A Phase III Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel with or without the PARP Inhibitor Veliparib (ABT-888) in Her-2 Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer

Breast cancer (BC) is diagnosed in over 1.3 million women worldwide each year
and accounts for over 500,000 deaths, making it the leading cause of
cancer-related death in women. Although the number of agents approved for the
treatment of advanced breast cancer continues to increase, overall survival has
changed relatively little and median survival remains unchanged, in the range
of 2 to 3 years from initial diagnosis of metastatic disease.

The therapeutic potential of PARP inhibitors was suggested by two clinical
trials evaluating PARP inhibition in breast cancer and one clinical trial in
ovarian cancer. Therapeutic potential in breast cancer has also been observed
with veliparib in combination with carboplatin + paclitaxel.

This is the first randomized, Phase 3 study of veliparib in HER2-negative
metastatic or locally advanced unresectable breast cancer in patients with
clinically significant (suspected deleterious or deleterious) germline mutation
of BRCA1 or BRCA2.

The primary endpoint is to assess the progression-free survival (PFS) of
veliparib in combination with carboplatin (C) and paclitaxel (P) compared to
placebo with C/P in subjects with a BRCA1 and/or BRCA2 Mutation and
HER2-Negative Metastatic or Locally Advanced Unresectable Breast Cancer.

The secondary objectives of the study are to assess overall survival (OS),
clinical benefit rate (CBR), objective response rate (ORR), PFS2 and duration
of overall response (DOR) in subjects treated with veliparib in combination
with C/P versus subjects treated with placebo with C/P. The tertiary objectives
are to assess change in ECOG performance status, change in Quality of Life
(QoL).

This is a Phase 3 randomized, double-blind, multinational, multicenter study.
Subject randomization will be stratified by estrogen receptor (ER) and/or
progesterone receptor (PgR) positive versus ER/PgR negative, prior platinum
therapy (yes versus no), and CNS metastases (yes versus no). Subjects will be
randomized in a 2:1 ratio to one of the two treatment arms.

This study will be conducted in approximately 200 research sites and
approximately 500 subjects will be enrolled.

The Screening procedures will be performed within 28 days prior to the first
dose of study drug (C1 D-2). Subjects in the veliparib/placebo + carboplatin +
paclitaxel treatment arms, have study visits conducted at Day -2, Day 1, Day 8,
and Day 15 of Cycle 1 and Day 1, Day 8 and Day 15
of every cycle thereafter (cycle is 21 days). Subject moving to the crossover
treatment arm, have study visits conducted at Day 1 and Day 15 of Cycle 1 and
Day 1 of every cycle thereafter.

Subjects will continue dosing until they meet the defined discontinuation
criteria. When a subject meets the criteria for study discontinuation, a Final
Visit will be conducted. All subjects will have one Follow-up Visit
approximately 30 days after the last dose of study medication.
Survival information will be collected at two-monthly intervals, beginning on
the date the subject is registered off study and until the endpoint of death,
until the subject has become lost to follow-up or until study termination by
AbbVie.

The burden for the subject consist of extra visits to the site, three times an
ECG, additional blood draws besides the standard safety labs. Next to this the
subject will complete at a maximum 4 questionnaires per visit. Progression of
disease will be measured every nine weeks.

The duration of the study will be different for each subject.. Subjects will
continue the treatment until progression of disease criteria are met or the
subject does not tolerate the treatment.

Based on research the most frequent adverse events are for veliparib in
combination with carboplatin and paclitaxel (> 10%): hair loss, joint pains and
shortness of breath or difficulty breathing.

Based on research the most frequent adverse events are for veliparib alone (>
10%): Feeling sick to your stomach, feeling tired, decreased red blood cells or
hemoglobin (the part of blood that carries oxygen to your body), vomiting,
decreased white blood cells; decreased lymphocytes and decreased neutrophils
(blood cells that help fight infections), diarrhea, decreased platelets (blood
cells which help clot blood and prevent bleeding), decreased appetite,
headache, constipation, stomach pain, difficulty falling asleep and/or staying
asleep, feeling dizzy, change in the sense of taste and dehydration.