Conditions: Non-small Cell Lung Cancer Stage III
Keywords: veliparib PARP inhibitor ABT-888 first line previously untreated stage III non-small cell lung cancer radiotherapy paclitaxel carboplatin
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 48
Healthy volunteers: no

Brief summary:
This study seeks to establish

* the recommended Phase 2 dose (RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based chemoradiotherapy (CRT) and consolidation with paclitaxel/carboplatin-based chemotherapy (Phase 1 portion), and
* to assess whether the addition of oral veliparib versus placebo to paclitaxel/carboplatin-based chemoradiotherapy with paclitaxel/carboplatin consolidation will improve progression-free survival (PFS) in adults with Stage III non-small cell lung cancer (Phase 2 portion).

A strategy decision was made not to proceed to Phase 2 portion of this study due to change in standard of care.

Detailed description:
This was to be a 2-phase study consisting of

1. A Phase 1, dose escalation study of veliparib to determine a RPTD for combination with concurrent paclitaxel/carboplatin-based CRT and paclitaxel/carboplatin-based consolidation chemotherapy; followed by
2. A Phase 2, randomized, double-blinded study to determine whether veliparib improved outcome relative to placebo when added to paclitaxel/carboplatin based CRT followed by consolidation paclitaxel/carboplatin in adults with previously untreated Stage III NSCLC.

In the dose escalation phase (Phase 1) of the study participants will be assigned to ascending doses of veliparib in combination with carboplatin, paclitaxel, and thoracic radiotherapy for 7 weeks following a traditional "3 + 3" design. The first cohort of at least 3 - 6 participants will receive veliparib 60 mg twice a day (BID) throughout CRT. Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new dosing cohort is opened or until the RPTD is identified. Participants will also receive a consolidation dose of veliparib of 120 mg BID + carboplatin and paclitaxel for up to two 21-day cycles. Once the concurrent CRT RPTD is identified, an additional cohort will be enrolled to explore the tolerability of a consolidation dose of veliparib at 240 mg BID + carboplatin + paclitaxel for up to two 21-day cycles.

Following the dose escalation portion of the study, the RPTD will be determined by the sponsor and the Phase 2 portion of the study will begin with patient randomization in a 1:1:1 ratio to concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/veliparib, concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/placebo, or concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo. Randomization will be stratified by tumor volume (≤ 90 versus \> 90 cm³) and smoking history (current smoker versus former smoker versus never smoked).

Phase 2 was not carried out since during the study there was a change in standard of care for patients with newly diagnosed, unresectable Stage III NSCLC.

Arms:
arm 1: Participants in Phase 1 will be sequentially assigned to ascending dose levels of 60 mg, 80 mg, 120 mg, 200 mg, and 240 mg of twice daily (BID) veliparib in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks.

After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. arm 2: Participants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks.

After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. arm 3: Participants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks.

After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. arm 4: Participants will receive placebo to veliparib with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks.

After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.

Interventions: intervention 1: Paclitaxel intervention 2: Placebo for Veliparib intervention 3: Carboplatin intervention 4: Veliparib intervention 5: Radiotherapy
Intervention descriptions: intervention 1: Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation) intervention 2: Capsule for oral administration intervention 3: Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation) intervention 4: Capsule for oral administration intervention 5: Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks

Protocol document:
Prot_SAP_000.pdf: 
Veliparib
M14-360 Protocol Amendment 4
1
1.0
Title Page
Clinical Study Protocol M14-360
A Phase 1 Dose Escalation and Phase 2 Randomized, 
Placebo-Controlled Study of the Efficacy and 
Tolerability of Veliparib in Combination with 
Paclitaxel/Carboplatin-Based Chemoradiotherapy 
Followed by Veliparib and Paclitaxel/Carboplatin 
Consolidation in Subjects with Stage III Non-Small 
Cell Lung Cancer (NSCLC)
Incorporating Amendments 1, 2, 3 and 4
AbbVie Investigational
  Product:
Veliparib/ABT-888
Date:
15 August 2017
Development Phase:
1/2
Study Design:
A Phase 1 Dose Escalation and Phase 2 Randomized, 
Placebo-Controlled Study of the Efficacy and Tolerability of 
Veliparib in Combination with Paclitaxel/Carboplatin Based 
Chemoradiotherapy Followed by Veliparib and 
Paclitaxel/Carboplatin Consolidation in Subjects with Stage III 
Non-Small Cell Lung Cancer (NSCLC)
Investigator(s):
Multicenter Trial:  Investigator information is on file at AbbVie
Sponsor:
AbbVie
Sponsor/Emergency 
  Contact:
AbbVie
1 North Waukegan Road
North Chicago, IL 60064
Phone:
Fax:
*The specific contact details of the AbbVie legal/regulatory entity (person) within the relevant country are provided
within the clinical trial agreement with the Investigator/Institution and in the Clinical Trial Application with the 
Competent Authority.
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other applicable regulatory 
requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
NCT02412371


Veliparib
M14-360 Protocol Amendment 4
2
1.1
Protocol Amendment:  Summary of Changes
Previous Protocol Versions 
Protocol 
Date
Original
27 August 2014
Amendment 1
24 November 2014
Amendment 2
20 January 2016
Amendment 3
29 September 2016
The primary purpose of this amendment is to update the dose escalation plan, to add 
pulmonary function testing (PFT) at 12 months post start chemoradiotherapy (CRT), and 
to include the following changes: 
●
Update information in Section 1.0, Title Page.
Rationale:  Sponsor/Emergency Contact details updated.
●
Update information in Section 1.2, Synopsis.
Rationale:  Change is to correct previous error so Reference Therapy was 
updated.
●
Update Phase 1 doses in Table 1, Dose Escalation in the consolidation 
chemotherapy, and throughout protocol.
Rationale:  Change is to allow for additional dose level of 240 mg BID to be 
evaluated in Phase 1 consolidation chemotherapy.
●
Update planned number of Phase 1 subjects throughout protocol.
Rationale:  Due to additional dose level and over-enrollment in previous 
cohorts, the previous estimate of approximately 30 subjects to be enrolled in 
Phase 1 is no longer accurate. 
●
Update information in Section 1.3, List of Abbreviations and Definition of 
Terms.
Rationale:  Change is to add the "DLCO" abbreviation.
●
Update information in Section 5.2, Selection of Study Population, and 
throughout protocol.


Veliparib
M14-360 Protocol Amendment 4
3
Rationale:  Change is to update the DLT period definition for the additional 
cohort and to describe the roll over process.
●
Update information in Section 5.2, Selection of Study Population, and 
throughout protocol.
Rationale: Inclusion criteria changed for mandating the consent for the 
archived tissue sample collection.
●
Update information in Section 5.3.1, Efficacy and Safety Measurements 
Assessed and Flow Chart.
Rationale:  12 month post start CRT visit added to include PFT assessment to 
follow up on late fibrosis events.  PFT at 12 months post start of CRT added to 
the Post Treatment visit to follow up on late fibrosis events. 
●
Update information in Section 5.3.1, Efficacy and Safety Measurements 
Assessed and Flow Chart.
Rationale:  Archived tissue sample collection changed from optional to 
mandatory.
●
Update information in Section 6.6.3, Reporting Serious Adverse Events.
Rationale:  Primary Study Designated Physician details updated.
●
Update information in Section 7.0, Protocol Deviations.
Rationale:  Medical Monitor details updated; Clinical Monitor details 
removed.
●
Update information in Appendix B, List of Protocol Signatories.
Rationale:  Medical Director details updated.
●
Other changes to the protocol are minor administrative changes throughout the 
document for clarification and for typographical and grammatical error 
corrections.
An itemized list of all changes made to the protocol under this amendment is found in 
Appendix F.


Veliparib
M14-360 Protocol Amendment 4
4
1.2
Synopsis
AbbVie Inc.
Protocol Number:  M14-360
Name of Study Drug:  Veliparib/ABT-888
Phase of Development:  1/2
Name of Active Ingredient:  Not Applicable
Date of Protocol Synopsis:  15 August 2017
Protocol Title:  A Phase 1 Dose Escalation and Phase 2 Randomized, Placebo-Controlled Study of the 
Efficacy and Tolerability of Veliparib in Combination with Paclitaxel/Carboplatin-Based 
Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Subjects with 
Stage III Non-Small Cell Lung Cancer (NSCLC)
Objective(s):  
The primary objectives of the study are to establish the recommended Phase 2 dose (RPTD) of veliparib 
in combination with concurrent Paclitaxel/Carboplatin-based chemoradiotherapy and consolidation with 
Paclitaxel/Carboplatin-based chemotherapy (Phase 1 portion) and to assess whether the addition of oral 
veliparib versus placebo to Paclitaxel/Carboplatin-based chemoradiotherapy with Paclitaxel/Carboplatin 
consolidation will improve progression-free survival (PFS) in patients with Stage III non-small cell lung 
cancer (Phase 2 portion).
The secondary objectives of the study are to assess overall survival (OS), objective response rate (ORR), 
duration of overall response (DOR), safety and tolerability of veliparib versus placebo added to standard 
therapy (Phase 2 portion).
The tertiary objectives are to assess Quality of Life (QoL) (Phase 2 portion) and ECOG performance 
status.  In addition, biomarkers including, but not limited to, defects in DNA-repair genes will be 
assessed in correlation with safety and efficacy data.
Investigator(s):  Multicenter
Study Site(s):  Approximately 50 – 75
Study Population:  Subjects with Stage III NSCLC suitable for definitive chemoradiotherapy (CRT) 
who have not received prior therapy for NSCLC
Number of Subjects to be Enrolled:  Approximately 50 in the dose escalation portion and 
approximately 156 in the randomized portion of the study.
Methodology:  
This two-phase study consists of 1) dose-escalation of veliparib to determine an RPTD for combination 
with concurrent paclitaxel/carboplatin-based CRT; and followed by 2) a randomized, double-blinded 
study to determine whether veliparib improves outcome relative to placebo when added to 
Paclitaxel/Carboplatin-based CRT followed by consolidation Paclitaxel/Carboplatin in subjects with 
previously untreated Stage III NSCLC.


Veliparib
M14-360 Protocol Amendment 4
5
Methodology (Continued):
In the dose escalation phase of the study, subjects will receive veliparib in combination with carboplatin 
AUC 2+ paclitaxel 45 mg/m2 + thoracic radiotherapy.  Radiation delivery will be over no more than 
9 weeks by 3-dimensional conformal radiotherapy or intensity modulated radiotherapy (IMRT), and the 
total dose will be 60 – 63 Gy.  The first cohort of at least 3 – 6 subjects will receive veliparib 60 mg BID 
throughout CRT.  Based on tolerability, subsequent cohorts will receive doses of veliparib from 40 mg 
BID to 240 mg BID.  As the CRT RPTD dose is explored (Cohorts 1 – 5), the consolidation RPTD of 
veliparib will be 120 mg BID + carboplatin AUC 6 + paclitaxel 200 mg/m2 for up to two 21-day cycles.  
The consolidation dose of veliparib in Cohort 6 will be 240 mg BID + carboplatin AUC 6 + paclitaxel 
200 mg/m2 for up to two 21-day cycles.  
Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new dosing cohort is 
opened or until the recommended Phase 2 dose is identified.  A minimum of 3 subjects will be enrolled in 
each cohort.  Additional eligible subjects may be enrolled at the current dose level at the discretion of the 
Investigators and the AbbVie Medical Monitor.  From each cohort, subjects will be entered into the DLT 
assessment group of the intended cohort size in order of treatment.  For Cohorts 1 – 5, subjects 
considered evaluable for DLTs will be those that receive treatment through 1 cycle of CRT or have AEs 
meeting DLT criteria.  For Cohort 6, subjects considered evaluable for DLTs will be those that receive 
treatment through 1 cycle of consolidation chemotherapy.  If a subject in the DLT assessment group 
becomes unevaluable, the subject will be replaced by the next-treated subject in the cohort.  The DLT 
period for each subject participating in Cohorts 1 – 5 will be from start of veliparib dosing through 
28 days following completion of CRT or until consolidation chemotherapy is initiated.  The DLT period 
for each subject participating in Cohort 6, will be from the start of Cycle 1 of the consolidation 
chemotherapy through the start of the Cycle 2 of the consolidation therapy or treatment discontinuation.  
The DLT period for all subjects at each dose level will end upon initiation of next dose level.
Dose limiting toxicities are the following events that are considered by the investigator group to be 
related to treatment:
1.
Radiation induced Grade 3 or greater cardiac toxicity (e.g., myocarditis, pericarditis, heart failure, 
ventricular dysfunction, myocardial infarction). 
2.
Radiation induced myelopathy/myelitis (does not include L'Hermitte's syndrome).
3.
Radiation-related pneumonitis resulting in delay in radiotherapy, chemotherapy (CRT or
consolidation) or veliparib of more than 3 weeks or early discontinuation of RT (total dose < 50 Gy).
4.
G4 or greater esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment 
interruption of > 7 days despite medical management.
5.
G2 or greater seizure.
6.
Grade 4 or greater neutropenia for > 7 days or neutropenic fever (defined as ANC < 500 and a 
temperature of 38.5°C or above).
7.
Grade 4 or greater thrombocytopenia.
8.
Grade 4 diarrhea or nausea/vomiting despite appropriate antiemetic therapy lasting > 48 hours.
9.
Any other toxicity resulting in delay in radiotherapy, chemotherapy, or veliparib of more than 
14 days or early discontinuation of RT (total dose < 50 Gy).


