Frame: 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. ]
   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).
2. Adult Study: Progression-Free Survival (PFS) [ Time Frame: 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 ]
   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.
3. Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug [ Time Frame: From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks ]
   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)
4. Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414 [ Time Frame: 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 ]
   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.
5. Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
   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.
6. Pediatric Study: Half-life (t1/2) Observed for ABT-414 [ Time Frame: 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 ]
   Half-life is the calculated time it takes for half of the drug to leave the body.
7. Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
   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.
8. Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414 [ Time Frame: 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 ]
   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.
9. Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF [ Time Frame: Samples collected Cycle 1 Days 1, 2, 3, 5, 8 ]
   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.

Secondary Outcome Measures :

1. Adult Study: Objective Response Rate (ORR) [ Time Frame: Every 8 weeks at each assessment of disease, up to 28 months ]
   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.
2. Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation [ Time Frame: 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 ]
   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.
3. Pediatric Study: Objective Response Rate (ORR) [ Time Frame: 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 ]
   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.
4. Pediatric Study: Best Tumor Response Rate [ Time Frame: 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 ]
   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.
5. Pediatric Study: Duration of Response [ Time Frame: 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 ]
   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.
6. Pediatric Study: Overall Survival [ Time Frame: 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 ]
   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.
7. Pediatric Study: Time to Progression [ Time Frame: 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 ]
   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.
8. Pediatric Study: Progression-Free Survival [ Time Frame: 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 ]
   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.
9. Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning [ Time Frame: Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually ]
   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.

Eligibility Criteria

• Ages Eligible for Study: up to 99 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Lucile Packard Children's Hosp /ID# 153678

