Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Depatuxizumab, Mafodotin, Depatuxizumab Mafodotin
ABT-414 · 5 trials · 5 indications
Time to OS is defined as the number of days from the date of randomization to the date of death due to any cause.
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).
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.
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)
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.
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.
Half-life is the calculated time it takes for half of the drug to leave the body.
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.
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.
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.
Measurement by clinical lab results, vital signs, physical exam and electrocardiogram (ECG) during the Phase 1 portion of the study.
Time to progression-free survival is defined as the number of days from the date of first dose to the date of earliest disease progression based on Response Assessment in Neuro-Oncology (RANO) criteria or to the date of death, if disease progression does not occur (except Arm B and Arm C of Phase 1 portion).
Assessed during the Phase 1 portion of the study, the area under the plasma concentration-time curve (AUC) is a method of measurement to determine the total exposure of a drug in blood plasma.
Assessed during the Phase 1 portion of the study, the maximum plasma concentration (Cmax) is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Measurement by clinical lab results, vital signs, physical exam, and electrocardiogram (ECG)
Measurement of the maximum concentration of ABT- 414 in the blood
Measurement of the minimum concentration of ABT-414 in the blood
Measurement of the clearance of ABT-414
Evaluation of vital signs, clinical lab testing, adverse event monitoring, physical exam and electrocardiogram (ECG) (periodic) under different dosing schedules, drug infusion times, and manufacturing processes.
Cmax, Cmin, and half-life
Objective response per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST)
| Arm | Type | Description |
|---|---|---|
| Depatuxizumab Mafodotin, Radiation and Temozolomide (TMZ) | EXPERIMENTAL | Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. |
| Placebo, Radiation and TMZ | PLACEBO_COMPARATOR | Placebo is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Placebo is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. |
| Open-Label Sub-Study: Depatuxizumab Mafodotin, Radiation and TMZ | EXPERIMENTAL | Depatuxizumab mafodotin is given to participants with hepatic impairment on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase. |
| ABT-414/temozolomide | EXPERIMENTAL | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants |
| ABT-414_adult | EXPERIMENTAL | Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants |
| Control_lomustine | ACTIVE_COMPARATOR | 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. |
| Control_ temozolomide | ACTIVE_COMPARATOR | 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. |
| ABT-414_ pediatric | EXPERIMENTAL | 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). |
| Arm A of Phase 1 portion | EXPERIMENTAL | ABT-414 administered every other weeks monotherapy |
| Phase 2 portion | EXPERIMENTAL | ABT-414 administered every other weeks in combination with temozolomide |
| Arm C of Phase 1 portion | EXPERIMENTAL | ABT-414 administered every other weeks in combination with radiation and temozolomide |
| Arm B of Phase 1 portion | EXPERIMENTAL | ABT-414 administered every other weeks in combination with radiation and temozolomide |
| Arm A | EXPERIMENTAL | ABT-414 in combination with radiation and temozolomide |
| Arm B | EXPERIMENTAL | ABT-414 in combination with temozolomide |
| Arm C | EXPERIMENTAL | ABT-414 monotherapy |
| ABT-414 | EXPERIMENTAL | Subjects with solid tumors (Phase 1) and squamous non-small cell lung cancer (NSCLC) (Phase 2) |
| Name | Type | Description |
|---|---|---|
| Temozolomide | DRUG | Oral Capsule |
| Depatuxizumab mafodotin | DRUG | Intravenous (IV) Infusion |
| Radiation | RADIATION | - |
| Placebo for ABT-414 | DRUG | IV Infusion (IV) |
| Lomustine | DRUG | 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. |
| Whole Brain Radiation | RADIATION | Whole Brain Radiation will be administered in over 30 fractions as per the procedure in each study site. |
| ABT-414 | DRUG | ABT-414 will be administered by intravenous infusion |
Inclusion Criteria: * Must have a clinical diagnosis of glioblastoma (GBM). * Must have a confirmed epidermal growth factor receptor amplification in tumor tissue. * Must have a Karnofsky Performance Status (KPS) \>= 70 at assessment \<= 14 days prior to randomization (N/A to the sub-study). * Must...
ABT-414 is an investigational therapy studied for glioblastoma multiforme, malignant glioma, and squamous cell tumors. It has been evaluated in Phase 1 clinical trials in adults with these cancers, including a dedicated study in Japanese subjects with malignant glioma. It is not an approved treatment.
ABT-414 is being developed by AbbVie Inc., which trades on the New York Stock Exchange under the ticker ABBV. AbbVie sponsored the Phase 1 clinical program evaluating the agent in glioblastoma multiforme, malignant glioma, and squamous cell tumors.
ABT-414 is in Phase 1 clinical development. All three of its recorded trials are Phase 1 studies, and all have been completed. The program enrolled 202 subjects in its largest glioblastoma multiforme study, with additional Phase 1 studies in Japanese malignant glioma patients and in solid tumors.
ABT-414 has been studied in three completed Phase 1 trials: NCT01800695 in glioblastoma multiforme, NCT02590263 in Japanese subjects with malignant glioma, and NCT01741727 in squamous cell tumors. The squamous cell tumor study was conducted in the United States and Canada.
Yes, ABT-414 trials used biomarker-based patient selection. The clinical program enrolled adults with glioblastoma multiforme, malignant glioma, and squamous cell tumors, with eligibility tied to biomarker criteria rather than an unselected patient population.
The ABT-414 clinical program enrolled patients across three completed Phase 1 studies. The largest, NCT01800695 in glioblastoma multiforme, enrolled 202 subjects. NCT01741727 in squamous cell tumors enrolled 57, and NCT02590263 in Japanese malignant glioma patients enrolled 53.