Veliparib
M14-360 Protocol Amendment 4
6
Methodology (Continued):
10. All other non-hematologic toxicities of Grade 3 or greater, with the following exceptions:
a.
Anorexia
b.
Fatigue
c.
Grade 3 infection
d.
Grade 3 AST/ALT elevations ≤ 7 days
e.
Infusion reactions.  Patients with Grade 3 or worse infusion reactions will be removed from 
study and replaced and will not be considered evaluable for DLT
f.
Grade 3 or 4 lymphopenia
g.
Grade 3 or 4 electrolyte abnormalities that are corrected to Grade 2 or less in less than 48 hours
For Cohort 6, if 3 or fewer subjects were able to take Cycle 2 of consolidation chemotherapy, the reason 
of dose reduction and treatment discontinuation will be reviewed as part of consideration to determine 
MTD/RPTD of veliparib for the consolidation phase.
Following the dose escalation portion of the trial, the RPTD will be determined by the sponsor, and at the 
discretion of the sponsor, the Phase 2 portion of the study will begin with patient randomization in a 
1:1:1 ratio to the treatment arms as follows:
A.
Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/veliparib
B.
Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/placebo
C.
Concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation 
paclitaxel/carboplatin/placebo
Subject randomization will be stratified by tumor volume (≤ 90 versus > 90 cm3) and smoking history 
(current smoker versus former smoker versus never smoked).  Screening procedures, QoL assessment, 
and baseline radiographic tumor assessments will be performed within 28 days prior to randomization.
Concurrent chemoradiotherapy (CRT) will consist of radiotherapy (RT) using either 3D conformal RT or 
IMRT plus paclitaxel, (45 mg/m2 as a 60 minute infusion), immediately followed by carboplatin, 
(AUC 2 mg/mL/min as a 30 minute infusion) weekly beginning on Day 1 of radiotherapy.  Veliparib (or 
placebo), will be administered continuously beginning 3 days prior to RT through one day after RT 
completion.
Consolidation chemotherapy will begin no more than 8 weeks following RT.  Subjects who require 
> 8 weeks to recover from toxicities resulting from CRT should not receive consolidation chemotherapy.  
Consolidation chemotherapy will consist of paclitaxel, (200 mg/m2 as a 3 hour infusion, immediately 
followed by carboplatin, AUC 6 mg/mL/min as a 30 minute infusion) on Day 1 of each 21-day cycle for 
up to 2 cycles.  Veliparib (or Placebo in the Phase 2 portion), 120 mg (Cohorts 1 – 5) or 240 mg 
(Cohort 6) BID, will begin on Day –2 (2 days prior to the start of paclitaxel/carboplatin infusion) and will 
continue through Day 5 of each 21-day cycle.  
Subjects who experience toxicities due to carboplatin, paclitaxel, RT, or veliparib/placebo may require a 
delay in the dosing schedule or a dose modification.


Veliparib
M14-360 Protocol Amendment 4
7
Methodology (Continued):
Radiographic tumor assessments will be conducted at baseline, prior to consolidation chemotherapy, at 
24 weeks after start of treatment, every 8 weeks until one year after beginning therapy, then every 
12 weeks.  Beginning 12 weeks after randomization, progression will be determined based on Response 
Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.  Progression prior to that time will be 
determined by the Investigator.  A QoL assessment as measured by the EORTC QLQ-C15-PAL and the 
companion symptom module EORTC QLQ-LC13 will be performed at Screening, prior to consolidation 
chemotherapy, at 24 weeks after start of treatment, every 8 weeks until one year after beginning therapy 
and at the final visit.
After completion of protocol therapy, subjects will be observed without further therapy until progression.  
The visit at which an investigator identifies disease progression or at which a subject meets other criteria 
for study discontinuation will be considered the final visit.  All subjects with a final visit < 30 days after 
the last dose of drug will have one Follow-Up Visit approximately 30 days after the Final Visit.
If a subject is discontinued from the study with an ongoing adverse event or an unresolved clinically 
significant laboratory result, the site will attempt to provide follow-up until a satisfactory clinical 
resolution of the laboratory results or adverse event is achieved.
To ensure subject safety, an internal data monitoring committee (DMC) will review un-blinded safety 
data when approximately 45 subjects in the Phase 2 portion of the study have completed CRT, reached an 
event of disease progression or death, or discontinued the study.
Diagnosis:  Stage III NSCLC
Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion (Phase 1 and Randomized Phase 2):
!
Subject must be ≥ 18 years of age;
!
Subject must have histologically or cytologically confirmed Stage III NSCLC.  When pleural fluid 
is visible on the CT scan or on a chest x-ray, a thoracentesis is required to confirm that the pleural 
fluid is serous AND cytologically negative.  Effusions that are minimal (i.e., not visible on chest 
x-ray) or that are too small to safely tap are exempted from the requirement for thoracentesis. 
!
Subjects in the randomized portion of the study must have measurable disease per RECIST 
version 1.1 criteria;
!
Subject must consent to provide archived tissue or cytology sample of NSCLC lesion for analysis;
!
Subjects must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) 
< 35%;
!
Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 – 1;


Veliparib
M14-360 Protocol Amendment 4
8
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Inclusion (Continued):
!
Subject must have adequate hematologic, renal, hepatic, and lung function as follows: 
o
Bone marrow:  Absolute Neutrophil count (ANC) ≥ 1,500/μL; Platelets ≥ 100,000/mm3; 
Hemoglobin ≥ 9.0 g/dL (without transfusion);
o
Renal function:  calculated creatinine clearance ≥ 50 mL/min by the Cockcroft-Gault formula;
o
Hepatic function and enzymes:  aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) ≤ 2.5 × the upper limit of normal (ULN) of institution's normal range;
Bilirubin ≤ 1.5 × ULN; subjects with Gilbert's syndrome may have a bilirubin ≥ 1.5 × ULN of 
central laboratory normal range; 
o
Pulmonary function tests (PFTs) including FEV1 within 12 weeks prior to randomization; for 
FEV1, the best value obtained pre- or post-bronchodilator must be ≥ 1.2 liters/second and/or 
≥50% predicted.
!
Female subjects of childbearing potential (i.e., those who are not postmenopausal for at least 1 year 
or surgically sterile by bilateral tubal ligation, bilateral oophorectomy or hysterectomy) and their 
male partner should practice at least one of the methods of birth control listed below for at least 
6 months after treatment with chemotherapy.  Male subjects and their female partners of 
childbearing potential should practice at least one of the methods of birth control listed below for 
at least 6 months after treatment with chemotherapy:
o
Total abstinence from sexual intercourse (if it is the subject's preferred and usual lifestyle; 
beginning a minimum one complete menstrual cycle prior to study drug administration and to 
extend 6 months after treatment);
o
Vasectomized subject or partner(s), vasectomy (males);
o
Intrauterine device (females);
o
Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with 
spermicidal jellies or creams; both males and females);
o
Hormonal contraceptives (oral, parenteral or transdermal) for at least 90 days prior to study 
drug administration (females).  If hormonal contraceptives are used, the subject and her 
partner should also use a single barrier method.
o
Subject must voluntarily sign and date an informed consent, approved by an Independent 
Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of and 
Screening for study-specific procedures.


Veliparib
M14-360 Protocol Amendment 4
9
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Exclusion:  
!
Subject with prior chemotherapy or radiotherapy for current NSCLC; subjects curatively treated 
for past early stage NSCLC greater than 3 years ago may be included;
!
Subject with prior exposure to PARP inhibitors;
!
Subjects with known hypersensitivity to carboplatin, paclitaxel, or formulations containing 
polyethoxylated castor oil (Cremophor);
!
Subject with prior mediastinal or thoracic radiotherapy.  Prior tangential RT to prior breast 
cancer is acceptable;
!
Subject with major surgery in the 4 weeks prior to randomization (VATS and/or 
mediastinoscopy is not considered major surgery);
!
Subject with a previous or concurrent malignancy except for treated basal cell or squamous cell 
skin cancer, in situ cervical cancer, or other cancer for which the patient received potentially 
curative treatment and has been disease-free for 3 years or is considered cured by the 
investigator if has been disease-free for less than 3 years;
!
Any medical condition, which in the opinion of the study investigator, places the subject at an 
unacceptably high risk for toxicities, or any subject circumstance that prohibits trial participation 
according to local law;
!
Subject is pregnant or lactating;
!
Subject with sensory peripheral neuropathy of ≥ Grade 2 at baseline;
!
Subject is unable to swallow medication;
!
Subjects with prior history of seizure within the prior 12 months.
Investigational Product:
Veliparib (ABT-888) or Placebo
Dose(s):
60 – 240 mg BID (concurrent chemoradiotherapy); 
120 – 240 mg BID (consolidation)
Mode of Administration:
Oral
Reference Therapy:
Carboplatin 
Dose(s):
AUC 2 mg/mL/min (concurrent chemoradiotherapy); 
AUC 6 mg/mL/min (consolidation)
Mode of Administration:
Intravenous
Reference Therapy:
Paclitaxel
Dose(s):
45 mg/m2 (concurrent chemoradiotherapy);
200 mg/m2 (consolidation)
Mode of Administration:
Intravenous
Duration of Treatment:  
Subjects without clinical progression of disease and with tolerable side effects should continue to receive 
treatment until completion of all prescribed cycles (chemoradiotherapy plus 2 cycles of consolidation 
chemotherapy).


Veliparib
M14-360 Protocol Amendment 4
10
Criteria for Evaluation:
Efficacy:
Progression-free survival (PFS) will be derived according to radiographic progression per RECIST 
version 1.1 (beginning with the second scan after completion of CRT) or death.  Radiographic tumor 
assessments for response will be conducted at baseline, prior to consolidation chemotherapy, at 24 weeks 
after start of treatment, every 8 weeks until one year after beginning therapy, then every 12 weeks until 
radiographic progression or death.  Subjects who require additional therapy, withdraw consent, or are lost 
to follow-up prior to radiographic progression will be censored at that time for the analysis of PFS.
Overall survival (OS) will be determined by the Investigator until radiographic progression.  After 
radiographic progression, survival information will be collected via the electronic CRF at 8-week 
intervals (or as requested by sponsor to support data analysis).
Objective response rate (ORR), and duration of overall response (DOR) will be derived per RECIST 
version 1.1.  Radiographic tumor assessments for response will be conducted at baseline, prior to 
consolidation chemotherapy, at 24 weeks after start of treatment, every 8 weeks until one year after 
beginning therapy, then every 12 weeks until radiographic progression or death.  Subjects who require 
additional therapy, withdraw consent, or are lost to follow-up prior to radiographic progression will be 
censored at that time for the analysis of DOR.
ECOG performance status will be determined by the Investigator at each assessment.  A quality of life 
assessment as measured by the EORTC QLQ-C15-PAL and the companion symptom module EORTC 
QLQ-LC13 will be performed at screening, prior to consolidation chemotherapy, at 24 weeks after start 
of treatment, every 8 weeks until one year after beginning therapy and at the final visit.
Pharmacokinetic:
Blood samples for veliparib assay will be collected for the determination of pharmacokinetic parameters 
of veliparib such as apparent oral clearance (CL/F) and volume of distribution (V/F).
Pharmacodynamic:
Research to find biomarkers that may serve as surrogates for clinical endpoints in future veliparib studies 
or that may be predictive of veliparib activity will be conducted.  Serum, plasma, blood and archived 
tissue samples will be collected at designated time points throughout the study.  Study-specific core 
biopsies are requested but are not required.
Safety:
Adverse events, laboratory profiles, physical examinations and vital signs will be assessed throughout the 
study.  Results will be tabulated for each subject and summary statistics will be computed for each 
sampling time and each parameter.


