A Phase IIb/III study of ABT-414 for newly diagnosed glioblastoma
Research type
Research Study
Full title
A Randomized, Placebo Controlled Phase 2b/3 Study of ABT-414 with Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects with Newly Diagnosed Glioblastoma (GBM) with Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance 1)
IRAS ID
184545
Contact name
Clare Murphy
Contact email
Sponsor organisation
AbbVie Ltd.
Eudract number
2015-001166-26
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
3508, RTOG protocol reference number
Duration of Study in the UK
4 years, 4 months, 22 days
Research summary
Research Summary
Glioblastoma is the most common and aggressive form of primary brain tumour. Around 2,200 cases are diagnosed each year in England; survival rates are extremely poor. The standard first line treatment is radiotherapy with chemotherapy (temozolomide) given at the same time and then alone following the radiotherapy: average survival times with treatment are 14.6 months.
Temozolomide and radiotherapy treat the cancer by damaging the genetic material of the tumour. ABT-414 is a new drug which delivers another toxic chemical (monomethylauristatin F) into glioblastoma cells with a marker (an “activated” protein called EGFR) on the outside. An earlier study has suggested a beneficial effect in patients whose tumours are producing more EGFR (amplification).
In this study half of patients will receive infusions every two weeks of ABT-414 alongside and after the standard treatment, and the other half will receive placebo (dummy) infusions alongside and after the standard treatment. The trial will determine which treatment is better at controlling the cancer, by measuring progression-free and survival time. This is a Phase IIb/III, randomised, double blind trial (neither patients nor their doctors will know which treatments they are receiving).
Patients could benefit if tumour growth is inhibited, improving their condition and survival time. Information gathered may help improve future treatment.
Patients will first have a tumour sample tested for EGFR amplification; if present they may be eligible to join the trial.
They will attend regular study visits at hospital and have treatment for as long as they are benefiting. The effect of treatments on the cancer will be checked by having brain scans, blood tests, checking for side effects and completing questionnaires and assessments. There are additional blood tests to see why some people respond better than others, how long the drug remains in the body, and optional genetics tests and tissue donation.
Summary of results
• Glioblastoma (GBM) is the most common and deadliest form of brain cancer.
• Treatment options are limited, and long-term treatment is not available.
• Some patients with GBM have epidermal growth factor receptor (EGFR) amplifiction.
• EGFR is a receptor in the cells. When it is amplifid
(increased) it can cause fast cell growth which leads to poor outcomes for patients.
• In this study, patients with newly diagnosed GBM with EGFR amplifiction were treated with depatuxizumab mafodotin (Depatux-M) in addition to standard of care treatment with radiation therapy (RT) and a chemotherapy medicine called temozolomide (TMZ).
• This study took place from January 2015 to April 2022 in 28 countries.
• The main goal of the study was to learn whether adding Depatux-M to RT and TMZ changed the length of overall survival (OS) for patients with GBM.
• OS is the length of time patients are still alive after the start of the study treatment.
• The main study had two treatment periods. In Period 1, patients were randomly (by chance) placed into one of two groups to receive placebo (Group 1) or Depatux-M (Group 2) in addition to their standard treatment with RT and TMZ.
• In the Period 2, patients received either placebo (Group 1) or Depatux-M (Group 2) in addition to TMZ.
• This study also included a small substudy of patients with GBM that also had reduced (lowered) liver function due to chronic liver disease or cirrhosis (scarring) of the liver.
• In the substudy, all patients (Group 3) received Depatux-M plus RT and TMZ in Period 1 followed by Depatux-M and TMZ in Period 2.
• The main study showed that there was no improvement in survival for patients treated with Depatux-M + RT and TMZ compared to patients treated with placebo + RT and TMZ.
• Because no survival benefit as seen, the study was ended early by the Sponsor.
• 91.4% of patients in Group 1 and 98.5% of patients in Group 2 had side efects during the main study.
100.0% of patients in Group 3 had side efects during the substudy. Side efects are medical events considered by the study doctors to be at least possibly related to the study treatment.
• The most common side efects were nausea and tiredness in Group 1, keratopathy (damage to the outer layer of the eye) and thrombocytopenia (large decrease in platelets in the blood, which help stop bleeding) in Group 2 and Group 3.
• Depatux-M is no longer being developed for use at this time.
• If you participated in this study and have questions about your individual care, contact the doctor or staff t your study site.REC name
London - Dulwich Research Ethics Committee
REC reference
15/LO/1950
Date of REC Opinion
4 Jan 2016
REC opinion
Further Information Favourable Opinion