Palo Alto, California, United States, 34304

United States, Colorado

Children's Hospital Colorado /ID# 153677

Aurora, Colorado, United States, 80045

Univ of Colorado Cancer Center /ID# 134882

Aurora, Colorado, United States, 80045

Sarah Cannon Research Institute at HealthONE - Denver /ID# 141798

Denver, Colorado, United States, 80218

United States, Illinois

Rush University Medical Center /ID# 137542

Chicago, Illinois, United States, 60612

United States, Massachusetts

Dana-Farber Cancer Institute /ID# 154210

Boston, Massachusetts, United States, 02215

United States, New York

Long Island Brain Tumor Center /ID# 134496

Lake Success, New York, United States, 11042

Weill Cornell Medicine /ID# 152656

New York, New York, United States, 10032-3725

United States, Ohio

Cleveland Clinic Main Campus /ID# 137540

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

University of Pittsburgh MC /ID# 134491

Pittsburgh, Pennsylvania, United States, 15260

United States, Tennessee

Tennessee Oncology, PLLC /ID# 134492

Nashville, Tennessee, United States, 37203

United States, Texas

UT Southwestern Medical Center /ID# 136718

Dallas, Texas, United States, 75390-7208

United States, Washington

Swedish Medical Center /ID# 136719

Seattle, Washington, United States, 98104

Australia, New South Wales

Port Macquarie Base Hospital /ID# 134569

Port Macquarie, New South Wales, Australia, 2444

Sydney Children's Hospital /ID# 153533

Randwick, New South Wales, Australia, 2031

Royal North Shore Hospital /ID# 147092

Saint Leonards, New South Wales, Australia, 2065

Calvary Mater Newcastle /ID# 134570

Waratah, New South Wales, Australia, 2298

Southern Medical Day Care Ctr /ID# 134495

Wollongong, New South Wales, Australia, 2500

Australia, Queensland

Royal Brisbane and Women's Hospital /ID# 147091

Herston, Queensland, Australia, 4029

Australia, South Australia

Royal Adelaide Hospital /ID# 135208

Adelaide, South Australia, Australia, 5000

Australia, Tasmania

Royal Hobart Hospital /ID# 135209

Hobart, Tasmania, Australia, 7000

Australia, Victoria

Barwon Health University Hospital Geelong /ID# 134493

Geelong, Victoria, Australia, 3220

Royal Children's Hospital /ID# 157624

Melbourne, Victoria, Australia, 3052

Austria

University Hospital St. Polten /ID# 139070

St. Pölten, Niederoesterreich, Austria, 3100

LKH-Univ. Klinikum Graz /ID# 139071

Graz, Austria, 8036

Kepler Universitätsklinikum GmbH - Neuromed Campus /ID# 139068

Linz, Austria, 4020

Belgium

Cliniques Universitaires Saint Luc /ID# 139391

Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium, 1200

Grand Hôpital de Charleroi /ID# 139342

Charleroi, Hainaut, Belgium, 6000

UZ Gent /ID# 152944

Gent, Oost-Vlaanderen, Belgium, 9000

AZ St-Jan Brugge-Oostende AV /ID# 137927

Brugge, West-Vlaanderen, Belgium, 8000

ZNA Middelheim /ID# 137926

Antwerp, Belgium, 2020

UZ Leuven /ID# 137925

Leuven, Belgium, 3000

Canada, Quebec

Montreal Neurological Institut /ID# 136309

Montreal, Quebec, Canada, H3A 2B4

Czechia

Fakultni Nemocnice v Motole /ID# 139509

Prague 5, Praha 5, Czechia, 150 06

Masarykuv onkologikcy ustav /ID# 139508

Brno, Czechia, 656 53

FN Hradec Kralove /ID# 139510

Hradec Kralove, Czechia, 500 05

Univ Hosp Ostrava-Poruba /ID# 139507

Ostrava, Czechia, 708 52

Finland

Helsinki Univ Central Hospital /ID# 140078

Helsinki, Finland, 00290

Helsinki Univ Central Hospital /ID# 153069

Helsinki, Finland, 00290

Turku University Hospital /ID# 140861

Turku, Finland, 20520

France

CHRU Lille - Hôpital Claude Huriez /ID# 137916

Lille CEDEX, Hauts-de-France, France, 59045

Centre Oscar Lambret /ID# 169619

Lille, Hauts-de-France, France, 59020

CHU-Hopital Avicenne /ID# 137910

Bobigny, Ile-de-France, France, 93000

Gustave Roussy /ID# 137912

Villejuif, Ile-de-France, France, 94805

Institut de Cancer de l'Ouest /ID# 137914

St Herblain CEDEX, Loire-Atlantique, France, 44805

Hopital de la Timone /ID# 137911

Marseille CEDEX 05, Provence-Alpes-Cote-d Azur, France, 13385

CHU de Nice /ID# 137917

Nice CEDEX 1, Provence-Alpes-Cote-d Azur, France, 06002

Centre Leon Berard /ID# 137918

Lyon CEDEX 08, Rhone, France, 69373

Institut de Cancer de l'Ouest /ID# 137909

Angers, France, 49055

Hospices Civils de Lyon /ID# 137913

Bron, France, 69500

Hopital Pitie Salpetriere /ID# 145887

Paris, France, 75651

Germany

Universitaetsklinik Heidelberg /ID# 137924

Heidelberg, Baden-Wuerttemberg, Germany, 69120

Universitatsklinik Regensburg /ID# 137920

Ratisbon, Bayern, Germany, 93053

Univ Klinik Eppendorf Hamburg /ID# 137921

Hamburg, Germany, 20246

LMU Klinikum der Universität München /ID# 137922

Munich, Germany, 80337

Universitatsklinikum Tubingen /ID# 137923

Tuebingen, Germany, 72076

Hungary