Veliparib
M14-360 Protocol Amendment 4
11
Statistical Methods:
The following efficacy endpoint will be analyzed using data obtained from subjects in Phase 1:
Objective Response Rate (ORR)
The proportion of subjects with objective response as assessed by the investigator using RECIST 
version 1.1 will be calculated for all dosed subjects. 
The following efficacy endpoints will be analyzed using data obtained from subjects in Phase 2:
Progression-Free survival (PFS)
Progression-Free Survival will be defined as the number of days from the date of randomization to the 
date of earliest radiographic disease progression or death.  All radiographic disease progression will be 
included regardless whether the event occurred while the subject was taking study drug or had previously 
discontinued study drug.  If the subject does not experience radiographic disease progression or death, 
then the data will be censored at the date of the last disease assessment.
Overall Survival (OS)
Overall survival will be defined as the number of days from the date of randomization to the date of 
death.  For subjects who did not die, their data will be censored at the date of last study visit or the last 
known date to be alive, whichever is later.
Objective Response Rate (ORR) 
The proportion of subjects with objective response as assessed by the investigator using RECIST 
version 1.1 will be evaluated for randomized subjects. 
Duration of Overall Response (DOR)
Duration of overall response will be defined as the number of days from the date of first response (CR or 
PR) to the earliest documentation of radiographic progressive disease or death due to disease progression.  
If a subject is still responding, then the subject's data will be censored at the date of the subject's last 
available disease assessment.  For subjects who never experience response, the subject's data will not be 
included in the analysis.
Quality of life (QoL) Measures
Changes and/or percent changes from baseline will be summarized using descriptive statistics for each 
scheduled post-baseline visit and for the Final Visit for quality of life measures using the EORTC 
QLQ-C15-PAL and EORTC QLQ-LC13 questionnaires.  The QoL will be used as an exploratory 
endpoint and not tested against pre-specified hypothesis.
Performance Status
Changes and/or percent changes from baseline will be summarized using descriptive statistics for each 
scheduled post-baseline visit and for the Final Visit for ECOG performance status.  Post-baseline 
measurements more than 30 days after the last dose of study drug will not be included.  Subjects that do 
not have a baseline measurement or do not have any post-baseline measurements will not be included.
Efficacy Analysis:
The primary Phase 2 efficacy analysis will test if concurrent paclitaxel/carboplatin/radiotherapy/veliparib 
followed by consolidation paclitaxel/carboplatin/veliparib (Arm A) will improve PFS versus concurrent 
paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo 
(Arm C).


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Statistical Methods (Continued):
Efficacy Analysis (Continued):
The secondary Phase 2 efficacy analyses will test (in the following order):  
1) if concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/placebo (Arm B) results in improved Progression-Free survival (PFS) versus 
Arm C; 
2a) if Arm A or 
2b) if Arm B results in improved overall survival (OS) versus Arm C; 
3a) if Arm A or 
3b) if Arm B results in improved overall response rate (ORR) versus Arm C;
4a) if Arm A or 
4b) if Arm B results in improved duration of overall response (DOR) versus Arm C.
Sample Size:
Assuming a hazard ratio of 0.6 for Arm A (Concurrent paclitaxel/carboplatin/radiotherapy/veliparib 
followed by consolidation paclitaxel/carboplatin/veliparib) versus Arm C (Concurrent 
paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo), a 
total of 71 PFS events in Arm A and Arm C combined will provide an expected 95% confidence interval 
of 0.38 to 0.96 for the estimated hazard ratio.  Assuming a hazard ratio of 0.75 for Arm B (Concurrent 
paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/placebo) 
versus Arm C, a total of 107 PFS events will be observed across all three arms at the time when 71 PFS 
events are observed for Arm A and Arm C combined.  A total of approximately 156 subjects (52 subjects 
per treatment arm) will be enrolled into the Phase 2 portion of study to obtain the 107 PFS events.


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1.3
List of Abbreviations and Definition of Terms
Abbreviations
3D
Three Dimensional
ADP
Adenosine Diphosphate
AE
Adverse Event
ALT
Alanine Aminotransferase
ANC
Absolute Neutrophil Count
aPTT
Activated Partial Thromboplastin Time
ASCO
American Society of Clinical Oncology
AST
Aspartate Aminotransferase
BID
Twice a Day
BRCA
Breast Cancer Gene
BUN
Blood Urea Nitrogen
C
Cycle
CBC
Complete Blood Count
CFR
Code of Federal Regulations
CHF
Congestive heart failure
CNS
Central Nervous System
CR
Complete Response
CRF or eCRF
Case Report Form or Electronic Case Report Form
CRT
Chemoradiotherapy
CS
Clinically Significant
CSF
Colony-Stimulating Factor
CT
Computed Tomography
CTEP
Cancer Therapy Evaluation Program
CYP
Cytochrome P450
CYP2C
Cytochrome P450 2C
CYP3A
Cytochrome P450 3A
D
Day
DDI
Drug-Drug Interaction
DLCO
Diffusing Capacity of the Lung for Carbon Monoxide
DLT
Dose Limiting Toxicity
DMC
Data monitoring committee


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DNA
Deoxyribonucleic Acid
DOR
Duration of Overall Response
DSMB
Data and Safety Monitoring Board
ECG
Electrocardiogram
eCRF or CRF
Electronic Case Report Form or Case Report Form
EC
Ethics Committee
ECOG
Eastern Cooperative Oncology Group
EDC
Electronic Data Capture
ERCC1
Excision Repair Cross-Complementary Group 1 Protein
EORTC
European Organization for Research and Treatment of Cancer
EORTC QLQ-C15-PAL
A questionnaire developed by EORTC to assess the quality of life of 
palliative cancer care patients
EORTC QLQ-C30
A questionnaire developed by EORTC to assess the quality of life of cancer 
patients
EORTC QLQ-LC13
A modular supplement questionnaire developed by EORTC for use in lung 
cancer clinical trials
EMA
European Medicines Agency
EMEA
Europe, Middle East and Africa
ESMO
European Society for Medical Oncology
EU
European Union
FDA
US Food and Drug Administration
FEV1
Forced Expiratory Volume in 1 Second (lung airflow measure)
FFPE
Formalin fixed, paraffin embedded
GCP
Good Clinical Practice
G-CSF
Granulocyte Colony-Stimulating Factor
GFR/eGFR
Glomerular Filtration Rate/estimated Glomerular Filtration Rate
Gy
Gray (derived unit of ionizing radiation dose in Radiotherapy)
hCG
Human Chorionic Gonadotropin
ICH
International Conference on Harmonization
ICRU
International Commission on Radiation Units and Measurements
IEC
Independent Ethics Committee
IIA
Investigator Information and Agreement
IIS
Investigator Initiated Studies
IMP
Investigational Medicinal Product
IMRT
Intensity Modulated Radiotherapy


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INR
International Normalized Ratio
IRB
Institutional Review Board
IUD
Intra-Uterine Device
IV, i.v.
Intravenous
IRT
Interactive Response Technology
LD
Longest Diameter
LDH
Lactate Dehydrogenase
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligram
mL
Milliliter
MRI
Magnetic Resonance Imaging
MTD
Maximum Tolerated Dose
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
NCS
Not Clinically Significant
NCI CTCAE
National Cancer Institute Common Terminology Criteria For Adverse Events
NSCLC
Non-small Cell Lung Cancer
ORR
Objective Response Rate
OS
Overall Survival
PAR
Poly-(ADP-ribose)
PARP
Poly-(ADP-ribose)-Polymerase
PBO
Placebo
PD
Pharmacodynamic or Progressive Disease
PET
Positron Emission Tomography
PET CT
Positron Emission Tomography – Computed Tomography
PFS
Progression-Free Survival
PFTs
Pulmonary Function Tests
PG
Pharmacogenetic
pH
Potential Hydrogen (The pH scale measures how acidic or basic a substance 
is)
PK
Pharmacokinetic
PMID
PubMed identifier or PubMed unique identifier
PO
Oral Route of Administration
POR
Proof of Receipt 
PR
Partial Response


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QA
Quality Assurance
QARC
Quality Assurance Review Center
QC
Quality Control
QLQ
Quality of Life Questionnaire
QTc
QT interval corrected for heart rate
QoL
Quality of Life 
RBC
Red Blood Cell
RECIST
Response Evaluation Criteria in Solid Tumors
RPTD
Recommended Phase 2 Dose
RT
Radiotherapy
SAE
Serious Adverse Event
SCLC
Small Cell Lung Cancer
SD
Stable Disease
SGOT
Serum glutamic-oxaloacetic transaminase
SGPT
Serum glutamic-pyruvic transaminase
SmPC
Summary of Product Characteristics
SUSAR
Suspected Unexpected Serious Adverse Reaction
TMZ
Temozolomide
TPN
Total Parenteral Nutrition
TNM 
Tumor size, Nodes and Metastasis presence
ULN
Upper Limit of Normal 
US
Ultrasound or United States
VATS
Video-assisted Thoracoscopic Surgery
W, Wk
Week
WBC
White Blood Cell
WBRT
Whole Brain Radiation Therapy
WJTOG
West Japan Thoracic Oncology Group
XPF
Xeroderma Pigmentosum Group F


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Definition of Terms
ABT-888
Veliparib
AUC
Area under the plasma concentration-time curve
Cmax
Maximum observed plasma concentration
GDSM
Global Drug Supply Management
Tmax
Time to maximum observed plasma concentration


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2.0
Table of Contents
1.0
Title Page ...............................................................................1
1.1
Protocol Amendment:  Summary of Changes ......................................... 2
1.2
Synopsis................................................................................................. 4
1.3
List of Abbreviations and Definition of Terms...................................... 13
2.0
Table of Contents ................................................................ 18
3.0
Introduction......................................................................... 24
3.1
Non-Small Cell Lung Cancer................................................................ 24
3.2
Combined Modality Chemoradiotherapy Therapy ................................ 24
3.3
Paclitaxel/Carboplatin .......................................................................... 25
3.4
PARP Inhibition for Cancer Treatment................................................. 26
3.5
Veliparib .............................................................................................. 27
3.5.1
Rationale for Combining Veliparib with Concurrent
Chemoradiotherapy and Consolidation Chemotherapy.......................... 27
3.5.2
Veliparib Preclinical Toxicology .......................................................... 27
3.5.3
Pharmacokinetics and Pharmacodynamics............................................ 28
3.5.4
Clinical Experience .............................................................................. 29
3.6
Study Rationale .................................................................................... 32
3.7
Differences Statement .......................................................................... 32
3.8
Benefits and Risks................................................................................ 32
4.0
Study Objective ................................................................... 33
5.0
Investigational Plan.............................................................34
5.1
Overall Study Design and Plan:  Description ........................................ 34
5.2
Selection of Study Population............................................................... 34
5.2.1
Inclusion Criteria.................................................................................. 42
5.2.2
Exclusion Criteria................................................................................. 44
5.2.3
Prior and Concomitant Therapy............................................................ 45
5.2.3.1
Prior Therapy ....................................................................................... 45
5.2.3.2
Concomitant Therapy........................................................................... 46
5.3
Efficacy Pharmacokinetic, Pharmacodynamic, Pharmacogenetic 
and Safety Assessments/Variables ........................................................ 48
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ............... 48


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5.3.1.1
Study Procedures.................................................................................. 53
5.3.1.2
Blood Samples for Pharmacogenetic Analysis ...................................... 59
5.3.1.3
Collection and Handling of Pharmacodynamic Variables ..................... 60
5.3.2
Drug Concentration Measurements....................................................... 61
5.3.2.1
Blood Samples for Pharmacokinetic Analysis....................................... 61
5.3.2.2
Measurement Methods ......................................................................... 61
5.3.3
Efficacy Variables................................................................................ 61
5.3.4
Safety Variables ................................................................................... 61
5.3.5
Pharmacokinetic Variables ................................................................... 62
5.3.6
Pharmacogenetic Variables................................................................... 62
5.3.7
Pharmacodynamic Variables ................................................................ 63
5.4
Removal of Subjects from Therapy or Assessment ............................... 64
5.4.1
Discontinuation of Individual Subjects ................................................. 64
5.4.1.1
Discontinuation of Veliparib/Placebo and Paclitaxel/Carboplatin ......... 65
5.4.2
Discontinuation of Entire Study............................................................ 66
5.5
Treatments ........................................................................................... 66
5.5.1
Treatments Administered...................................................................... 66
5.5.1.1
Administration of Veliparib/Placebo (All Subjects) .............................. 68
5.5.1.2
Administration of Paclitaxel, and Carboplatin (All Subjects) ................ 69
5.5.1.3
Thoracic Radiotherapy ......................................................................... 70
5.5.2
Identity of Investigational Products ...................................................... 76
5.5.2.1
Standard of Care Medicinal Products for Study Treatment.................... 76
5.5.2.2
Packaging and Labeling........................................................................ 76
5.5.2.3
Storage and Disposition of Study Drugs ............................................... 77
5.5.3
Method of Assigning Subjects to Treatment Groups ............................. 78
5.5.4
Selection and Timing of Dose for Each Subject .................................... 79
5.5.5
Blinding ............................................................................................... 79
5.5.5.1
Blinding of Investigational Product ...................................................... 79
5.5.5.2
Blinding of Data for Data Monitoring Committee (DMC) .................... 80
5.5.6
Treatment Compliance ......................................................................... 80
5.5.7
Drug Accountability ............................................................................. 81
5.6
Discussion and Justification of Study Design........................................ 82
5.6.1
Discussion of Study Design and Choice of Control Groups .................. 82


