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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03234712




Registration number
NCT03234712
Ethics application status
Date submitted
27/07/2017
Date registered
31/07/2017
Date last updated
9/06/2020

Titles & IDs
Public title
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)
Scientific 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)
Secondary ID [1] 0 0
M16-438
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABBV-321

Experimental: ABBV-321 - ABBV-321 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined.


Treatment: Drugs: ABBV-321
Intravenous infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
AUCt for ABBV-321 - Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-321
Timepoint [1] 0 0
Up to 78 days post dose
Primary outcome [2] 0 0
AUC8 for ABBV-321 - AUC8 is the area under the plasma concentration-time curve from Time 0 to infinite time.
Timepoint [2] 0 0
Up to 78 days post dose
Primary outcome [3] 0 0
Tmax of ABBV-321 - Time to Cmax (Tmax) of ABBV-321
Timepoint [3] 0 0
Up to 78 days post dose
Primary outcome [4] 0 0
Terminal phase elimination rate constant (ß) for ABBV-321 - Terminal phase elimination rate constant (ß)
Timepoint [4] 0 0
Up to 78 days post dose
Primary outcome [5] 0 0
Cmax of ABBV-321 - Maximum observed plasma concentration (Cmax) of ABBV-321
Timepoint [5] 0 0
Up to 78 days post dose
Primary outcome [6] 0 0
Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for ABBV-321 - The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Phase
Timepoint [6] 0 0
Minimum first cycle of dosing (up to 28 days)
Primary outcome [7] 0 0
t1/2 for ABBV-321 - Terminal elimination half-life (t1/2)
Timepoint [7] 0 0
Up to 78 days post dose
Primary outcome [8] 0 0
Dose Escalation Phase: Maximum tolerated dose (MTD) of ABBV-321 - The MTD of ABBV-321 will be determined during the dose escalation phase of the study.
Timepoint [8] 0 0
Minimum first cycle of dosing (up to 28 days)
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) - PFS is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first.
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [2] 0 0
Duration of Response (DOR) - DOR for a given participant is defined as the number of days from the day CR or PR (whichever is recorded first) occurred to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first.
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [3] 0 0
Disease Control Rate (DCR) - DCR is defined as the proportion of participants with objective evidence of complete response (CR), partial response (PR) or stable disease (SD); a participants best overall response assignment of SD must be maintained for at least 6 weeks since the first dose date of study drug.
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Time to progression (TTP) - TTP is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST version 1.1 or RANO criteria.
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
Change from Baseline in QTcF - QT interval measurement corrected by Fridericia's formula (QTcF) change from baseline
Timepoint [5] 0 0
Up to 61 days post dose
Secondary outcome [6] 0 0
Overall Survival (OS) - OS is defined as number of days from the date of the first dose to the date of death for all dosed participants. For participants who are not deceased, the data will be censored at the last known date to be alive.
Timepoint [6] 0 0
Up to approximately 5 years
Secondary outcome [7] 0 0
Objective response rate (ORR) - ORR is defined as the proportion of participants with a response of partial response (PR) or better; Response Assessment in Neuro-Oncology (RANO) criteria will be used for glioblastoma (GBM) participants, and Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria will be used for all other participants.
Timepoint [7] 0 0
Up to 5 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital /ID# 217436 - Blacktown
Recruitment hospital [2] 0 0
Royal North Shore Hospital /ID# 217861 - Saint Leonards
Recruitment hospital [3] 0 0
Northern Cancer Institute /ID# 166138 - St Leonards
Recruitment hospital [4] 0 0
Monash Health /ID# 217435 - Clayton
Recruitment hospital [5] 0 0
Austin Hospital /ID# 166137 - Heidelberg
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Rhode Island
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Wisconsin
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Gyeonggido
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul Teugbyeolsi
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03234712
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
847.283.8955
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03234712