Acute Myeloid Leukemia (AML), Breast Cancer, Cancer, Multiple Myeloma, Non-Hodgkins Lymphoma, Non-Small Cell Lung Cancer, Prostate Cancer, Small Cell Lung Cancer
Conditions
Keywords
Cancer, Bromodomain Inhibitor
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.
Interventions
DRUGABBV-075
ABBV-075 Oral tablets
DRUGVenetoclax
Venetoclax tablets, film-coated
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve (AUC) | 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). |
| Maximum Tolerated Dose of ABBV-075 | 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 | Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years. | — |
| Maximum observed plasma concentration (Cmax) of ABBV-075 | Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years. | — |
| Number of participants with adverse events | Screening, Cycle 1 Day 1, 8 and 15, then Day 1 of each cycle up to approximately 2 years. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years. | ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR). |
| Progression Free Survival (PFS) | Screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years. | PFS is defined as the time from the first dose of ABBV-075 to either disease progression or death, whichever occurs first. |
| Duration of overall response (DOR) | At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years. | DOR is defined as the time from the participant's initial CR or PR to the time of disease progression |
Countries
United States
Outcome results
None listed