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5.6.2
Appropriateness of Measurements........................................................ 83
5.6.3
Suitability of Subject Population .......................................................... 83
5.6.4
Selection of Doses in the Study ............................................................ 83
6.0
Adverse Events .................................................................... 84
6.1
Definitions ........................................................................................... 85
6.1.1
Adverse Event...................................................................................... 85
6.1.2
Serious Adverse Events........................................................................ 86
6.2
Adverse Events Expected Due to NSCLC or Progression of 
NSCLC ................................................................................................ 87
6.3
Adverse Event Severity ........................................................................ 87
6.4
Relationship to Study Drug................................................................... 88
6.5
Adverse Event Collection Period.......................................................... 89
6.6
Adverse Event Reporting...................................................................... 89
6.6.1
Deaths.................................................................................................. 89
6.6.2
Lack of Efficacy or Worsening of Disease............................................ 90
6.6.3
Reporting Serious Adverse Events........................................................ 90
6.7
Pregnancy............................................................................................. 92
6.8
Toxicity Management........................................................................... 93
6.8.1
Dose Limiting Toxicities ...................................................................... 93
6.8.2
Determination of the MTD ................................................................... 94
6.8.3
Determination of the RPTD.................................................................. 94
6.8.4
Dose Modifications During Concurrent Therapy .................................. 95
6.8.4.1
Dose Modifications for Hematologic Toxicity ...................................... 95
6.8.4.2
Dose Modifications for Non-hematologic Toxicity............................... 96
6.8.4.3
Dose Modifications for In-Field, Non-Hematologic Toxicity 
During Concurrent Therapy.................................................................. 96
6.8.5
Dose Modifications During Consolidation Therapy .............................. 97
6.8.5.1
Veliparib Dose Reductions and Delays ................................................. 97
6.8.5.2
Paclitaxel/Carboplatin Dose Reductions and Delays ............................. 98
7.0
Protocol Deviations ........................................................... 100
8.0
Statistical Methods and Determination of Sample 
Size ..................................................................................... 100
8.1
Statistical and Analytical Plans............................................................100


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8.1.1
Baseline Characteristics.......................................................................101
8.1.1.1
Demographics .....................................................................................101
8.1.1.2
Medical History...................................................................................101
8.1.2
Efficacy Endpoints ..............................................................................102
8.1.2.1
Primary Efficacy Endpoint ..................................................................102
8.1.2.2
Secondary Efficacy Endpoints.............................................................102
8.1.2.3
Tertiary Efficacy Endpoints.................................................................103
8.1.3
Primary Analysis of Efficacy...............................................................103
8.1.4
Secondary Analysis of Efficacy...........................................................104
8.1.5
Tertiary Analysis of Efficacy...............................................................104
8.1.6
Safety Assessments .............................................................................105
8.1.6.1
Duration of Study Drug .......................................................................105
8.1.6.2
Adverse Event.....................................................................................105
8.1.6.3
Serious Adverse Event.........................................................................106
8.1.6.4
Death...................................................................................................106
8.1.6.5
Longitudinal Analyses of Laboratory and Vital Signs Data..................106
8.1.6.6
Analyses of Laboratory Data Using NCI CTCAE................................107
8.1.6.7
Analyses of Vital Signs Using Criteria for Potentially Clinically 
Significant Vital Sign Values...............................................................107
8.1.7
Timing of Efficacy Analyses and Safety Evaluations...........................108
8.1.8
Interim Analysis..................................................................................108
8.2
Determination of Sample Size .............................................................108
8.3
Randomization Methods......................................................................109
9.0
Ethics.................................................................................. 109
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) ........................................................................................109
9.2
Ethical Conduct of the Study...............................................................110
9.3
Subject Information and Consent.........................................................110
10.0
Source Documents and Case Report Form 
Completion ........................................................................ 111
10.1
Source Documents...............................................................................111
10.2
Case Report Forms ..............................................................................112
11.0
Data Quality Assurance .................................................... 113


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12.0
Use of Information ............................................................ 113
13.0
Completion of the Study ................................................... 113
14.0
Investigator's Agreement.................................................. 115
15.0
Reference List.................................................................... 116
List of Tables
Table 1.
Dose Escalation.................................................................................... 35
Table 2.
Study Activities (Phase 1 and 2) ........................................................... 49
Table 3.
Schedule of Pharmacogenetic and Pharmacodynamic Assessments ...... 52
Table 4.
Pharmacokinetic Assessments (Phase 1)............................................... 52
Table 5.
Schedule of Pharmacokinetic Assessments (Phase 2)............................ 53
Table 6.
Clinical Laboratory Tests ..................................................................... 57
Table 7.
Identity of Investigational Product........................................................ 76
Table 8.
Standard of Care Medicinal Products for Study Treatment.................... 76
Table 9.
Study Drug Storage Conditions ............................................................ 77
Table 10.
Suggested Guidelines for Veliparib + Paclitaxel/Carboplatin 
Independent Dose Reduction ................................................................ 97
List of Figures
Figure 1.
Phase 1 Study Schematic ...................................................................... 38
Figure 2.
Phase 2 Study Schematic ...................................................................... 40
Figure 3.
Adverse Event Collection..................................................................... 89
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator.........................................119
Appendix B.
List of Protocol Signatories .................................................................121
Appendix C.
Adverse Events Expected Due to NSCLC or Progression of 
NSCLC ...............................................................................................122
Appendix D.
Suggested Guidelines for Paclitaxel/Carboplatin Dose Delay or 
Reduction During Consolidation Chemotherapy..................................124
Appendix E.
RECIST Version 1.1 for Tumor Response (PFS).................................125


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Appendix F.
Protocol Amendment:  List of Changes ...............................................132


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3.0
Introduction
3.1
Non-Small Cell Lung Cancer
Lung cancer is the most common cancer with an estimated 1.8 million new cases globally 
in 2012, accounting for approximately 13% of the global cancer burden.  It is also the 
most common cause of cancer-related death worldwide with an estimated 1.6 million 
annual deaths and mortality to incidence rate of 0.87.  Most lung carcinomas are 
diagnosed at an advanced stage, conferring poor prognosis.1
Non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancer 
cases, and it includes two major types:  1) non-squamous (including adenocarcinoma, 
large-cell carcinoma, and other cell types); and 2) squamous cell (epidermoid) carcinoma.  
The incidence of NSCLC increases with age; 60% occur in patients aged 60 years and 
older, and 30% to 40% in patients aged 70 years and older.  Surgery, radiotherapy, and 
chemotherapy, either alone or in combination, are the modalities commonly used to treat 
NSCLC patients.  Thirty-Five to 40 percent of NSCLC patients have locally advanced and 
inoperable disease, for which concurrent chemoradiotherapy is commonly utilized.2  
Despite improvements in the treatment of locally advanced NSCLC, long-term survival is 
achieved in less than 25% of patients.  Thus, there is a major need to identify therapies 
with improved outcome in this clinical setting.2,3
3.2
Combined Modality Chemoradiotherapy Therapy
Combined modality chemoradiotherapy is standard of care for the treatment of patients 
with inoperable or locally advanced NSCLC.  In 1980, radiotherapy for subjects with 
locally advanced NSCLC was shown to confer a median survival of 10 months and 5-year 
survival of 5%.4  The survival benefit of adding chemotherapy to radiation was 
subsequently established in multiple Phase 3 trials.  Beginning in 1996, trials showed that 
cisplatin-based induction chemotherapy followed by conventional RT 
(60 Gy/approximately 30 fractions) resulted in better survival than conventional RT 
alone.5-8  Later randomized trials established concurrent chemotherapy and radiation to be 


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superior to sequential administration.  In RTOG 9410, concurrent administration of 
cisplatin/vinblastine and RT was superior to the same regimen given sequentially (median 
survival of 17.0 versus 14.6 months).  The LAMP (Locally Advanced Multi-modality 
Protocol) Phase 2 study, compared i) induction paclitaxel/carboplatin/followed by RT, 
versus ii) induction paclitaxel/carboplatin followed by concurrent RT + weekly 
paclitaxel/carboplatin, versus iii) concurrent RT + weekly paclitaxel/carboplatin followed 
by consolidation paclitaxel/carboplatin.9  Median overall survival was 13, 12.7, and 
16.3 months in the three arms respectively.  In a more recent study, RTOG 0617, 
concurrent RT + paclitaxel/carboplatin followed by consolidation paclitaxel/carboplatin 
were administered with high (74 Gy) versus low (60 Gy) dose RT.  Median overall 
survival was 23.5 months in the 60 Gy arm, while no benefit of higher dose radiation was 
seen.10  Principle toxicities associated with concurrent therapy in these trials were 
esophagitis and pneumonitis.  In a multi-arm conducted by the West Japan Thoracic 
Oncology Group (WJTOG), concurrent RT + weekly paclitaxel/carboplatin followed by 
consolidation paclitaxel/carboplatin resulted in similar survival and less toxicity versus 
concurrent RT + MVP (mitomycin, vendesine, cisplatin) followed by MVP consolidation 
(PMID# 20625120).11
3.3
Paclitaxel/Carboplatin
Carboplatin is a commonly used platinum compound that acts by producing interstrand 
deoxyribonucleic acid (DNA) cross-links and, thus, interrupting cell division.  It is 
approved by the Food Drug Administration (FDA) for the treatment of ovarian cancer and 
by the European Medicines Agency (EMA) for ovarian cancer of epithelial origin and 
small cell lung carcinoma.  It is also used for the treatment of non-small cell lung cancer 
(NSCLC), head and neck cancer, endometrial cancer, metastatic seminoma, and more 
recently in breast cancer.  Carboplatin is eliminated by renal excretion and the clearance is 
related to the glomerular filtration rate (GFR).  Therefore, it is dosed on the basis of GFR 
and the target area under the concentration versus time curve (AUC).  Myelosuppression 
is the dose limiting toxicity of carboplatin and is dose dependent.  Anemia may be 
cumulative and require transfusion support with prolonged therapy.  Anaphylactic-like 


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reactions to carboplatin have been reported and may occur within minutes of carboplatin 
administration.  The risk of allergic reactions is increased in patients previously exposed 
to platinum therapy.  Other toxicities include nausea, vomiting, renal toxicity, and 
neurotoxicity.
Paclitaxel promotes the assembly of microtubule formation and stabilizes them by 
preventing depolymerization.  It is insoluble in water and, therefore, is formulated in 
cremophor.  Paclitaxel is approved by the FDA for the treatment of breast cancer, 
non-small cell lung cancer, ovarian cancer, and Kaposi's sarcoma.  It is also in use for the 
treatment of several other solid tumor malignancies.  It is administered as an intravenous 
(IV) infusion and can be used either on an every 3-week schedule or a weekly schedule.  
Main toxicities associated with the use of paclitaxel are myelosuppression, 
myalgias/arthralgias, and sensory neuropathy.  Hypersensitivity reactions requiring 
treatment have occurred in 2% to 4% of patients receiving paclitaxel in clinical trials; 
thus, patients should be pretreated with corticosteroids, diphenhydramine, and H2 
antagonists.
Paclitaxel/Carboplatin is one of several common chemotherapy backbones recommended 
for use in chemoradiotherapy regimens for Stage III NSCLC.12,13
3.4
PARP Inhibition for Cancer Treatment
Poly(ADP-ribose)-polymerase (PARP) 1 and 2 are nuclear enzymes that recognize 
deoxyribonucleic acid (DNA) damage and facilitate DNA repair.14  Inactive PARPs 1 and 
2 bind to damaged DNA, which leads to their auto-activation.  The resulting activated 
PARP enzymes then poly(ADP-ribosyl)ate many nuclear target proteins, including those 
that facilitate DNA repair of both single-stranded or double-stranded DNA breaks.  Thus 
PARP inhibition will result in less efficient DNA repair following a cytotoxic insult.
DNA damaging agents including cytotoxic chemotherapy and radiotherapy, remain a 
mainstay of treatment for many patients with cancer.  Since cancer cells are genetically 
unstable, often exhibiting complex karyotypes that include large deletions, insertions, and 


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unbalanced translocations of chromosomal material, these cells are more susceptible than 
normal tissues to cytotoxicity induced by DNA-damaging agents.15  Of these, deficiencies 
in mismatch repair or homologous recombination are associated with the largest number 
of malignancies.  These deficiencies render cells more dependent on PARP for DNA 
repair, and hence more sensitive to PARP inhibition.16
PARP enabled DNA repair may also compensate for the loss of other repair pathways.  
Higher expression of PARP in cancer cells compared to normal cells has been linked to 
drug resistance and the overall ability of cancer cells to sustain genotoxic stress.17
3.5
Veliparib
A detailed discussion of the preclinical toxicology, metabolism, and pharmacology can be 
found in the veliparib Investigator's Brochure.17
3.5.1
Rationale for Combining Veliparib with Concurrent 
Chemoradiotherapy and Consolidation Chemotherapy
Administration of veliparib in vitro or in vivo inhibits the formation of poly (ADP-ribose) 
(PAR) polymers.  When veliparib and DNA-damaging cytotoxic agents or 
DNA-damaging radiation are co-administered, veliparib inhibits the repair of DNA.  In a 
variety of nonclinical tumor models, including lung, melanoma, breast, prostate, colon, 
and glioma, veliparib significantly enhanced the antitumor activity when dosed on a 
schedule that overlapped the administration of a DNA-damaging therapy.
3.5.2
Veliparib Preclinical Toxicology
The toxicological profile of veliparib has been evaluated in nonclinical general toxicity 
studies that included single-dose (rats and mice), repeat-dose (duration of up to 6 months 
in rats and up to 9 months in dog), reproductive (embryofetal development in rat and 
rabbit), genetic (Ames, in vitro cytogenetics, in vivo micronucleus), phototoxicity (in 
vitro photosensitivity) and juvenile rat toxicity studies.  Primary nonclinical findings 
included effects on the central nervous system (CNS) (convulsions, tremors), 
hematopoietic system (bone marrow depletion and resultant decreased circulating white 


