Clinical trial NCT03234712: A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR)
Official title: A Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors Cancer
Keywords: Advanced Solid Tumors
Epidermal Growth Factor Receptor (EGFR)
Squamous cell carcinoma of the head and neck (HNSCC)
non-small cell lung cancer (NSCLC)
Glioblastoma (GBM)
Cancer
overexpression of Epidermal Growth Factor Receptor (EGFR)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-07-31
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, Phase 1, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-321 for participants with advanced solid tumors likely to overexpress the epidermal growth factor receptor (EGFR). The study will consist of 2 phases: Dose Escalation Phase and Expansion Phase.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Histologically or cytologically confirmed solid tumor of one of the following types associated with overexpression of Epidermal Growth Factor Receptor (EGFR). (For Expansion Phase: Subjects must have EGFR overexpression demonstrated by central assessment or Sponsor selected test).

Dose Escalation Phase:

* Colorectal cancer (CRC), Glioblastoma (GBM), squamous cell carcinoma of the head and neck (HNSCC), non-small cell lung cancer (NSCLC), bladder, cervical, esophageal, kidney or sarcoma.
* Participants must have disease that has progressed on prior treatment and is not amenable to surgical resection or other approved therapeutic options with curative intent. Participants must not be eligible for, or has refused further therapy that is likely to provide a survival benefit.
* Must have measureable disease as per RECIST Version 1.1 or RANO (for GBM).
* Minimum life expectancy of at least 12 weeks.

Expansion Phase (Solid Tumor Cohort):

* Histologically or cytologically confirmed advanced solid tumor.
* Participants must have disease that has progressed on prior treatment and is not amenable to surgical resection or other approved therapeutic options with curative intent.
* Must have measureable disease as per RECIST Version 1.1.
* Minimum life expectancy of at least 12 weeks.

Expansion Phase (GBM Cohort Only):

* Participant has recurrent primary (de novo) glioblastoma histologically confirmed at any time from initial diagnosis through latest recurrence.
* Participant has recurrent GBM per Response Evaluation in Neuro-Oncology (RANO) requirements.
* Tumor is measurable according to RANO criteria.

Exclusion Criteria:

* Active uncontrolled infection National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Grade greater than or equal to 3).
* New York Heart Association (NYHA) Class III or IV heart failure and/or ejection fraction of \< 40% as measured by echocardiogram at screening.
* Unstable angina pectoris or cardiac ventricular arrhythmia.
* Myocardial infarction or cerebrovascular accident (CVA) within 6 months.
* Documented history of capillary leak syndrome within 6 months of study enrollment.
* Grade 2 or higher peripheral edema, ascites, pleural, or pericardial effusion within 4 weeks of study enrollment or any history of recurrent grade 2 or higher effusions requiring ongoing drainage.
* Active keratitis or current corneal disorder.
* Laser-assisted in situ keratomileusis (LASIK) procedure within the last 1 year or cataract surgery within the last 3 months.
* Major surgery (including opening of the abdomen, chest) within 21 days of the first dose of study drug.
* Uncontrolled metastases from an extracranial solid tumor to the central nervous system (CNS). Participants with brain metastases from an extracranial solid tumor are eligible after definitive therapy provided they are asymptomatic for at least 2 weeks prior to first dose of ABBV-321.
* No history of medical condition resulting in nephrotic range proteinuria.
* Participants must not have been treated in anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal therapy, biologic therapy or investigational anti-cancer therapy within a period of 21 days or herbal anticancer therapy within 7 days prior to the first dose of study drug.
* For approved targeted small molecules, a washout period of 5 half-lives is adequate (no washout period required for subjects currently on erlotinib)
* Participant must not have been in more than three lines of systemic cytotoxic therapy (excluding adjuvant and neoadjuvant therapy)

Primary outcomes:
measure: AUCt for ABBV-321
timeFrame: Up to 78 days post dose
measure: AUC∞ for ABBV-321
timeFrame: Up to 78 days post dose
measure: Tmax of ABBV-321
timeFrame: Up to 78 days post dose
measure: Terminal phase elimination rate constant (β) for ABBV-321
timeFrame: Up to 78 days post dose
measure: Cmax of ABBV-321
timeFrame: Up to 78 days post dose
measure: Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for ABBV-321
timeFrame: Minimum first cycle of dosing (up to 28 days)
measure: t1/2 for ABBV-321
timeFrame: Up to 78 days post dose
measure: Dose Escalation Phase: Maximum tolerated dose (MTD) of ABBV-321
timeFrame: Minimum first cycle of dosing (up to 28 days)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 5 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 5 years
measure: Time to progression (TTP)
timeFrame: Up to approximately 5 years
measure: Change from Baseline in QTcF
timeFrame: Up to 61 days post dose
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years
measure: Objective response rate (ORR)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group /ID# 166132
state: Arkansas
city: Los Angeles
country: United States
facility: The Angeles Clinic and Researc /ID# 166133
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center /ID# 215012
state: California
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 165191
state: Illinois
city: Chicago
country: United States
facility: University of Chicago /ID# 166064
state: Illinois
city: Skokie
country: United States
facility: Northshore University Health System Dermatology Clinical Trials Unit /ID# 201095
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Markey Cancer Center /ID# 217665
state: Kentucky
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 212920
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 214955
state: Missouri
city: New York
country: United States
facility: Columbia Univ Medical Center /ID# 167184
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital /ID# 216976
state: New York
city: Durham
country: United States
facility: Duke University Medical Center /ID# 166135
state: North Carolina
city: Providence
country: United States
facility: Lifespan Cancer Institute at Rhode Island Hospital /ID# 168600
state: Rhode Island
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics /ID# 166134
state: Texas
city: St Leonards
country: Australia
facility: Northern Cancer Institute /ID# 166138
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health /ID# 217435
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital /ID# 166137
state: Victoria
city: Ramat Gan
country: Israel
facility: Sheba Medical Center /ID# 166398
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: