The objective of this study was to evaluate the effect of several ophthalmologic prophylactic treatment strategies for the management of ocular side effects (OSEs) in participants with epidermal growth factor receptor (EGFR)-amplified glioblastoma (GBM) who were being treated with depatuxizumab mafodotin (ABT-414).
This Phase 3b open-label, randomized, exploratory study included 2 phases during the treatment period: chemoradiation therapy (radiation plus temozolomide \[RT/TMZ\]) and adjuvant therapy (TMZ). All participants received depatuxizumab mafodotin during both phases of the treatment period plus 1 of 3 prophylactic ophthalmologic treatments (standard steroids; standard steroids with vasoconstrictors and cold compress; and enhanced steroids with vasoconstrictors and cold compress. The study comprised a screening period of up to 7 weeks after surgery, a 6-week concomitant Chemoradiation Phase, an Adjuvant Phase beginning approximately 4 weeks after completion of chemoradiation, and a Follow-Up Phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Usc /Id# 164235
Los Angeles, California, United States
Percentage of Participants Who Required a Change in Ocular Side Effect (OSE) Management
Inadequate control of ocular side effects (OSE) was defined as either a ≥ 3-line decline from baseline (≥ +0.3 on LogMAR scale) in visual acuity (with baseline correction determined at the screening ophthalmology visit)) or ≥ Grade 3 OSE severity on the Corneal Epithelial Adverse Event (CEAE) scale.
Time frame: Within 8 weeks after the initial dose of depatuxizumab mafodotin
Maximum Change From Baseline on the Logarithm of the Minimum Angle of Resolution (LogMAR) Scale
The LogMAR scale measures visual acuity on a continuous scale, with a LogMAR value of 0 equivalent to 20/20 visual acuity. Normal vision is considered to be from -0.2 - 0.1; higher values indicate visual impairment. The baseline observation is defined as the last non-missing measurement collected prior to the first dose of depatuxizumab mafodotin.
Time frame: Within 8 weeks after the initial dose of depatuxizumab mafodotin
Time to Bandage Contact Lens (BCL) Intervention
The time to initiation of bandage contact lenses for those participants who required intervention due to inadequate control of ocular side effects (OSE) was calculated.
Time frame: Up to 9 months after the first dose of depatuxizumab mafodotin
Number of Participants With Depatuxizumab Mafodotin Dose Modifications Due to Ocular Side Effects (OSE)
Dose modifications included depatuxizumab mafodotin withdrawal, interruption, and reductions in dose initiated due to OSEs.
Time frame: From the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks
Cumulative Dose of Depatuxizumab Mafodotin Received During Chemoradiation and During Adjuvant Treatment
The cumulative dose of depatuxizumab mafodotin administered was tabulated.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Ointment
During the Chemoradiation Phase, participants were to receive depatuxizumab mafodotin at 2.0 mg/kg IV infusion over 30 - 40 minutes once every 2 weeks (Day 1 of Weeks 1, 3, and 5 of the 6-week regimen). During the Adjuvant Therapy Phase, participants were to receive depatuxizumab mafodotin at 1.25 mg/kg on Day 1 (± 2 days) and Day 15 (± 2 days) of each 28-day cycle as a 30 - 40 minute infusion for 12 cycles.
Temozolomide was to be administered according to the local standard of care. Duration of treatment was to be 6 - 12 cycles in the adjuvant phase and at the discretion of the investigator as supported by local standard of care.
Radiation therapy treatment planning and administration was to be performed as per local institutional guidelines.
Moffitt Cancer Center /ID# 164234
Tampa, Florida, United States
Rush University Medical Center /ID# 171003
Chicago, Illinois, United States
Northshore University Health System-Evanston /ID# 164221
Evanston, Illinois, United States
CDH-Delnor Health System /ID# 169909
Warrenville, Illinois, United States
Columbia University Medical Center /ID# 164220
New York, New York, United States
Levine Cancer Ins, Carolina Me /ID# 171271
Charlotte, North Carolina, United States
UT Health Science Ctr-Houston /ID# 164223
Houston, Texas, United States
Baylor Scott & White Medical Center- Temple /ID# 170792
Temple, Texas, United States
Royal North Shore Hospital /ID# 169673
Saint Leonards, New South Wales, Australia
...and 12 more locations
Time frame: Up to 9 months
Treatment-Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit
The corneal epithelial adverse event (CEAE) rating scale is designed to record symptoms associated with corneal epitheliopathy caused by antibody-drug conjugates and to grade the severity of findings. The overall CEAE grade is measured on a scale of 0 to 5, with higher values being more severe, reflecting the impact of corneal abnormalities on visual activities of daily living (ADLs). Additional detailed information is collected for specific domains that are commonly affected, with the following ranges (each in order of increasing severity): ocular discomfort (0 - 4), photophobia (0 - 3), and reading (1 - 3).
Time frame: Up to 47 weeks
Change From Baseline In Logarithm of the Minimum Angle of Resolution (LogMAR) Scale After Bandage Contact Lens (BCL) Intervention
The change on the LogMAR Scale from last assessment prior to BCL intervention to 2 weeks after BCL intervention was calculated. The LogMAR scale measures visual acuity on a continuous scale, with a LogMAR value of 0 equivalent to 20/20 visual acuity. Normal vision is considered to be from -0.2 - 0.1; higher values indicate visual impairment.
Time frame: From the last assessment prior to BCL intervention to 2 weeks after BCL intervention
Percentage of Participants That Recovered to <3-line Decline From Baseline (≤ +0.3 LogMAR) in Visual Acuity After Bandage Contact Lens (BCL) Intervention
Recovery was defined as return to \<3-line decline from baseline (≤ +0.3 LogMAR) in visual acuity after BCL intervention.
Time frame: From the last assessment prior to BCL intervention to the end of BCL intervention
Number of Participants With Depatuxizumab Mafodotin Dose Modifications to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention
Dose modifications included depatuxizumab mafodotin withdrawal, interruption, and reductions in dose initiated due to OSEs after BCL intervention.
Time frame: From the last assessment prior to BCL intervention to the end of BCL intervention, up to 38 weeks
Time to Restart Depatuxizumab Mafodotin if Interrupted Due to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention
The time to restart depatuxizumab mafodotin treatment if it was interrupted due to ocular side effects after BCL Intervention was tabulated.
Time frame: From the last assessment prior to BCL intervention to the end of BCL intervention
Treatment Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit After Bandage Contact Lens (BCL) Intervention
The corneal epithelial adverse event (CEAE) rating scale is designed to record symptoms associated with corneal epitheliopathy caused by antibody-drug conjugates and to grade the severity of findings. The overall CEAE grade is measured on a scale of 0 to 5, with higher values being more severe, reflecting the impact of corneal abnormalities on visual activities of daily living (ADLs). Additional detailed information is collected for specific domains that are commonly affected, with the following ranges (each in order of increasing severity): ocular discomfort (0 - 4), photophobia (0 - 3), and reading (1 - 3).
Time frame: From the last assessment prior to BCL intervention to the end of BCL intervention, up to 38 weeks
Time to Ocular Side Effect (OSE) Symptom Resolution After Drug Discontinuation (Reversibility)
The time from discontinuation of depatuxizumab mafodotin to OSE symptom resolution (reversibility) was to be recorded.
Time frame: From the first dose of study drug until 49 days after last depatuxizumab mafodotin administration, up to 47 weeks
Time to Re-initiation of Depatuxizumab Mafodotin After Dose Interruption
The time from dose interruption until re-initiation or permanent discontinuation of depatuxizumab mafodotin was to be recorded.
Time frame: Up to 9 months