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and red blood cells), reproductive system (male germ cell depletion, female reproductive 
tract tissues degeneration), and lymphoid tissues (lymphocyte depletion), with lesser 
effects on the gastrointestinal tract (single-cell necrosis) and cardiovascular system 
(10% QTc interval prolongation).  Convulsions and other CNS-related signs were 
considered exposure-dependent, and were generally self-limiting, ameliorated by dose 
reduction or cessation of dosing, or responsive to treatment.  All other findings were dose 
dependent and reversible upon discontinuation of veliparib administration.  Veliparib was 
also genotoxic (induced chromosomal aberrations in vitro and increased micronuclei 
formation in vivo) and was toxic to the developing fetus (increases in the incidence of 
fetal external/visceral/skeletal malformations/variations) in rats and rabbits.  Veliparib 
demonstrated no phototoxic potential in the photosensitivity assay.  With the exception of 
CNS and cardiovascular effects, the toxicity of veliparib is generally consistent with the 
pharmacology of the compound.
3.5.3
Pharmacokinetics and Pharmacodynamics
The pharmacokinetic exposure of veliparib is approximately dose-proportional over 10 
through 500 mg BID dose range.  The absorption of veliparib after oral dosing is 
relatively fast where veliparib plasma concentrations peak at approximately 1 to 2 hours 
after dosing across dose levels.  The terminal half-life (t1/2) of veliparib is about 6 hours, 
with minimal accumulation following multiple BID dosing.  Food does not have a 
significant effect on veliparib bioavailability.  The administration of a high-fat meal had 
no significant effect on AUC and only caused a slight decrease in veliparib Cmax (17%) 
and a delay of approximately 1 hour in Tmax.  The mean urinary recovery of unchanged 
veliparib was 73% and the total urinary recovery of veliparib (as parent compound and 
M8 metabolite) was 90%, which indicates that renal excretion is a major pathway in 
veliparib elimination.  Veliparib is not a potent inhibitor, nor an inducer, of the major 
human cytochrome P450s (CYPs), suggesting a minimal potential for DDIs at the 
anticipated therapeutic concentrations.  Potential drug-drug interactions (DDI) of veliparib 
are being evaluated in veliparib combination studies.  There was no significant 
pharmacokinetic interaction between veliparib and temozolomide (TMZ), between 


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veliparib and carboplatin/paclitaxel (C/P), between veliparib and folinic acid, fluorouracil, 
and irinotecan (FOLFIRI), and between veliparib and capecitabine/5-fluorouracil (5-FU).  
Preliminary results also indicate the absence of a DDI between veliparib and 
carboplatin/gemcitabine and between veliparib and carboplatin/etoposide.  
3.5.4
Clinical Experience
Veliparib is investigated in AbbVie-sponsored studies, in Investigator initiated studies 
(IIS), and in CTEP-sponsored studies.  In these studies, veliparib is administered as 
monotherapy, combined with a variety of chemotherapeutic agents, or combined with 
radiotherapy.
Summary preliminary or final efficacy data from AbbVie sponsored studies show that 
veliparib has activity in combination with TMZ, with radiotherapy, and with 
carboplatin + paclitaxel.18  Data from non-AbbVie sponsored studies show veliparib has 
activity as monotherapy for treatment of ovarian cancer19 and activity in combination with 
carboplatin + paclitaxel for treatment of early breast cancer.20  Veliparib is currently in 
Phase 2 clinical development in combination with several DNA-damaging agents across a 
variety of cancer indications and Phase 3 clinical development in combination with 
carboplatin and paclitaxel for early breast cancer and for advanced/metastatic squamous 
NSCLC.  At present, AbbVie's safety database for veliparib is based on the exposure of 
approximately 2000 cancer patients to veliparib in clinical studies.  Veliparib's known and
potential safety risks were identified based on clinical safety analyses, as well as 
evaluation of pharmacological mechanism, preclinical studies, and literature.  Identified 
risks associated with veliparib administration are hematological cytopenias when veliparib 
is added to backbone chemotherapy regimens.  Most observed toxicities in patients 
exposed to veliparib have been as expected with DNA-damaging agents and are 
manageable with routine oncology supportive care.  Potential risks of veliparib 
administration, identified mostly in preclinical studies or based on pharmacological 
mechanism, but not confirmed in clinical studies, are seizures, changes in testes/ovaries, 
and toxicity to the developing fetus.  A potential risk of secondary malignancies is 
theoretical based on veliparib's mechanism of action.


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Veliparib and Radiotherapy
Study M10-128 was a Phase 1, open-label dose escalation study evaluating the safety, 
tolerability and pharmacokinetics of veliparib in combination with whole brain radiation 
therapy (WBRT) in subjects with brain metastases.  Doses of 200 mg or less were 
tolerated and were not associated with toxicity above that attributable to WBRT alone.  
G3/4 adverse events in 5% or more of treated subjects (N = 81) included fatigue (7.4%) 
and hyponatremia (6.2%).  The median survival of subjects with brain metastases from 
NSCLC was 10.0 months.  Based on these results, AbbVie is conducting a randomized 
Phase 2 study investigating veliparib in combination with whole brain radiation therapy 
for subjects with brain metastases from NSCLC.
Study M12-95021 was a Phase 1b study investigating veliparib in combination with 
capecitabine and radiation in subjects with locally advanced rectal cancer.  In this study, 
veliparib was dose-escalated and well-tolerated in 32 subjects including 16 at the 
maximum administered dose of 400 mg BID.  The MTD was not reached based on the 
study design.  Dose-limiting toxicities occurred in 2 subjects:  grade 2 radiation skin 
injury in a 70 mg BID subject and grade 2 nausea and vomiting in a 400 mg BID subject.  
None of these events were serious adverse events.  Overall, treatment-emergent adverse 
events reported for ≥ 25.0% of the 32 subjects were nausea (53.1%), diarrhea (50.0%), 
fatigue (50.0%), radiation skin injury (28.1%), constipation (25.0%), and vomiting 
(25.0%).  Similar results were observed for treatment emergent adverse events considered 
possibly or probably related to study drug.  These events are consistent with the known 
adverse event profile of capecitabine and/or radiation treatment.
Overall, 8 subjects experienced at least 1 grade 3 treatment-emergent adverse event.  The 
only grade 3 adverse event experienced by more than 1 subject was diarrhea (1 [14.3%] of 
7 subjects in the > 70 – < 400 mg BID group, 2 [12.5%] of 16 subjects in the 400 mg BID 
group).  There were no grade 4 treatment-emergent adverse events in this study.
Veliparib in combination with capecitabine and radiation showed promising preliminary 
antitumor activity.  Complete response was achieved in 4 of 16 subjects (25.0%) who 


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received < 400 mg BID of veliparib and 5 of 15 subjects (33.3%) who received veliparib 
400 mg BID and had a postsurgery assessment.  The majority of subjects in each dose 
group achieved tumor downstaging (12 of 16 subjects [75.0%] for < 400 mg BID, 12 of 
15 subjects [80.0%] for 400 mg BID) and had a reduction of ≥ 50% in their CEA value 
relative to baseline (12 of 16 subjects [75.0%] for < 400 mg BID, 9 of 15 subjects [60.0%] 
for 400 mg BID).  The majority of subjects underwent sphincter-sparing surgery (11 of 
16 subjects [68.8%] for < 400 mg BID, 12 of 15 subjects [80.0%] for 400 mg BID).
Veliparib and Paclitaxel/Carboplatin for NSCLC
Phase 1 data from patients treated with veliparib, carboplatin, and paclitaxel for advanced 
NSCLC are available from CTEP Study 7967.21  Subjects had advanced solid tumors, 
received ≤ 3 prior chemotherapy regimens for advanced disease, and had ECOG 
performance status 0 to 2.  Veliparib was given on Days 1 to 7 of each 21-day cycle, and 
paclitaxel and carboplatin were administered on Day 3.  Two DLTs (febrile neutropenia 
and hyponatremia) were observed in 2 of 7 evaluable subjects treated at the maximum 
tolerated dose of veliparib 120 mg BID, paclitaxel 200 mg/m2, and carboplatin AUC 6.  
The most common AEs reported in this study were neutropenia and fatigue (reported in 
> 50% of subjects); nausea, thrombocytopenia, and peripheral sensory neuropathy 
(> 40% of subjects); and anemia, constipation, alopecia, diarrhea, decreased appetite, 
lymphopenia, and myalgia (> 20% of subjects).  Among 68 initial patients, partial 
responses were seen in 11 patients and complete response in 2 patients.  Among 
11 subjects with NSCLC (8 evaluable), 4 subjects had responses and 3 additional subjects 
had stable disease at first tumor evaluation.  A double-blind, randomized Phase 2 study of 
carboplatin and paclitaxel with veliparib or placebo for subjects with advanced NSCLC is 
ongoing.  Therapy is delivered for up to 6 cycles with carboplatin AUC 6 (IV) and 
paclitaxel 200 mg/m2 (IV) every 3 weeks plus veliparib/placebo 120 mg BID (PO) on 
seven days around chemotherapy administration.  All subjects have completed therapy, 
and final data are pending.  Preliminary data showed an improvement in median 
progression-free survival of approximately 1.6 months  and an improvement in overall 
survival of approximately 2 months among NSCLC subjects treated with veliparib 


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(differences not statistically significant; unpublished data on file at AbbVie).  Leukopenia 
was increased in frequency by < 15% for veliparib versus placebo-treated subjects, and 
neutropenia was increased in frequency by < 10% for veliparib versus placebo-treated 
subjects.  No other AE was increased by > 5%.  AEs led to reduction or discontinuation of 
backbone therapies at similar rates (± 4%) with or without veliparib.  Based on these data, 
AbbVie is conducting additional studies of veliparib in combination with 
paclitaxel/carboplatin for patients with advanced/metastatic NSCLC.
3.6
Study Rationale
A moderate proportion of NSCLC patients are diagnosed with Stage III disease, for which 
multi-modality therapy is recommended and prognosis is poor.  Current standard therapy 
for Stage III NSCLC provides time-to-progression of 1 – 1.5 years.5-10  Phase 1 data and 
preliminary Phase 2 data described above suggest the addition of veliparib to 
radiotherapy, paclitaxel and carboplatin may improve outcome of patients with NSCLC.  
This study will investigate concurrent radiotherapy and consolidation chemotherapy with 
veliparib for Stage III NSCLC.
3.7
Differences Statement
The current study (Study M14-360) is the first AbbVie-sponsored study investigating the 
efficacy and tolerability of veliparib in combination with paclitaxel/carboplatin-based 
chemoradiotherapy followed by consolidation paclitaxel/carboplatin in subjects with 
locally advanced Stage III non-small cell lung cancer.
3.8
Benefits and Risks
This study proposes to establish improved clinical outcomes for patients with Stage III 
NSCLC through the addition of veliparib to standard treatment with radiotherapy, 
carboplatin and paclitaxel.  Preclinical data demonstrate that veliparib potentiates the 
anti-tumor activity of radiation and platinums, and data from early-phase studies 
(completed or preliminary) is consistent with these observations.  As described below, 
subjects with advanced or metastatic NSCLC receiving veliparib with carboplatin and 


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paclitaxel have shown favorable, though not statistically significant, results for the 
endpoints of overall survival; and subjects with brain metastases from NSCLC receiving  
veliparib with radiotherapy (single arm study) had longer than expected survival.
Risks in this study include toxicity from the addition of veliparib to standard therapy.  
Preliminary safety data from a blinded, randomized Phase 2 study of carboplatin, 
paclitaxel, and veliparib in subjects with advanced NSCLC suggest low rates of additional 
toxicities and no compromise to the delivery of carboplatin and paclitaxel.  Safety data 
from a single arm Phase 1 study of radiotherapy and veliparib in subjects with NSCLC 
brain metastases show minimal additional toxicities and no compromise to the delivery of 
radiation.  Standard clinical practices to manage the toxicity of chemoradiotherapy and 
consolidation chemotherapy are well established.  Other potential risks of veliparib 
administration, identified in preclinical studies or based on pharmacological mechanism, 
but not confirmed in clinical studies must also be considered.  These risks include 
seizures, changes in testes/ovaries, toxicity to the developing fetus and secondary 
malignancies.
4.0
Study Objective
The primary objectives of the study are to establish the recommended Phase 2 dose 
(RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based 
chemoradiotherapy (CRT) and paclitaxel/carboplatin-based consolidation 
chemoradiotherapy and to assess whether the addition of oral veliparib versus placebo to 
paclitaxel/carboplatin-based chemoradiotherapy with consolidation paclitaxel/carboplatin 
will improve progression-free survival (PFS) in patients with Stage III non-small cell lung 
cancer (NSCLC).
The secondary objectives of the study are to assess overall survival (OS), objective 
response rate (ORR), duration of overall response (DOR), safety and tolerability of 
veliparib versus placebo added to standard therapy.


