Back to resultsA Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Cancer
Primary Purpose
Cancer, Breast Cancer, Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ABBV-075
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Cancer focused on measuring Cancer, Bromodomain Inhibitor
Eligibility Criteria
Inclusion Criteria:
- Participant in the dose escalation cohorts must have histological confirmation of locally advanced or metastatic solid tumor that is either refractory after standard of care therapy for the disease or for which standard of care therapy or does not exist.
- Participants in the expansion cohorts must have histological confirmation of AML, Multiple Myeloma, breast cancer, NSCLC, prostate cancer, SCLC, or NHL that is either refractory after standard of care therapy or for which standard of care therapy does not exist.
- Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance status of: 0 - 1 (dose escalation cohorts) or 0 - 2 (expansion cohorts)
- Participants in the dose escalation cohort must have a serum albumin of ≥ 3.2 g/dL at screening.
- Adequate bone marrow, renal, and hepatic function.
- QTc interval < 480 milliseconds (msec) on the baseline electrocardiogram.
Exclusion Criteria:
- Participant has untreated brain or meningeal metastases.
- Participant has received anti-cancer therapy including chemotherapy, immunotherapy, biologic or any investigational therapy within a period of 21 days prior to Study Day 1.
- Participant has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
- Symptoms of gross hematuria or gross hemoptysis.
- Exhibits symptomatic or persistent, uncontrolled hypertension (BP > or = to 140 and/or diastolic pressure of > or = to 90 mm Hg).
- History of long QT syndrome.
- Peripheral neuropathy greater than or equal to grade 2.
Sites / Locations
- Scottsdale Healthcare /ID# 132963
- City of Hope /ID# 154053
- UC Davis Comp Cancer Ctr /ID# 154644
- Yale University /ID# 136982
- University of Chicago /ID# 155453
- Indiana Univ School Medicine /ID# 132946
- Duke Univ Med Ctr /ID# 154647
- Mary Crowley Cancer Research /ID# 154059
- Univ TX, MD Anderson /ID# 132276
- UT MD Anderson Cancer Center /ID# 164122
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
ABBV-075
ABBV-075 and venetoclax combination
ABBV-075 expansion
Arm Description
Dose escalation cohorts of ABBV-075 monotherapy
Expansion cohorts of ABBV-075 and venetoclax combination therapy
Expansion cohorts of ABBV-075 monotherapy
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose of ABBV-075
Maximum tolerated dose is defined as the highest dose level at which less than 2 of 6 participants experience the same dose limiting toxicity. If more than 2 participants experience a different dose limiting toxicity, the maximum tolerated dose may be further evaluated or determined to be exceeded based on discussions with the investigators and medical monitors.
Time to Cmax (peak time, Tmax) for ABBV-075
Number of participants with adverse events
Maximum observed plasma concentration (Cmax) of ABBV-075
Area under the curve (AUC)
Area under the plasma concentration versus time curve from time 0 (pre-dose) to the time of the last measurable concentration (AUC 0-t).
Secondary Outcome Measures
Duration of overall response (DOR)
DOR is defined as the time from the participant's initial CR or PR to the time of disease progression
Objective Response Rate (ORR)
ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR).
Progression Free Survival (PFS)
PFS is defined as the time from the first dose of ABBV-075 to either disease progression or death, whichever occurs first.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02391480
Brief Title
A Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Cancer
Official Title
A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Advanced Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
April 14, 2015 (Actual)
Primary Completion Date
July 5, 2019 (Actual)
Study Completion Date
July 5, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 1, first-in-human, dose escalation study in participants with advanced solid tumors to determine the pharmacokinetics, maximum tolerated dose and the recommended Phase 2 dose of ABBV-075 at different monotherapy dosing schedules. In addition the study will evaluate the safety. tolerability and the pharmacokinetics of ABBV-075 monotherapy or combination therapy in disease specific expansion cohorts.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Breast Cancer, Non-Small Cell Lung Cancer, Acute Myeloid Leukemia (AML), Multiple Myeloma, Prostate Cancer, Small Cell Lung Cancer, Non-Hodgkins Lymphoma
Keywords
Cancer, Bromodomain Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
128 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABBV-075
Arm Type
Experimental
Arm Description
Dose escalation cohorts of ABBV-075 monotherapy
Arm Title
ABBV-075 and venetoclax combination
Arm Type
Experimental
Arm Description
Expansion cohorts of ABBV-075 and venetoclax combination therapy
Arm Title
ABBV-075 expansion
Arm Type
Experimental
Arm Description
Expansion cohorts of ABBV-075 monotherapy
Intervention Type
Drug
Intervention Name(s)
ABBV-075
Other Intervention Name(s)
Mivebresib
Intervention Description
ABBV-075 Oral tablets
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Venclexta
Intervention Description
Venetoclax tablets, film-coated
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose of ABBV-075
Description
Maximum tolerated dose is defined as the highest dose level at which less than 2 of 6 participants experience the same dose limiting toxicity. If more than 2 participants experience a different dose limiting toxicity, the maximum tolerated dose may be further evaluated or determined to be exceeded based on discussions with the investigators and medical monitors.
