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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02391480
• Other study ID #: M14-546
• Status: Completed
• Phase: Phase 1
• Start date: April 14, 2015
• Est. completion date: July 5, 2019

Study information

• Verified date: July 2019
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. tolerability and the pharmacokinetics of ABBV-075 monotherapy or combination therapy in disease specific expansion cohorts.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: July 5, 2019
• Est. primary completion date: July 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• ABBV-075
ABBV-075 Oral tablets
• Venetoclax
Venetoclax tablets, film-coated

Locations

Country	Name	City	State
United States	University of Chicago /ID# 155453	Chicago	Illinois
United States	Mary Crowley Cancer Research /ID# 154059	Dallas	Texas
United States	City of Hope /ID# 154053	Duarte	California
United States	Duke Univ Med Ctr /ID# 154647	Durham	North Carolina
United States	Univ TX, MD Anderson /ID# 132276	Houston	Texas
United States	UT MD Anderson Cancer Center /ID# 164122	Houston	Texas
United States	Indiana Univ School Medicine /ID# 132946	Indianapolis	Indiana
United States	Yale University /ID# 136982	New Haven	Connecticut
United States	UC Davis Comp Cancer Ctr /ID# 154644	Sacramento	California
United States	Scottsdale Healthcare /ID# 132963	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	Time to Cmax (peak time, Tmax) for ABBV-075		Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
Primary	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.
Primary	Maximum observed plasma concentration (Cmax) of ABBV-075		Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years.
Primary	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	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.
Secondary	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.
Secondary	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.