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The tertiary objectives are to assess Quality of Life (QoL) and ECOG performance status.  
In addition, biomarkers including, but not limited to, defects in DNA-repair genes will be 
assessed in correlation with safety and efficacy data.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This two-phase study consists of 1) dose-escalation of veliparib to determine an RPTD for 
combination with concurrent paclitaxel/carboplatin-based CRT and paclitaxel/carboplatin-
based consolidation chemoradiotherapy; and 2) a randomized, double-blinded study to 
determine whether veliparib improves outcome relative to placebo when added to 
paclitaxel/carboplatin based CRT followed by consolidation paclitaxel/carboplatin in 
subjects with previously untreated Stage III NSCLC.
5.2
Selection of Study Population
The study was designed to enroll approximately 206 subjects with Stage III NSCLC 
(approximately 50 in the dose escalation portion and approximately 156 in the 
randomized portion) at approximately 50 – 75 study centers to meet scientific and 
regulatory objectives without enrolling an undue number of subjects in alignment with 
ethical considerations.  Therefore, if the target number of subjects has been enrolled, there 
is a possibility that additional subjects in Screening will not be enrolled.
Dose Escalation Portion (Phase 1)
In the dose escalation phase (Phase 1) of the study, subjects will receive veliparib in 
combination with carboplatin AUC 2+ paclitaxel 45 mg/m2 + thoracic radiotherapy.  
Radiation delivery will be over no more than 9 weeks by 3-dimensional conformal 
radiotherapy or intensity modulated radiotherapy (IMRT), and the total dose will be 
60 – 63 Gy.  Dose escalation of veliparib during chemoradiotherapy will occur in cohorts 
derived from the 3 + 3 design described in Section 5.5.1.  The first cohort of at least 3 –
6 subjects will receive veliparib 60 mg BID throughout CRT.  Additional eligible subjects 


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may be enrolled at the current dose level at the discretion of the Investigators and the 
AbbVie Medical Monitor.  Based on tolerability, subsequent cohorts will receive doses of 
veliparib as shown in Table 1.
Table 1.
Dose Escalation
Dose Escalation in the Concurrent Chemoradiotherapy
Cohort
Dose Level
Number of Subjects
Veliparib (mg)
1
1
3 – 6
60
2
2
3 – 6
80
3
3
3 – 6
120
4
4
3 – 6
200
5
5
3 – 6
240
–1
0 – 6
40
Dose Escalation in the Consolidation Chemotherapy
Cohort
Dose Level
Number of Subjects
Veliparib (mg)
1 – 5
3 – 6
120
6
3 – 6
240
To insure subject safety during the Phase 1 portion of the study, other doses may be 
selected for investigation based on cumulative safety data with agreement between the 
investigators and medical monitor.  Veliparib doses will be escalated or reduced by 
multiples of 20 mg (the tablet size) based on review of the cumulative experience in prior 
cohorts with the Phase 1 Investigators.  Also, no dose level will exceed the prior dose by 
> 67%, and no dose above 240 mg will be given.
Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new 
dosing cohort is opened or until the RPTD is identified.  During CRT dose escalation, the 
DLT period for each subject will be from the start of veliparib dosing through 28 days 
following completion of RT or until consolidation chemotherapy is initiated, and the DLT 
period for all subjects at each dose level will end upon initiation of the next dose level.  


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CRT dose escalation will occur with a consolidation dose of veliparib of 120 mg BID + 
carboplatin (AUC 6 mg/mL/min) + paclitaxel (200 mg/m2) for up to two 21-day cycles.  
Once the concurrent CRT RPTD is identified, an additional cohort will be enrolled to 
explore the tolerability of a consolidation dose of veliparib at 240 mg BID + carboplatin 
(AUC 6 mg/mL/min) + paclitaxel (200 mg/m2) for up to two 21-day cycles.  
Subjects overenrolled in Cohort 5 will be allowed to roll over into Cohort 6 as long as 
they have not started the consolidation phase, and at the discretion of the Investigators and 
the AbbVie Medical Monitor.
For Cohort 6, the DLT period will be 21 days from start of consolidation chemotherapy or 
until the start of Cycle 2 consolidation therapy. 
For this cohort, if 3 or less subjects were able to take Cycle 2 of consolidation 
chemotherapy, the reason of dose reduction and treatment discontinuation will be 
reviewed as part of consideration to determine MTD/RPTD of veliparib for the 
consolidation phase.
DLTs are defined as the following events that are considered by the investigator group to 
be related to treatment:
1.
Radiation induced Grade 3 or greater cardiac toxicity (e.g., myocarditis, 
pericarditis, heart failure, ventricular dysfunction, myocardial infarction). 
2.
Radiation induced myelopathy/myelitis (does not include L'Hermitte's syndrome).
3.
Radiation-related pneumonitis resulting in delay in radiotherapy, chemotherapy 
(CRT or consolidation) or veliparib of more than 3 weeks or early discontinuation 
of RT (total dose < 50 Gy).
4.
G4 or greater esophagitis or esophagitis, dysphagia, and odynophagia requiring 
treatment interruption of > 7 days despite medical management.
5.
G2 or greater seizure.


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M14-360 Protocol Amendment 4
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6.
Grade 4 or greater neutropenia for > 7 days or neutropenic fever (defined as ANC 
< 500 and a temperature of 38.5°C or above).
7.
Grade 4 or greater thrombocytopenia.
8.
Grade 4 diarrhea or nausea/vomiting despite appropriate antiemetic therapy lasting 
> 48 hours.
9.
Any other toxicity resulting in delay in radiotherapy, chemotherapy, or veliparib of 
more than 14 days or early discontinuation of RT (total dose < 50 Gy).
10.
All other non-hematologic toxicities of Grade 3 or greater, with the following 
exceptions:
a.
Anorexia
b. Fatigue
c.
Grade 3 infection
d. Grade 3 AST/ALT elevations ≤ 7 days
e.
Infusion reactions.  Patients with Grade 3 or worse infusion reactions will be 
removed from study and replaced and will not be considered evaluable for DLT
f.
Grade 3 or 4 lymphopenia
g. Grade 3 or 4 electrolyte abnormalities that are corrected to Grade 2 or less in less 
than 48 hours
A schematic of the Phase 1 treatment is shown in Figure 1.


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Figure 1.
Phase 1 Study Schematic


Veliparib
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Randomized Phase 2 Portion
Following the dose escalation portion of the study, the RPTD will be determined by the 
sponsor and at the discretion of the sponsor, the Phase 2 portion of the study will begin 
with patient randomization in a 1:1:1 ratio to the treatment arms as follows:
A. Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by 
consolidation paclitaxel/carboplatin/veliparib
B. Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by 
consolidation paclitaxel/carboplatin/placebo
C. Concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation 
paclitaxel/carboplatin/placebo
Subject randomization will be stratified by tumor volume (≤ 90 versus > 90 cm3) and 
smoking history (current smoker versus former smoker versus never smoked).
A schematic of the Phase 2 treatment arms is shown in Figure 2.


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Figure 2.
Phase 2 Study Schematic


Veliparib
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41
Screening procedures, QoL assessments, and baseline radiographic tumor assessments 
will be performed within 28 days prior to randomization.
Subjects who experience toxicities due to carboplatin, paclitaxel, radiotherapy, or 
veliparib/placebo may require a delay in the dosing schedule or a dose modification as 
described in Appendix D.  Subjects without clinical progression of disease and with 
tolerable side effects should continue to receive treatment until completion of all 
prescribed cycles (chemoradiotherapy plus 2 cycles of consolidation chemotherapy).
Radiographic tumor assessments will be conducted at baseline, prior to consolidation 
chemotherapy, at 24 weeks after start of treatment, every 8 weeks until one year after 
beginning therapy, then every 12 weeks.  Radiographic progression will be determined 
using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 beginning 
with the second scan after completion of CRT).  RECIST criteria can be found in 
Appendix E.  Clinical progression prior to that time will be determined by the 
investigator.  In Phase 2 portion of the study, a QoL assessment as measured by the 
EORTC QLQ-C15-PAL and the companion symptom module EORTC QLQ-LC13 will 
be performed at screening, prior to consolidation chemotherapy, at 24 weeks after start of 
treatment, every 8 weeks until one year after beginning therapy and at the final visit.
After completion of protocol therapy, subjects will be observed without further therapy 
until progression.  The visit at which an investigator identifies disease progression or at 
which a subject meets other criteria for study discontinuation will be considered the final 
visit.  Criteria for discontinuation can be found in Section 5.4.  
All subjects with a final visit < 30 days after the last dose of drug will have 
one Follow-Up Visit approximately 30 days after the Final Visit.  If a subject is 
discontinued from the study with an ongoing adverse event or an unresolved clinically 
significant laboratory result, the site will attempt to provide follow-up until a satisfactory 
clinical resolution of the laboratory results or adverse event is achieved.


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Overall survival (OS) will be determined by the Investigator until radiographic 
progression.  After radiographic progression, survival information will be collected via the 
electronic CRF at 8 week intervals (or as requested by sponsor to support data analysis).
Details regarding study visits and study procedures mentioned above can be found in 
Section 5.3.1.1 and in Table 2.
5.2.1
Inclusion Criteria
1.
Subject must be ≥ 18 years of age;
2.
Subject must have histologically or cytologically confirmed Stage III NSCLC.  
When pleural fluid is visible on the CT scan or on a chest x-ray, a thoracentesis is 
required to confirm that the pleural fluid is serous AND cytologically negative.  
Effusions that are minimal (i.e., not visible on chest x-ray) or that are too small to 
safely tap are exempted from the requirement for thoracentesis. 
3.
Subjects in the randomized portion of the study must have measurable disease as 
per the RECIST version 1.1 criteria;
4.
Subject must consent to provide archived tissue or cytology sample of NSCLC 
lesion for analysis;
5.
Subjects must have V20 (volume of lung to receive 20 Gy radiotherapy according 
to simulation) < 35%;
6.
Subject must have an Eastern Cooperative Oncology Group (ECOG) performance 
score of 0 – 1;
7.
Subject must have adequate hematologic, renal, hepatic, and lung function as 
follows:
●
Bone marrow:  Absolute Neutrophil count (ANC) ≥ 1,500/μL; Platelets 
≥100,000/mm3; Hemoglobin ≥ 9.0 g/dL (without transfusion);
●
Renal function:  Calculated creatinine clearance ≥ 50 mL/min by the 
Cockcroft-Gault formula;


Veliparib
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●
Hepatic function and enzymes:  aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) ≤ 2.5 × the upper limit of normal (ULN) of 
institution's normal range; Bilirubin ≤ 1.5 × ULN; subjects with Gilbert's 
syndrome may have a bilirubin ≥ 1.5 × ULN of central laboratory normal 
range; 
●
Pulmonary function tests (PFTs) including FEV1 within 12 weeks prior to 
randomization; for FEV1, the best value obtained pre- or post-bronchodilator 
must be ≥ 1.2 liters/second and/or ≥ 50% predicted.
8.
Female subjects of childbearing potential (i.e., those who are not postmenopausal 
for at least 1 year or surgically sterile by bilateral tubal ligation, bilateral 
oophorectomy or hysterectomy) and their male partner should practice at least 
one of the methods of birth control listed below for at least 6 months after 
treatment with chemotherapy.  Male subjects and their female partners of 
childbearing potential should practice at least one of the methods of birth control 
listed below for at least 6 months after treatment with chemotherapy.
●
Total abstinence from sexual intercourse (if it is the subject's preferred and 
usual lifestyle; beginning a minimum one complete menstrual cycle prior to 
study drug administration and to extend 6 months after treatment);
●
Vasectomized subject or partner(s); vasectomy (males);
●
Intrauterine device (females)
●
Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal 
ring with spermicidal jellies or creams; both males and females)
●
Hormonal contraceptives (oral, parenteral or transdermal) for at least 90 days 
prior to study drug administration (females).  If hormonal contraceptives are 
used, the subject and her partner should also use a single barrier method.
9.
Subject must voluntarily sign and date an informed consent, approved by an 
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to 
the initiation of and Screening for study-specific procedures.