Time Frame
Minimum first cycle of dosing (28 days) up to one year for dose escalation segment.
Title
Time to Cmax (peak time, Tmax) for ABBV-075
Time Frame
Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
Title
Number of participants with adverse events
Time Frame
Screening, Cycle 1 Day 1, 8 and 15, then Day 1 of each cycle up to approximately 2 years.
Title
Maximum observed plasma concentration (Cmax) of ABBV-075
Time Frame
Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
Title
Area under the curve (AUC)
Description
Area under the plasma concentration versus time curve from time 0 (pre-dose) to the time of the last measurable concentration (AUC 0-t).
Time Frame
Cycle 1 Day 1 Pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post ABBV-075 dosing, and on Cycle 1 Day 15 at 14, 17, 20 hours post dose.
Secondary Outcome Measure Information:
Title
Duration of overall response (DOR)
Description
DOR is defined as the time from the participant's initial CR or PR to the time of disease progression
Time Frame
At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
Title
Objective Response Rate (ORR)
Description
ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR).
Time Frame
At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from the first dose of ABBV-075 to either disease progression or death, whichever occurs first.
Time Frame
Screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant in the dose escalation cohorts must have histological confirmation of locally advanced or metastatic solid tumor that is either refractory after standard of care therapy for the disease or for which standard of care therapy or does not exist.
Participants in the expansion cohorts must have histological confirmation of AML, Multiple Myeloma, breast cancer, NSCLC, prostate cancer, SCLC, or NHL that is either refractory after standard of care therapy or for which standard of care therapy does not exist.
Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance status of: 0 - 1 (dose escalation cohorts) or 0 - 2 (expansion cohorts)
Participants in the dose escalation cohort must have a serum albumin of ≥ 3.2 g/dL at screening.
Adequate bone marrow, renal, and hepatic function.
QTc interval < 480 milliseconds (msec) on the baseline electrocardiogram.
Exclusion Criteria:
Participant has untreated brain or meningeal metastases.
Participant has received anti-cancer therapy including chemotherapy, immunotherapy, biologic or any investigational therapy within a period of 21 days prior to Study Day 1.
Participant has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
Symptoms of gross hematuria or gross hemoptysis.
Exhibits symptomatic or persistent, uncontrolled hypertension (BP > or = to 140 and/or diastolic pressure of > or = to 90 mm Hg).
History of long QT syndrome.
Peripheral neuropathy greater than or equal to grade 2.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Scottsdale Healthcare /ID# 132963
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258-4566
Country
United States
Facility Name
City of Hope /ID# 154053
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UC Davis Comp Cancer Ctr /ID# 154644
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Yale University /ID# 136982
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
University of Chicago /ID# 155453
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1443
Country
United States
Facility Name
Indiana Univ School Medicine /ID# 132946
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Duke Univ Med Ctr /ID# 154647
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Mary Crowley Cancer Research /ID# 154059
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Univ TX, MD Anderson /ID# 132276
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
UT MD Anderson Cancer Center /ID# 164122
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31420359
Citation
Piha-Paul SA, Sachdev JC, Barve M, LoRusso P, Szmulewitz R, Patel SP, Lara PN Jr, Chen X, Hu B, Freise KJ, Modi D, Sood A, Hutti JE, Wolff J, O'Neil BH. First-in-Human Study of Mivebresib (ABBV-075), an Oral Pan-Inhibitor of Bromodomain and Extra Terminal Proteins, in Patients with Relapsed/Refractory Solid Tumors. Clin Cancer Res. 2019 Nov 1;25(21):6309-6319. doi: 10.1158/1078-0432.CCR-19-0578. Epub 2019 Aug 16.
Results Reference
result
PubMed Identifier
33934351
Citation
Borthakur G, Odenike O, Aldoss I, Rizzieri DA, Prebet T, Chen C, Popovic R, Modi DA, Joshi RH, Wolff JE, Jonas BA. A phase 1 study of the pan-bromodomain and extraterminal inhibitor mivebresib (ABBV-075) alone or in combination with venetoclax in patients with relapsed/refractory acute myeloid leukemia. Cancer. 2021 Aug 15;127(16):2943-2953. doi: 10.1002/cncr.33590. Epub 2021 May 2.
Results Reference
derived
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A Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Cancer
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