Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Vasoconstrictor Agents

Temozolomide

Ophthalmic Solutions

Mitogens

ABT-414

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunoconjugates

Immunologic Factors

Steroid eye drops: 1 drop each eye, 3 times/day, starting 2 days prior to depatuxizumab mafodotin infusion and continuing until 4 days after infusion, for a total of 7 days

Steroid eye drops: 1 drop each eye, 3 times/day, starting 2 days prior to depatuxizumab mafodotin infusion and continuing until 4 days after infusion, for a total of 7 days; Vasoconstrictor Eye Drops: 1 drop each eye 4 - 6 times on day of infusion in total (5 - 10 minutes before infusion; at end of infusion; and 2 - 4 times during the remainder of the infusion day). Continuing 4 - 6 times/day on Day 1 and Day 2 after each depatuxizumab mafodotin infusion; Cold Compress: Starting 5 minutes prior to start of infusion and continuing for 30 minutes past end of infusion, and then use at least 2 hours total/day on Days 1 - 3 with each depatuxizumab mafodotin infusion. The cold compress was to be applied in increments no longer than 30 min (could be shorter if the participant was uncomfortable).

Enhanced steroid eye drops: 1 drop each eye, 6 times/day, starting 2 days prior to depatuxizumab mafodotin infusion and continuing until 4 days after infusion, for a total of 7 days; Ophthalmic Steroid Ointment; applied to each eye once daily before sleep, starting 2 days prior to depatuxizumab mafodotin infusion and continuing until 4 days after infusion, for a total of 7 days; Vasoconstrictor Eye Drops: 1 drop each eye 4 - 6 times on day of infusion in total (5 - 10 minutes before infusion; at end of infusion; and 2 - 4 times during the remainder of the infusion day). Continuing 4 - 6 times/day on Day 1 and Day 2 after each depatuxizumab mafodotin infusion; Cold Compress: Starting 5 minutes prior to start of infusion and continuing for 30 minutes past end of infusion, and then use at least 2 hours total/day on Days 1 - 3 with each depatuxizumab mafodotin infusion. Cold compress was to be applied in increments no longer than 30 min (could be shorter if the patient is uncomfortable).

Steroid eye drops

Vasoconstrictor eye drops

Cold compress

Ophthalmic steroid 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.

Depatuxizumab mafodotin

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.

Radiation

AbbVie Inc.

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.

UNITE Study: Understanding New Interventions With GBM ThErapy

Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)

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.

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.

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.

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.

Dose modifications included depatuxizumab mafodotin withdrawal, interruption, and reductions in dose initiated due to OSEs.

The cumulative dose of depatuxizumab mafodotin administered was tabulated.

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).

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.

Recovery was defined as return to \<3-line decline from baseline (≤ +0.3 LogMAR) in visual acuity after BCL intervention.

Dose modifications included depatuxizumab mafodotin withdrawal, interruption, and reductions in dose initiated due to OSEs after BCL intervention.

The time to restart depatuxizumab mafodotin treatment if it was interrupted due to ocular side effects after BCL Intervention was tabulated.

The time from discontinuation of depatuxizumab mafodotin to OSE symptom resolution (reversibility) was to be recorded.

The time from dose interruption until re-initiation or permanent discontinuation of depatuxizumab mafodotin was to be recorded.

AbbVie

TEAEs and SAEs are defined as any AE or SAE with onset or worsening reported by a participant from the time that the first dose of depatuxizumab mafodotin is administered until 49 days have elapsed following discontinuation of study drug. TEAEs were collected whether elicited or spontaneously reported by the participant.

Standard Steroids

Standard Steroids + Vasoconstrictor + Cold Compress

Enhanced Steroids + Vasoconstrictor + Cold Compress

Total

Age, Continuous

Sex: Female, Male

White

Black or African American

Asian

Race/Ethnicity, Customized

Safety population: All randomized participants who received at least 1 dose of depatuxizumab mafodotin

Global Medical Services

Bilateral vision

Vision in worst eye

Safety population: all randomized participants who received at least 1 dose of depatuxizumab mafodotin and had at least 1 post-baseline assessment within 8 weeks after the initial dose for either LogMAR or CEAE

Percentage of Participants Who Required a Change in Ocular Side Effect (OSE) Management

Safety population: all randomized participants who received at least 1 dose of depatuxizumab mafodotin and had available data.