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Rationale for Inclusion Criteria
1 – 7
To select the appropriate subject population with sufficient disease severity for 
evaluation
8
The impact of veliparib plus paclitaxel/carboplatin-based chemoradiotherapy 
followed by paclitaxel/carboplatin consolidation on the unborn fetus is 
unknown; therefore, these criteria ensure that adequate precautions are taken 
to avoid pregnancy
9
In accordance with harmonized Good Clinical Practice (GCP)
5.2.2
Exclusion Criteria
1.
Subject with prior chemotherapy or radiotherapy for current NSCLC.  Subjects 
curatively treated for past early stage NSCLC greater than 3 years ago may be 
included;
2.
Subject with prior exposure to PARP inhibitors;
3.
Subjects with known hypersensitivity to carboplatin, paclitaxel, or formulations 
containing polyethoxylated castor oil (Cremophor);
4.
Subject with prior mediastinal or thoracic radiotherapy.  Prior tangential RT to 
prior breast cancer is acceptable;
5.
Subject with major surgery in the 4 weeks prior to randomization (VATS and/or 
mediastinoscopy is not considered major surgery);
6.
Subject with a previous or concurrent malignancy except for  treated basal cell or 
squamous cell skin cancer, in situ cervical cancer, or other cancer for which the 
patient received potentially curative treatment and  has been disease-free for 
3 years or is considered cured by the investigator if has been disease-free for less 
than 3 years;
7.
Any medical condition, which in the opinion of the study investigator, places the 
subject at an unacceptably high risk for toxicities, or any subject circumstance that 
prohibits trial participation according to local law;


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8.
Subject is pregnant or lactating;
9.
Subject with sensory peripheral neuropathy of ≥ Grade 2 at baseline;
10.
Subject is unable to swallow medication;
11.
Subjects with prior history of seizure within the prior 12 months.
Rationale for Exclusion Criteria
1 – 11
For the safety of the subjects
5.2.3
Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) that the subject is receiving at the time of enrollment, 
or receives during the study, must be recorded along with the reason for use, date(s) of 
administration including start and end dates, and dosage information including dose, route 
and frequency.
The AbbVie study designated physician should be contacted if there are any questions 
regarding concomitant or prior therapy(ies).
5.2.3.1
Prior Therapy
Subjects who have received anti-cancer therapy for NSCLC prior to entry into the study 
are not eligible.  For the purposes of this protocol, prior anti-cancer therapy for NSCLC is 
defined as anti-cancer agents (e.g., cytotoxic chemotherapy, immunotherapy, biologic 
therapy, and herbal anti-cancer medicine), radiotherapy and investigational agents.  An 
investigational agent is any drug or therapy not currently approved for use in humans.


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5.2.3.2
Concomitant Therapy
The locally approved product label or applicable Summary of Product Characteristics 
(SmPC) for carboplatin and paclitaxel should be referenced for any concomitant therapy 
guidelines.
Premedication:
To reduce the severity of hypersensitivity reactions due to 
treatment with paclitaxel, manage according to 
institutional guidelines, the locally approved product label, 
local practice, or applicable SmPC (i.e., premedication 
with corticosteroids, diphenhydramine, and H2 
antagonists).
Anti-Cancer Agents:
No anti-cancer agents or investigational agents may be 
taken concurrently with veliparib.  The locally approved 
carboplatin and paclitaxel product labels or SmPCs should 
be referenced to determine if there are any 
contraindications associated with concomitant medications 
(e.g., yellow fever vaccine, phenytoin, etc.).  Hormonal 
contraceptives, hormonal replacement therapy, etc. are 
allowed.


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Supportive Care:  
Best supportive care and treatment will be given as 
appropriate to each subject (antiemetics, antibiotics, 
transfusions, nutritional support, palliative treatment for 
pain, etc.) according to institutional guidelines, NCCN 
guidelines3 or ASCO guidelines.22  For anti-emetic 
therapy, ASCO guidelines recommend for consolidation 
chemotherapy a two drug combination of palonosetron 
and dexamethasone.  If palonosetron is not available, any 
of the first generation 5-HT3 receptor antagonists may be 
used, preferably ondansetron or granisetron.
ASCO dosing guidelines are as follows:  
Palonosetron:  0.25 g IV OR 0.50 mg oral, Day 1 only 
Dexamethasone:  8 mg (IV or oral), Days 1 to 3
Aprepitant is not recommended, though clinicians may 
consider its use.  If clinicians opt to use aprepitant, dosing 
guidelines are as follows:  
Aprepitant:  125 mg Day 1, 80 mg Days 2 and 3
5-HT3 receptor antagonist dosing
Dexamethasone:  12 mg on Day 1 only
Growth Factors:
Biologic response modifiers administered for 
erythropoiesis (e.g., erythropoietin, darbepoetin alpha) 
may be administered during consolidation chemotherapy, 
but are not permitted during chemoradiotherapy.  
Granulocyte growth factors (e.g., G-CSF, GM-CSF, etc.) 
are to be administered according to the Investigator's 
standard practice and/or ASCO guidelines.  Growth 
factors may be given with the intent to prevent dose 
reductions or delays.
Surgery:
If the subject requires surgery during the study, the 
AbbVie medical monitor must be contacted.
Alternative Therapy:
No herbal remedies or non-prescription anti-cancer 
supplements may be taken for cancer treatment 
concurrently with veliparib.


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Therapies to Take 
Caution with when 
Administered with 
Paclitaxel or 
Carboplatin:
Caution should be taken when administering paclitaxel 
with known substrates (e.g., midazolam, buspirone, 
felodipine, lovastatin, eletriptan, sildenafil, simvastatin, 
and triazolam), inhibitors (e.g., atazanavir, clarithromycin, 
indinavir, itraconazole, ketoconazole, nefazodone, 
nelfinavir, ritonavir, saquinavir, and telithromycin), and 
inducers (e.g., rifampicin and carbamazepine) of CYP3A4 
or known substrates (e.g., repaglinide and rosiglitazone), 
inhibitors (e.g., gemfibrozil), and inducers 
(e.g., rifampicin) of CYP2C8.  Caution should also be 
taken when administering carboplatin with 
aminoglycosides and diuretics.  Recommendations per the 
local label should be observed.
5.3
Efficacy Pharmacokinetic, Pharmacodynamic, 
Pharmacogenetic and Safety Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
A schedule of study activities is presented in Table 2.  Pharmacodynamic (PD) and 
Pharmacogenetic (PG) assessments will be performed as summarized in Table 3.  
Pharmacokinetic (PK) assessments will be performed as summarized in Table 4 and 
Table 5.


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Table 2.
Study Activities (Phase 1 and 2)
Activity 
Screeninga
Concurrent 
(Chemoradiotherapy)
Post CRT Visitc
Consolidationd
Post-Treatment 
Visite
Final Visitf
30-Day FU Visitg
Survival Period
Wk 
1
Day 
–3
Wk
1 – 3 
Day 
1
Wk 
4 
Day 
–3
Wk 
4 – 9b
Day 
1
Wk 
7 
Day
–3b
Cycle
1
Day –2
Cycle 
1 
Day 1
Cycle 
2 
Day 1
Informed Consenth,i
X
Medical and Oncology 
History
X
PET Scanj
X
MRI of Brainj,k
X
Physical Exam 
(including weight)
Xl
Xl
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
12-Lead ECG
X
Xn
X
PFTm
X
X
Performance Status 
(ECOG)
X
X
X
X
X
X
X
X
Documentation of Non 
Childbearing Status or 
Pregnancy Test
X
Xo
Chemistry/Hematologyp
X
X
X
X
X
X
X
X
Urinalysisp
X
X
aPTT, INR
X
Tumor Assessment 
(CT Scan)q,r
Xq
Xq,r
Xq,r
Xr
QoL Questionnairess,t
X
X
X
X
Adverse 
Event/Concomitant 
Medication Assessment
X
X
X
X
X
X
X
X
X
X
Xu
X
X
Randomizations
X
Dispense 
Veliparib/placebov
X
X
X
X
X
Administer Veliparib/ 
placebov
Xw
Xw
Xw
Xx
Xx
Administer Paclitaxel/ 
Carboplatin
X
X
X
X


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Table 2.
Study Activities (Phase 1 and 2) (Continued)
Activity 
Screeninga
Concurrent 
(Chemoradiotherapy)
Post CRT Visitc
Consolidationd
Post-Treatment 
Visite
Final Visitf
30-Day FU Visitg
Survival Period
Wk 
1
Day 
–3
Wk
1 – 3 
Day 
1
Wk 
4 
Day 
–3
Wk 
4 – 9b
Day 
1
Wk 
7 
Day
–3b
Cycle
1
Day –2
Cycle 
1 
Day 1
Cycle 
2 
Day 1
Administer 
Radiotherapy
Xy
Xy
Survival Assessmentz
X
X
a.
The Screening Visit must be performed within 28 days of Week 1 Day –3 and is considered baseline.
b.
Week 7 – 9 if necessary due to radiotherapy continuing > 6 weeks.
c.
Post CRT visit can be 1 – 3 weeks after completing CRT.
d.
Subjects who discontinue therapy prior to Week 12, should have an unscheduled visit at Week 12 and at Week 18 
to assess AE, physical exam, vital signs and ECOG performance status.  Subjects who discontinue therapy after 
Week 12 and prior to Week 18, should have an unscheduled visit at Week 18 with the same assessments as above.
e.
Begin post-treatment follow-up at Week 24.  Continue every 8 weeks until 1 year after randomization, then every 
12 weeks.
f.
The Final Visit will be defined as the visit at which disease progression is identified or at the time at which the 
Investigator determines that the subject should discontinue the study or the subject discontinues for other reasons 
(i.e., withdraw consent, etc.).
g.
A 30-day Follow-Up Visit is required if the Final Visit is < 30 days from the last administration of drug.
h.
Study consent must be performed prior to initiation of any screening or study-specific procedures.
i.
Pharmacogenomic sample:  If the sample is not collected at Week 1 Day –3, it may be collected at any time 
throughout the study after the sub-study consent is signed.
j.
A PET scan and Brain MRI are required for staging, following diagnosis.
k.
MRI with contrast is required to rule out brain metastases.  CT with contrast may be performed instead if subject is 
unable to undergo MRI scanning.
l.
Physical exam not required, if done within 7 days prior to Week 1 Day –3.  Height only measured at Screening.
m.
A Pulmonary Function Test does not need to be repeated at screening, if one was performed within 12 weeks prior 
to Week 1 Day –3.  PFT will be performed at 12 months post start of radiation therapy.  If subject is no longer 
coming in for Post-Treatment Visits, every effort should be made to still collect the PFT at this 12 month 
timepoint.
n.
12-Lead ECG only at first post-treatment visit.
o.
Serum pregnancy test will be done at Screening.  Urine pregnancy test will be done prior to dosing at Week 1 
Day –3 unless the serum pregnancy test was collected within 7 days of Week 1 Day –3.
p.
Study samples for central laboratory analysis may be performed within 72 hours of the scheduled day.  A certified 
local laboratory may be used to perform laboratory analyses for treatment decisions.  Blood Draw (hemoglobin 
only) to be collected in the Post Treatment visit at 12 months post start of radiation therapy.


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Table 2.
Study Activities (Phase 1 and 2) (Continued)
q.
Baseline tumor assessments must be conducted within 28 days of Week 1 Day –3.  Post-baseline tumor assessment 
will be conducted prior to consolidation chemotherapy, at 24 weeks after start of treatment, and every 8 weeks 
(±7 days) until 1 year after beginning of treatment, and then every 12 weeks (± 7 days).
r.
Tumor assessment is to be performed at the Final Visit for subjects who discontinue the study for reasons other 
than radiographic progression and if no assessment has been performed within the last 4 weeks.
s.
For subjects in the Phase 2 portion only.
t.
Questionnaires for the assessment of quality of life will be collected at screening, post concurrent 
chemoradiotherapy, at 24 weeks after start of treatment, every 8 weeks until 1 year on study and at the final visit 
for Phase 2 portion.
u.
AE assessment only at first post-treatment visit.
v.
Veliparib in phase 1 and veliparib/placebo in Phase 2.
w.
Veliparib is to be dosed continuously until 1 day following the last day of CRT.
x.
Veliparib is to be dosed continuously for 7 days (Day –2 – Day 5) in each consolidation cycle.  It is recommended 
the site contact the subject on consolidation Cycle 1/Cycle 2 Day 5 to instruct subject about ceasing dosing.
y.
Radiotherapy is given 5 of 7 days of each week during the CRT.
z.
Following progression, survival assessments performed every 8 weeks.
Note:
Subjects who complete protocol therapy or who discontinue treatment prior to reaching an event of disease 
progression are to continue visits and radiographic assessments until progression as per RECIST version 1.1 
criteria (Appendix E).


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Table 3.
Schedule of Pharmacogenetic and Pharmacodynamic Assessments
Procedure
Visit Schedule
Before Drug 
Administration
After Drug 
Administration
Sampling Plan
Specimen Matrix
PG Blood Sampling 
Genetic (DNA)*,a
(optional)
Chemoradiotherapy: 
Week 1 Day –3 Visit
N/A
N/A
Whole Blood
Frozen –20°C or 
colder
Plasma Markers 
Chemoradiotherapy:
Week 1 Day –3,
Week 4 Day –3, 
Post CRT
and Final Visitb
Prior to dose
N/A
Blood →Plasma
Frozen –70°C or 
colder
Serum Markers
Chemoradiotherapy:
Week 1 Day –3, 
Post CRT and Final 
Visitb
Prior to dose
N/A
Blood →Serum
Frozen –70°C or 
colder
Archived Tissue 
Sample Collection
Screening
N/A
N/A
FFPEc
*
(Optional) only to be collected after additional informed consent is obtained.
a.
Every effort should be made to obtain sample at Week 1 Day –3, however sample may be collected at any point 
(with consent).
b.
The Final Visit will be defined as the visit at which the Investigator determines that the subject should discontinue 
the study or the subject discontinues for other reasons (i.e., withdraw consent, etc.).
c.
Formalin fixed, paraffin embedded (FFPE) – Sample collection should be prior to treatment start.  Subjects must 
consent to provide available archival tissue for analysis.  It is preferred to send FFPE blocks, however slides 
prepared by the local pathology laboratory are acceptable and should be prepared as described in the study specific 
laboratory manual.  If there is not enough tissue to provide the number of slides specified in the laboratory manual, 
sites should provide as many slides as possible with the available tissue.
Table 4.
Pharmacokinetic Assessments (Phase 1)
Procedure
Visit Schedule
Before Drug 
Administration
After Drug 
Administration 
(hours)
Sampling Plan
Specimen 
Matrix
PK Blood Sampling 
for Veliparib 
(ABT-888)
Chemoradiotherapy: 
Week 4 Day –3
Pre-dose
1, 2, 3, 6
Blood →Plasma
Frozen –20°C or 
colder
The date and time of the morning dose of veliparib on PK sampling day will be recorded.
The date and time of the two doses of veliparib prior to PK sampling on Week 4 Day –3 will be recorded.


