Clinical trial NCT02391480: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2015-03-18
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance status of: 0 - 1 (dose escalation cohorts) or 0 - 2 (expansion cohorts)
4. Participants in the dose escalation cohort must have a serum albumin of ≥ 3.2 g/dL at screening.
5. Adequate bone marrow, renal, and hepatic function.
6. QTc interval \< 480 milliseconds (msec) on the baseline electrocardiogram.

Exclusion Criteria:

1. Participant has untreated brain or meningeal metastases.
2. 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.
3. Participant has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
4. Symptoms of gross hematuria or gross hemoptysis.
5. Exhibits symptomatic or persistent, uncontrolled hypertension (BP \> or = to 140 and/or diastolic pressure of \> or = to 90 mm Hg).
6. History of long QT syndrome.
7. Peripheral neuropathy greater than or equal to grade 2.

Primary outcomes:
measure: Maximum Tolerated Dose of ABBV-075
timeFrame: Minimum first cycle of dosing (28 days) up to one year for dose escalation segment.
measure: Time to Cmax (peak time, Tmax) for ABBV-075
timeFrame: Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
measure: Number of participants with adverse events
timeFrame: Screening, Cycle 1 Day 1, 8 and 15, then Day 1 of each cycle up to approximately 2 years.
measure: Maximum observed plasma concentration (Cmax) of ABBV-075
timeFrame: Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
measure: Area under the curve (AUC)
timeFrame: 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:
measure: Duration of overall response (DOR)
timeFrame: At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
measure: Objective Response Rate (ORR)
timeFrame: At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
measure: Progression Free Survival (PFS)
timeFrame: Screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare /ID# 132963
state: Arizona
city: Duarte
country: United States
facility: City of Hope /ID# 154053
state: California
city: Sacramento
country: United States
facility: UC Davis Comp Cancer Ctr /ID# 154644
state: California
city: New Haven
country: United States
facility: Yale University /ID# 136982
state: Connecticut
city: Chicago
country: United States
facility: University of Chicago /ID# 155453
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ School Medicine /ID# 132946
state: Indiana
city: Durham
country: United States
facility: Duke Univ Med Ctr /ID# 154647
state: North Carolina
city: Dallas
country: United States
facility: Mary Crowley Cancer Research /ID# 154059
state: Texas
city: Houston
country: United States
facility: Univ TX, MD Anderson /ID# 132276
state: Texas
city: Houston
country: United States
facility: UT MD Anderson Cancer Center /ID# 164122
state: Texas
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
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.
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.