Maximum Change From Baseline on the Logarithm of the Minimum Angle of Resolution (LogMAR) Scale

Safety population: all randomized participants who received at least 1 dose of depatuxizumab mafodotin and had available data

Time to Bandage Contact Lens (BCL) Intervention

Number of Participants With Depatuxizumab Mafodotin Dose Modifications Due to Ocular Side Effects (OSE)

Cumulative Dose of Depatuxizumab Mafodotin Received During Chemoradiation and During Adjuvant Treatment

Week 1: Grade 0

Week 1: Grade 1

Week 3: Grade 0

Week 3: Grade 1

Week 3: Grade 2

Week 5: Grade 0

Week 5: Grade 1

Week 5: Grade 2

Week 5: Grade 3

Week 7: Grade 0

Week 7: Grade 1

Week 7: Grade 2

Week 7: Grade 3

Week 9: Grade 0

Week 9: Grade 1

Week 9: Grade 2

Week 9: Grade 3

Week 11: Grade 0

Week 11: Grade 1

Week 11: Grade 2

Week 11: Grade 3

Week 11: Grade 4

Week 13: Grade 1

Adj Week 1: Grade 0

Adj Week 1: Grade 1

Adj Week 1: Grade 2

Adj Week 1: Grade 3

Adj Week 5: Grade 0

Adj Week 5: Grade 1

Adj Week 5: Grade 2

Adj Week 5: Grade 3

Adj Week 9: Grade 0

Adj Week 9: Grade 1

Adj Week 9: Grade 2

Adj Week 9: Grade 3

Adj Week 13: Grade 0

Adj Week 13: Grade 1

Adj Week 13: Grade 2

Adj Week 13: Grade 3

Adj Week 17: Grade 0

Adj Week 17: Grade 1

Adj Week 17: Grade 2

Adj Week 21: Grade 1

Adj Week 21: Grade 2

Adj Week 25: Grade 1

Adj Week 25: Grade 2

Adj Week 29: Grade 2

Adj Week 29: Grade 4

Treatment-Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit

Within 8 weeks of first dose: Bilateral vision

Within 8 weeks of first dose: Vision in worst eye

Within 8 weeks of first adjuvant dose: Bilateral vision

Within 8 weeks of first adjuvant dose: Vision in worst eye

Change From Baseline In Logarithm of the Minimum Angle of Resolution (LogMAR) Scale After Bandage Contact Lens (BCL) Intervention

Data were not collected for this outcome (due to early termination of the study).

Percentage of Participants That Recovered to <3-line Decline From Baseline (≤ +0.3 LogMAR) in Visual Acuity After Bandage Contact Lens (BCL) Intervention

Number of Participants With Depatuxizumab Mafodotin Dose Modifications to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention

Time to Restart Depatuxizumab Mafodotin if Interrupted Due to Ocular Side Effects After Bandage Contact Lens (BCL) Intervention

Treatment Emergent Corneal Epithelial Adverse Event (CEAE) Grade at Each Visit After Bandage Contact Lens (BCL) Intervention

Time to Ocular Side Effect (OSE) Symptom Resolution After Drug Discontinuation (Reversibility)

Time to Re-initiation of Depatuxizumab Mafodotin After Dose Interruption

Participants who were randomized to the study but received no doses of depatuxizumab mafodotin or prophylactic eye treatments

Untreated Participants

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
UNITE Study: Understanding New Interventions With GBM ThErapy	NCT03419403	Glioblastoma Mu...	Steroid eye dro... Vasoconstrictor... Cold compress Ophthalmic ster... Depatuxizumab m... Temozolomide Radiation	18 Years -	AbbVie
UNITE Study: Understanding New Interventions With GBM ThErapy	NCT03419403	Glioblastoma Mu...	Steroid eye dro... Vasoconstrictor... Cold compress Ophthalmic ster... Depatuxizumab m... Temozolomide Radiation	18 Years -	AbbVie

Spots Global Cancer Trial Database for ophthalmic steroid ointment