CancerPhase 1NCT02391480
A Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Cancer
A Phase 1 study testing ABBV-075 and Venetoclax in people with Cancer and Breast Cancer, run by AbbVie at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Breast Cancer, Non-Small Cell Lung Cancer
- What is being tested?
- ABBV-075 and Venetoclax
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 128 participants
- Where
- 10 sitesUnited States
- Study dates
- 14 Apr 2015to 5 Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of Chicago /ID# 155453
Chicago, Illinois, 60637-1443
Mary Crowley Cancer Research /ID# 154059
Dallas, Texas, 75230
City of Hope /ID# 154053
Duarte, California, 91010
Duke Univ Med Ctr /ID# 154647
Durham, North Carolina, 27705
Univ TX, MD Anderson /ID# 132276
Houston, Texas, 77030
UT MD Anderson Cancer Center /ID# 164122
Houston, Texas, 77030
Indiana Univ School Medicine /ID# 132946
Indianapolis, Indiana, 46202
Yale University /ID# 136982
New Haven, Connecticut, 06510
UC Davis Comp Cancer Ctr /ID# 154644
Sacramento, California, 95817
Scottsdale Healthcare /ID# 132963
Scottsdale, Arizona, 85258-4566
About this study
Official title: A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Advanced Cancer
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.
- Conditions
- Cancer, Breast Cancer, Non-Small Cell Lung Cancer, Acute Myeloid Leukemia (AML), Multiple Myeloma, Prostate Cancer
- Being tested
- ABBV-075, Venetoclax
- Keywords
- Cancer, Bromodomain Inhibitor
- Medical subject headings
- Neoplasms, Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Leukemia, Myeloid, Acute, Multiple Myeloma, Prostatic Neoplasms, Small Cell Lung Carcinoma, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABBV-075Drug
Also called Mivebresib
ABBV-075 Oral tablets
VenetoclaxDrug
Also called Venclexta
Venetoclax tablets, film-coated
| Study group | Role | What they receive |
|---|---|---|
| ABBV-075 | Experimental | Dose escalation cohorts of ABBV-075 monotherapy Receives: Drug: ABBV-075 |
| ABBV-075 and venetoclax combination | Experimental | Expansion cohorts of ABBV-075 and venetoclax combination therapy Receives: Drug: ABBV-075; Drug: Venetoclax |
| ABBV-075 expansion | Experimental | Expansion cohorts of ABBV-075 monotherapy Receives: Drug: ABBV-075 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Minimum first cycle of dosing (28 days) up to one year for dose escalation segment.
Time to Cmax (peak time, Tmax) for ABBV-075
Measured: Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
Number of participants with adverse events
Measured: Screening, Cycle 1 Day 1, 8 and 15, then Day 1 of each cycle up to approximately 2 years.
Maximum observed plasma concentration (Cmax) of ABBV-075
Measured: Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
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).
Measured: 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 outcomes (3)
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
Measured: At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
Objective Response Rate (ORR)
ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR).
Measured: At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
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.
Measured: Screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2015 (estimated)
- Study start14 Apr 2015
- Primary completion5 Jul 2019
- Study completion5 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02391480
- Sponsor's protocol ID
- M14-546
- Status last verified
- Jul 2019
- First submitted
- 12 Mar 2015
- Last updated
- 29 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31420359Borthakur 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.
PubMed 33934351
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Advanced Cancer
- ClinicalTrials.gov ID
- NCT02391480
- Acronym / sponsor ID
- M14-546
- Conditions
- Cancer, Breast Cancer, Non-Small Cell Lung Cancer, Acute Myeloid Leukemia (AML), Multiple Myeloma, Prostate Cancer
- Keywords
- Cancer, Bromodomain Inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 14 Apr 2015 (actual)
- Primary completion
- 5 Jul 2019 (actual)
- Study completion
- 5 Jul 2019 (actual)
- First posted
- 18 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ABBV-075 | Experimental | Drug: ABBV-075Dose escalation cohorts of ABBV-075 monotherapy |
| ABBV-075 and venetoclax combination | Experimental | Drug: ABBV-075, Drug: VenetoclaxExpansion cohorts of ABBV-075 and venetoclax combination therapy |
| ABBV-075 expansion | Experimental | Drug: ABBV-075Expansion cohorts of ABBV-075 monotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABBV-075Also: MivebresibABBV-075 Oral tablets | Drug | ABBV-075, ABBV-075 and venetoclax combination, ABBV-075 expansion |
| VenetoclaxAlso: VenclextaVenetoclax tablets, film-coated | Drug | ABBV-075 and venetoclax combination |
Primary outcome
Maximum Tolerated Dose of ABBV-075
Time frame: Minimum first cycle of dosing (28 days) up to one year for dose escalation segment.
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
Time frame: Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
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.
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.
Area under the curve (AUC)
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.
Area under the plasma concentration versus time curve from time 0 (pre-dose) to the time of the last measurable concentration (AUC 0-t).
3 secondary outcomes
Duration of overall response (DOR)
Time frame: At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
Objective Response Rate (ORR)
Time frame: At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
Progression Free Survival (PFS)
Time frame: Screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2019.
- Results publication: PubMed 31420359Piha-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.
- Derived from this study: PubMed 33934351Borthakur 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
AbbVie Inc. study director
AbbVie
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ABBV-075 and Venetoclax in people with Cancer and Breast Cancer, run by AbbVie at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose of ABBV-075 (time frame: Minimum first cycle of dosing (28 days) up to one year for dose escalation segment.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02391480, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019.