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)

Advanced Solid Tumors Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03234712
• Other study ID #: M16-438
• Status: Completed
• Phase: Phase 1
• Start date: October 10, 2017
• Est. completion date: April 14, 2021

Study information

• Verified date: May 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: April 14, 2021
• Est. primary completion date: April 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Advanced Solid Tumors Cancer
• Neoplasms

Intervention

Drug:
• ABBV-321
Intravenous infusion

Locations

Country	Name	City	State
Australia	Monash Health /ID# 217435	Clayton	Victoria
Australia	Austin Hospital /ID# 166137	Heidelberg	Victoria
Australia	Northern Cancer Institute /ID# 166138	St Leonards	New South Wales
Israel	Sheba Medical Center /ID# 166398	Ramat Gan
United States	Dana-Farber Cancer Institute /ID# 212920	Boston	Massachusetts
United States	Northwestern University Feinberg School of Medicine /ID# 165191	Chicago	Illinois
United States	University of Chicago /ID# 166064	Chicago	Illinois
United States	Duke University Medical Center /ID# 166135	Durham	North Carolina
United States	University of Kentucky Markey Cancer Center /ID# 217665	Lexington	Kentucky
United States	The Angeles Clinic and Researc /ID# 166133	Los Angeles	California
United States	Columbia Univ Medical Center /ID# 167184	New York	New York
United States	Lifespan Cancer Institute at Rhode Island Hospital /ID# 168600	Providence	Rhode Island
United States	University of California, Davis Comprehensive Cancer Center /ID# 215012	Sacramento	California
United States	Washington University-School of Medicine /ID# 214955	Saint Louis	Missouri
United States	South Texas Accelerated Research Therapeutics /ID# 166134	San Antonio	Texas
United States	Northshore University Health System Dermatology Clinical Trials Unit /ID# 201095	Skokie	Illinois
United States	Highlands Oncology Group /ID# 166132	Springdale	Arkansas
United States	Stony Brook University Hospital /ID# 216976	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 78 days post dose
Primary	AUC8 for ABBV-321	AUC8 is the area under the plasma concentration-time curve from Time 0 to infinite time.	Up to 78 days post dose
Primary	Tmax of ABBV-321	Time to Cmax (Tmax) of ABBV-321	Up to 78 days post dose
Primary	Terminal phase elimination rate constant (ß) for ABBV-321	Terminal phase elimination rate constant (ß)	Up to 78 days post dose
Primary	Cmax of ABBV-321	Maximum observed plasma concentration (Cmax) of ABBV-321	Up to 78 days post dose
Primary	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	Minimum first cycle of dosing (up to 28 days)
Primary	t1/2 for ABBV-321	Terminal elimination half-life (t1/2)	Up to 78 days post dose
Primary	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.	Minimum first cycle of dosing (up to 28 days)
Secondary	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.	Up to approximately 5 years
Secondary	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.	Up to approximately 5 years
Secondary	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.	Up to 5 years
Secondary	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.	Up to approximately 5 years
Secondary	Change from Baseline in QTcF	QT interval measurement corrected by Fridericia's formula (QTcF) change from baseline	Up to 61 days post dose
Secondary	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.	Up to approximately 5 years
Secondary	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.	Up to 5 years