Pecsi Tudomanyegyetem /ID# 136111

Pécs, Pecs, Hungary, 7624

Semmelweis Egyetem /ID# 152578

Budapest, Hungary, 1085

National Institute of Oncology /ID# 135970

Budapest, Hungary, 1122

Orszagos Klinikai Idegtudomany /ID# 135971

Budapest, Hungary, 1145

Debreceni Egyetem Klinikai Központ /ID# 135969

Debrecen, Hungary, 4032

Ireland

Cork University Hospital /ID# 136828

Cork, Ireland, T12 E8YV

Beaumont Hospital /ID# 136829

Dublin, Ireland, D09 XR63

Italy

Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 138335

Bologna, Italy, 40139

Ospedale Generale di Bolzano /ID# 138338

Bolzano, Italy, 39100

Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 140395

Milan, Italy, 20133

Istituto Oncologico Veneto /ID# 138336

Padova, Italy, 35128

Azienda Ospedaliera Sant' Andrea /ID# 138337

Rome, Italy, 00189

Korea, Republic of

Seoul National Univ Bundang ho /ID# 136841

Seongnam, Gyeonggido, Korea, Republic of, 13620

Samsung Medical Center /ID# 136842

Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351

Seoul National University Hospital /ID# 136840

Seoul, Korea, Republic of, 03080

Mexico

Hospital Zambrano Hellion /ID# 138076

San Pedro Garza García, Mexico, 66278

Netherlands

Vrije Universiteit Medisch Centrum /ID# 137221

Amsterdam, Netherlands, 1081 HV

Universitair Medisch Centrum Groningen /ID# 138266

Groningen, Netherlands, 9713 GZ

Erasmus Medisch Centrum /ID# 136981

Rotterdam, Netherlands, 3015 CE

Haaglanden Medisch Centrum /ID# 137222

The Hague, Netherlands, 2512 VA

Universitair Medisch Centrum Utrecht /ID# 137219

Utrecht, Netherlands, 3584 CX

Prinses Maxima Centrum /ID# 204409

Utrecht, Netherlands, 3584 EA

Poland

Uniwersyteckie Centrum Kliniczne /ID# 137919

Gdansk, Mazowieckie, Poland, 80-214

Wojewodzkie Wielospecjalistycz /ID# 137654

Lodz, Poland, 93-509

Singapore

National University Hospital /ID# 135951

Singapore, Singapore, 119074

National Cancer Ctr Singapore /ID# 135952

Singapore, Singapore, 169610

KK Women's & Children Hospital /ID# 153676

Singapore, Singapore, 229899

Spain

Instituto Catalán de Oncología (ICO) Badalona /ID# 140976

Badalona, Barcelona, Spain, 08916

Clinica Universitar de Navarra - Pamplona /ID# 140047

Pamplona, Navarra, Comunidad, Spain, 31008

Instituto Catalan de Oncologia (ICO) & Hosp. de Bellvitge /ID# 137688

Barcelona, Spain, 08908

Hospital Universitario Nino /ID# 153800

Madrid, Spain, 28009

Hosp Univ 12 de Octubre /ID# 137908

Madrid, Spain, 28041

Switzerland

Centre Hospitalier Univ Vaudoi /ID# 137929

Lausanne, Switzerland, 1011

University Hospital Zurich /ID# 137930

Zurich, Switzerland, 8091

Taiwan

China Medical University Hosp /ID# 136976

Taichung City, Taichung, Taiwan, 40447

National Taiwan Univ Hosp /ID# 136975

Taipei City, Taipei, Taiwan, 10002

Taichung Veterans General Hosp /ID# 136977

Taichung City, Taiwan, 40705

Taipei Veterans General Hosp /ID# 136974

Taipei City, Taiwan, 11217

Linkou Chang Gung Memorial Ho /ID# 136944

Taoyuan City, Taiwan, 33305

United Kingdom

Guy's and St Thomas' NHS Found /ID# 140312

London, London, City Of, United Kingdom, SE1 9RT

Univ Hospitals Birmingham NHS Foundation trust /ID# 136978

Birmingham, United Kingdom, B15 2TG

Gartnavel General Hospital /ID# 136979

Glasgow, United Kingdom, G12 0YN

Hull and East Yorkshire NHS /ID# 136917

Hull, United Kingdom, HU8 9HE

University College Hospitals /ID# 136879

London, United Kingdom, NW1 2BU

Great Ormond St Hospital NHS /ID# 153421

London, United Kingdom, WC1N 3JH

Christie NHS Foundation Trust /ID# 140313

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

AbbVie

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

• Study Director: AbbVie Inc.; AbbVie

  Study Documents (Full-Text)

Documents provided by AbbVie:

Study Protocol  [PDF] January 4, 2019

Statistical Analysis Plan  [PDF] May 24, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Erratum In: Neuro Oncol. 2021 Aug 2;23(8):1415.

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.

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.

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.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02343406
• Other Study ID Numbers: M14-483; 2014-004438-24 ( EudraCT Number ); EORTC 1410-BTG ( Other Grant/Funding Number: European Organization for Research and Treatment of Cancer )
• First Posted: January 22, 2015
• Results First Posted: May 22, 2020
• Last Update Posted: May 22, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:

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

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Temozolomide; Lomustine; ABT-414; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunoconjugates; Immunologic Factors; Physiological Effects of Drugs