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

Phase 1

Completed

• Conditions: Acute Myeloid Leukemia (AML); Multiple Myeloma; Non-Hodgkins Lymphoma; Cancer; Non-Small Cell Lung Cancer; Prostate Cancer; Small Cell Lung Cancer; Breast Cancer
• Interventions: Drug: ABBV-075; Drug: Venetoclax

• Registration Number: NCT02391480
• Lead Sponsor: AbbVie

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-03-12
• Study First Submitted QC: 2015-03-12
• Study First Posted: 2015-03-18
• Study Start: 2015-04-14
• Status Verified: 2019-07
• Primary Completion: 2019-07-05
• Study Completion: 2019-07-05
• Last Update Submitted: 2019-11-27
• Last Update Posted: 2019-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 128

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ABBV-075	ABBV-075	Dose escalation cohorts of ABBV-075 monotherapy
ABBV-075 and venetoclax combination	ABBV-075	Expansion cohorts of ABBV-075 and venetoclax combination therapy
ABBV-075 expansion	ABBV-075	Expansion cohorts of ABBV-075 monotherapy
ABBV-075 and venetoclax combination	Venetoclax	Expansion cohorts of ABBV-075 and venetoclax combination therapy

Primary Outcome Measures

Name	Time	Method
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.
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).

Secondary Outcome Measures

Name	Time	Method
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
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.

Trial Locations

Locations (10)

City of Hope /ID# 154053; 🇺🇸 Duarte, California, United States

UC Davis Comp Cancer Ctr /ID# 154644; 🇺🇸 Sacramento, California, United States

Indiana Univ School Medicine /ID# 132946; 🇺🇸 Indianapolis, Indiana, United States

University of Chicago /ID# 155453; 🇺🇸 Chicago, Illinois, United States

Duke Univ Med Ctr /ID# 154647; 🇺🇸 Durham, North Carolina, United States

Mary Crowley Cancer Research /ID# 154059; 🇺🇸 Dallas, Texas, United States

Univ TX, MD Anderson /ID# 132276; 🇺🇸 Houston, Texas, United States

UT MD Anderson Cancer Center /ID# 164122; 🇺🇸 Houston, Texas, United States

Yale University /ID# 136982; 🇺🇸 New Haven, Connecticut, United States

Scottsdale Healthcare /ID# 132963; 🇺🇸 Scottsdale, Arizona, United States