NCT02391480

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
128

participants targeted

Target at P75+ for phase_1 cancer

Timeline
Completed

Started Apr 2015

Typical duration for phase_1 cancer

Geographic Reach
1 country

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 12, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 18, 2015

Completed
27 days until next milestone

Study Start

First participant enrolled

April 14, 2015

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 5, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 5, 2019

Completed
Last Updated

November 29, 2019

Status Verified

July 1, 2019

Enrollment Period

4.2 years

First QC Date

March 12, 2015

Last Update Submit

November 27, 2019

Conditions

Keywords

CancerBromodomain Inhibitor

Outcome Measures

Primary Outcomes (5)

  • 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 Outcomes (3)

  • 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.

  • Objective Response Rate (ORR)

    At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.

  • Progression Free Survival (PFS)

    Screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years.

Study Arms (3)

ABBV-075

EXPERIMENTAL

Dose escalation cohorts of ABBV-075 monotherapy

Drug: ABBV-075

ABBV-075 and venetoclax combination

EXPERIMENTAL

Expansion cohorts of ABBV-075 and venetoclax combination therapy

Drug: ABBV-075Drug: Venetoclax

ABBV-075 expansion

EXPERIMENTAL

Expansion cohorts of ABBV-075 monotherapy

Drug: ABBV-075

Interventions

ABBV-075 Oral tablets

Also known as: Mivebresib
ABBV-075ABBV-075 and venetoclax combinationABBV-075 expansion

Venetoclax tablets, film-coated

Also known as: Venclexta
ABBV-075 and venetoclax combination

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Scottsdale Healthcare /ID# 132963

Scottsdale, Arizona, 85258-4566, United States

Location

City of Hope /ID# 154053

Duarte, California, 91010, United States

Location

UC Davis Comp Cancer Ctr /ID# 154644

Sacramento, California, 95817, United States

Location

Yale University /ID# 136982

New Haven, Connecticut, 06510, United States

Location

University of Chicago /ID# 155453

Chicago, Illinois, 60637-1443, United States

Location

Indiana Univ School Medicine /ID# 132946

Indianapolis, Indiana, 46202, United States

Location

Duke Univ Med Ctr /ID# 154647

Durham, North Carolina, 27705, United States

Location

Mary Crowley Cancer Research /ID# 154059

Dallas, Texas, 75230, United States

Location

Univ TX, MD Anderson /ID# 132276

Houston, Texas, 77030, United States

Location

UT MD Anderson Cancer Center /ID# 164122

Houston, Texas, 77030, United States

Location

Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Conditions

NeoplasmsBreast NeoplasmsCarcinoma, Non-Small-Cell LungLeukemia, Myeloid, AcuteMultiple MyelomaProstatic NeoplasmsSmall Cell Lung CarcinomaLymphoma, Non-Hodgkin

Interventions

mivebresibvenetoclax

Condition Hierarchy (Ancestors)

Neoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeHematologic DiseasesHemic and Lymphatic DiseasesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesGenital Neoplasms, MaleUrogenital NeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital DiseasesLymphomaLymphatic Diseases

Study Officials

  • AbbVie Inc.

    AbbVie

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 12, 2015

First Posted

March 18, 2015

Study Start

April 14, 2015

Primary Completion

July 5, 2019

Study Completion

July 5, 2019

Last Updated

November 29, 2019

Record last verified: 2019-07

Data Sharing

IPD Sharing
Will not share

Locations