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)

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT03234712

Collaborator

(none)

Enrollment

Locations

Arm

42.1

Actual Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors Cancer	Drug: ABBV-321	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Oct 10, 2017

Actual Primary Completion Date :

Apr 14, 2021

Actual Study Completion Date :

Apr 14, 2021

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: ABBV-321 Intravenous infusion Other Names: Serclutamab Talirine

Arm

Intervention/Treatment

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.

Drug: ABBV-321

Intravenous infusion

Other Names:

Serclutamab Talirine

Outcome Measures

Primary Outcome Measures

AUCt for ABBV-321 [Up to 78 days post dose]
Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-321
AUC∞ for ABBV-321 [Up to 78 days post dose]
AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.
Tmax of ABBV-321 [Up to 78 days post dose]
Time to Cmax (Tmax) of ABBV-321
Terminal phase elimination rate constant (β) for ABBV-321 [Up to 78 days post dose]
Terminal phase elimination rate constant (β)
Cmax of ABBV-321 [Up to 78 days post dose]
Maximum observed plasma concentration (Cmax) of ABBV-321
Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for ABBV-321 [Minimum first cycle of dosing (up to 28 days)]
The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Phase
t1/2 for ABBV-321 [Up to 78 days post dose]
Terminal elimination half-life (t1/2)
Dose Escalation Phase: Maximum tolerated dose (MTD) of ABBV-321 [Minimum first cycle of dosing (up to 28 days)]
The MTD of ABBV-321 will be determined during the dose escalation phase of the study.

Secondary Outcome Measures

Progression-Free Survival (PFS) [Up to approximately 5 years]
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.
Duration of Response (DOR) [Up to approximately 5 years]
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.
Disease Control Rate (DCR) [Up to 5 years]
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.
Time to progression (TTP) [Up to approximately 5 years]
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.
Change from Baseline in QTcF [Up to 61 days post dose]
QT interval measurement corrected by Fridericia's formula (QTcF) change from baseline
Overall Survival (OS) [Up to approximately 5 years]
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.
Objective response rate (ORR) [Up to 5 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group /ID# 166132	Springdale	Arkansas	United States	72762
2	The Angeles Clinic and Researc /ID# 166133	Los Angeles	California	United States	90025
3	University of California, Davis Comprehensive Cancer Center /ID# 215012	Sacramento	California	United States	95817
4	Northwestern University Feinberg School of Medicine /ID# 165191	Chicago	Illinois	United States	60611-2927
5	University of Chicago /ID# 166064	Chicago	Illinois	United States	60637
6	Northshore University Health System Dermatology Clinical Trials Unit /ID# 201095	Skokie	Illinois	United States	60077
7	University of Kentucky Markey Cancer Center /ID# 217665	Lexington	Kentucky	United States	40536-7001
8	Dana-Farber Cancer Institute /ID# 212920	Boston	Massachusetts	United States	02215
9	Washington University-School of Medicine /ID# 214955	Saint Louis	Missouri	United States	63110
10	Columbia Univ Medical Center /ID# 167184	New York	New York	United States	10032-3725
11	Stony Brook University Hospital /ID# 216976	Stony Brook	New York	United States	11794-8183
12	Duke University Medical Center /ID# 166135	Durham	North Carolina	United States	27710-3000
13	Lifespan Cancer Institute at Rhode Island Hospital /ID# 168600	Providence	Rhode Island	United States	02903-4923
14	South Texas Accelerated Research Therapeutics /ID# 166134	San Antonio	Texas	United States	78229
15	Northern Cancer Institute /ID# 166138	St Leonards	New South Wales	Australia	2065
16	Monash Health /ID# 217435	Clayton	Victoria	Australia	3168
17	Austin Hospital /ID# 166137	Heidelberg	Victoria	Australia	3084
18	Sheba Medical Center /ID# 166398	Ramat Gan		Israel	5239424