A Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABBV-075 in Subjects With Advanced Cancer

Conditions
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Cancer, Breast Cancer, Non-Small Cell Lung Cancer, Acute Myeloid Leukemia (AML), Multiple Myeloma, Prostate Cancer, Small Cell Lung Cancer, Non-Hodgkins Lymphoma

Intervention / Treatment
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* Drug: ABBV-075
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABBV-075<br>Dose escalation cohorts of ABBV-075 monotherapy | Drug: ABBV-075<br>* ABBV-075 Oral tablets<br>* Other names: Mivebresib;|
| Experimental: ABBV-075 and venetoclax combination<br>Expansion cohorts of ABBV-075 and venetoclax combination therapy | Drug: ABBV-075<br>* ABBV-075 Oral tablets<br>* Other names: Mivebresib;Drug: Venetoclax<br>* Venetoclax tablets, film-coated<br>* Other names: Venclexta;|
| Experimental: ABBV-075 expansion<br>Expansion cohorts of ABBV-075 monotherapy | Drug: ABBV-075<br>* ABBV-075 Oral tablets<br>* Other names: Mivebresib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Minimum first cycle of dosing (28 days) up to one year for dose escalation segment. | 
| Time to Cmax (peak time, Tmax) for 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. | 
| Maximum observed plasma concentration (Cmax) of ABBV-075 |  | 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). | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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). | 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. | Screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Bromodomain Inhibitor