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Table 5.
Schedule of Pharmacokinetic Assessments (Phase 2)
Procedure
Visit Schedule
Before Drug 
Administration
After Drug 
Administration 
(hours)
Sampling Plan
Specimen Matrix
PK Blood 
Sampling for 
Veliparib 
(ABT-888)
Chemoradiotherapy: 
Week 4 Day –3
Pre-dose
1, 2, 3
Blood →Plasma
Frozen –20°C or 
colder
PK Blood 
Sampling for 
Veliparib 
(ABT-888)
Consolidation
C1D1, C2D1
Pre-dose
--
Blood →Plasma
Frozen –20°C or 
colder
The date and time of the morning dose of veliparib on PK sampling day will be recorded. 
In Phase 2 Chemoradiotherapy portion, the date and time of the two doses of veliparib prior to PK sampling on Week 4 
Day –3 will be recorded. 
In Phase 2 Consolidation portion, the date and time of the two doses of veliparib prior to PK sampling on C1D1 and 
C2D1 will be recorded.
5.3.1.1
Study Procedures
The study procedures outlined in Table 2 are discussed in detail in this section, with the 
exception of dispensing dosing cards (Section 5.5.1.1), treatments administered 
(Section 5.5), timing of dosing (Section 5.5.4), monitoring of treatment compliance 
(Section 5.5.6), and adverse events (Section 6.0).  All study data will be recorded on 
electronic case report forms (eCRFs), with supporting source documentation.  Screening 
procedures must be performed within 28 days prior to chemoradiotherapy Week 1 
Day –3.  For procedures performed at Screening then repeated on Week 1 Day –3 prior to 
dosing, the later procedure(s) will serve as baseline for clinical assessment.  Subsequent 
study procedures should be performed within 4 days surrounding the scheduled visit date.  
Clinical laboratory tests can be performed up to 72 hours prior to dosing.
Informed Consent
Signed informed consent will be obtained from the subject before any study procedures 
are undertaken or before any prohibited medications are withheld from the subject in 
order to participate in this study.  A separate optional informed consent will be required 


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for pharmacogenetic testing.  Archived tissue collection is optional for all subjects 
participating in Cohort 1 – 5.  Subjects participating in Cohort 6 must consent to provide 
archived tissue or cytology sample for analysis.
Subjects will be considered screen failures if the informed consent has been signed and a 
study-specific procedure has been performed (e.g., central laboratories drawn), but subject 
does not randomize into the study.  The reason for screen failure will be documented in 
the source and will be captured in the eCRF.
Medical and Oncology History
The medical history includes complete medical history, including documentation of any 
clinically significant medical condition; history of tobacco and alcohol use; presence and 
severity of any symptoms/conditions associated with NSCLC; and detailed NSCLC 
oncology history (histology, TNM staging, date of diagnosis).
On chemoradiotherapy Week 1 Day –3 any changes observed from the screening 
assessments, prior to dosing, will be recorded in the subject's medical history.  At each 
subsequent visit, the subject's medical history will be reviewed and any clinically 
significant changes from baseline will be recorded in the source documents and on the 
adverse event eCRF.
PET Scan/Brain MRI 
To evaluate eligibility, a full body PET Scan must be performed to assess the subject for 
distant metastases, and a MRI of the brain must be performed to assess the subject for 
brain metastases.
Physical Examination
A physical examination, including body weight, will be performed per Table 2.  Clinically 
significant changes from baseline will be documented in the source documentation and 
eCRFs as adverse events.  Height will be measured at the Screening Visit only.  For 
height and weight assessments, the subject should not wear shoes.  Physical exam will 


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include neurological (sensory, motor, cranial nerves), head and neck, lymphatic, cardiac, 
pulmonary, hepatobiliary, gastrointestinal, genitourinary, and skin evaluation per local 
standard of care and in line with local label requirements.
Vital Signs
Vital signs will be performed per Table 2.  Vital sign determinations include sitting blood 
pressure, heart rate and body temperature.  If possible, blood pressure and heart rate 
measurements should not immediately follow scheduled blood collections.
12-Lead Electrocardiogram (ECG)
A resting 12-lead ECG will be performed per Table 2.  A qualified physician will 
determine whether any findings outside of normal physiological variation are clinically 
significant (in consultation with a cardiologist if necessary). The physician will document 
whether findings are clinically significant (CS) or not clinically significant (NCS) on the 
tracing and sign and date the tracing.  The original annotated ECG tracing along with a 
photocopy of the tracing containing the physician's assessment will be retained in the 
subject's records at the study site.
Pulmonary Function Test procedure (PFT)
The PFT procedure will be performed per Table 2.  The Pulmonary function test should 
include spirometry with FEV1 and DLCO documentation.  Hemoglobin lab assessment 
will be needed to generate a DLCO (Hb).
ECOG Performance Status
The ECOG performance status will be assessed per Table 2 as follows:


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Grade
ECOG
0
Fully Active, able to carry on all pre-disease performance without 
restriction.
1
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, e.g., light housework, office work.
2
Ambulatory and capable of all self-care but unable to carry out any work 
activities.  Up and about more than 50% of waking hours.
3
Capable of only limited self-care, confined to bed or chair more than 50% 
of waking hours.
4
Completely disabled.  Cannot carry on any self-care.  Totally confined to 
bed or chair.
Documentation of Non-Childbearing Status or Pregnancy Test
For each female subject, the Investigator will document non-childbearing status 
(surgically sterile or postmenopausal for at least 1 year) or potential childbearing status.  
Subjects with non-childbearing status do not require pregnancy tests.  For subjects of 
childbearing potential, a serum pregnancy test will be performed at Screening and the 
results must be available prior to the administration of the first dose of study drug on 
Day –3.  A urine pregnancy test should also be performed prior to dosing on Day –3 if 
> 7 days since obtaining Screening serum test results.  The test results must be reviewed 
and determined to be negative prior to dosing.  A positive urine pregnancy test will be 
confirmed with a serum pregnancy test.  Pregnancy tests may also be repeated at the 
discretion of the Investigator at any time during the study.
Should a female study subject become pregnant or suspect she is pregnant while 
participating in this study, she should inform the treating Investigator immediately 
(Section 6.7).
Clinical Laboratory Tests
Samples for chemistry, hematology and urinalysis will be collected per Table 2.  Specific 
laboratory assessments are outlined in Table 6.


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A certified local laboratory may be used to perform laboratory analyses for treatment 
decisions.  All study samples indicated in Table 2 are to be shipped to the central 
laboratory, and central laboratory results will be used for data analysis.  The central 
laboratory will provide instructions regarding the collection, processing and shipping of 
samples.
Qualified medical staff at the site will review, initial and date all local and central 
laboratory results.  Any laboratory value outside the reference range that is considered 
clinically significant by the Investigator will be followed as appropriate.  Clinically 
significant laboratory values will be recorded as adverse events if they meet the criteria as 
specified in Section 6.0.
Table 6.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Urinalysis
Hematocrit
Hemoglobin
Red blood cell (RBC) count
White blood cell (WBC) count
Neutrophils 
Bands (if indicated)
Lymphocytes
Monocytes
Basophils (if indicated)
Eosinophils (if indicated) 
Platelet count (estimate not 
acceptable)
Blood urea nitrogen (BUN)
Serum creatinine
Total bilirubin
Serum glutamic-pyruvic 
transaminase (SGPT/ALT)
Serum glutamic-oxaloacetic 
transaminase (SGOT/AST)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphorus
Uric acid
Cholesterol
Total protein
Glucose
Triglycerides
Albumin
Lactate dehydrogenase (LDH)
Magnesium
Chloride
Bicarbonate/CO2
Specific gravity
Ketones
pH
Protein
Blood
Glucose
Urobilinogen
Bilirubin
Serum Pregnancy Test
Human Chorionic Gonadotropin 
(hCG)**
Coagulation
Activated Partial
Thromboplastin Time 
(aPTT)* 
International Normalized Ratio 
(INR)*
*
Collected at Screening only.
**
At Screening and at any time point in which pregnancy is suspected or following a positive urine pregnancy test.


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Tumor Assessments (Radiologic)
A CT scan of the full chest and abdomen (with image of liver and adrenal glands) must be 
performed during screening to assess locoregional disease.  If the subject is unable to 
undergo a CT scan with IV contrast due to allergy or renal insufficiency, a non-contrast 
CT may be performed.  Magnetic resonance imaging (MRI) may be conducted in cases 
where local laws/requirements mandate, but should have Sponsor approval prior to 
performing the MRI.
Post-baseline tumor assessments will be conducted per Table 2 using RECIST version 1.1 
in the evaluation of tumor responses, as appropriate.  Tumor assessment is to be 
performed at the Final Visit for subjects who discontinue the study for reasons other than 
radiographic progression and if no assessment has been performed within the last 
4 weeks.
Quality of Life Assessment
To assess the subject's health-related quality of life and symptoms, the EORTC QLQ 
C15-PAL and the companion symptom module EORTC QLQ-LC13 will be administered 
(Phase 2 only).  All subjects in Phase 2 portion of the study must complete this 
questionnaire on paper forms, which is then entered into EDC by the Investigator or 
designee.  The Investigator or a designee will need to check the form returned by the 
subject for completeness before the subject leaves the clinic.
The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC QLQ-C30 
and consists of a global health status/QoL scale, two functional scales (physical 
functioning and emotional functioning), and seven symptom scales/items (fatigue, nausea 
and vomiting, pain, dyspnea, insomnia, appetite loss, constipation).
The EORTC QLQ-LC13 is a 13-item instrument meant for assessment of patients with 
lung cancer of various stages.  It was created according to the EORTC guidelines and is 
designed to be used in conjunction with a "core" measure such as the QLQC15-Pal.  
Along with functional scales assessed by the core instrument, the QLQ-LC13 allows for 


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assessment of dyspnea (through a three-item scale) and pain (three total:  chest, 
arm/shoulder, other), coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia 
and hemoptysis, via single-item scales.  All scores are rated in reference to the past week 
on a scale of 1 "not at all" to 4 "very much" and are converted to a 0 – 100 scale, with 
higher scores representing greater severity for symptom scales or better functioning in 
functional scales.
Randomization and Subject Number Assignment
Subject number assignment for the Phase 1 dose escalation portion and randomization 
into the Phase 2 portion will be performed as described in Section 5.5.3 and Section 5.5.4.
Dispensing Study Drug
Study drug will be dispensed as per Section 5.5.3 and Section 5.5.4.  The Interactive 
Response Technology (IRT) will assign every bottle of study drug to be dispensed to a 
subject.  AbbVie or designee will provide specific instructions on the use of IRT.
Chemotherapy and Radiotherapy Administration
Trained site personnel will administer radiotherapy, paclitaxel, and carboplatin as per 
Table 2.  Subjects will be supervised during treatment.
Survival Assessment
Survival information (the date and cause of death or last known alive date if not deceased; 
including post-treatment cancer therapy) will be collected per Table 2.  If the subject 
withdraws from study follow-up, the study staff may use a public information source 
(such as county records) to obtain information about survival status only, as appropriate 
per local regulations.
5.3.1.2
Blood Samples for Pharmacogenetic Analysis
One 4 mL whole blood sample for DNA isolation will be collected per Table 3 from each
subject who consents to provide samples for pharmacogenetic analysis.  The procedure for 


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obtaining and documenting informed consent is discussed in Section 9.3.  If the sample is 
not collected at Chemoradiotherapy Week 1 Day –3, it may be collected at any time 
throughout the study (with consent).
The sample collection tubes will minimally be labeled with "PG-DNA," protocol number, 
and subject number.  Samples will be shipped frozen to AbbVie or a designated laboratory 
for DNA extraction and long-term storage.  Instructions for the preparation and shipment 
of pharmacogenetic samples will be provided in the lab manual.
AbbVie will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.  The samples will be retained while research on veliparib (or drugs 
of this class) continues but no longer than 20 years.
5.3.1.3
Collection and Handling of Pharmacodynamic Variables
Pharmacodynamic correlative studies are exploratory in nature.  Serum, plasma and tissue 
specimens may be utilized to evaluate known and novel markers (nucleic acids, 
peptides/proteins and/or metabolites) of disease status.  PD variables will be further 
discussed in Section 5.3.7.
Blood Collection for Plasma and Serum Markers
Blood will be collected pre-dose by venipuncture at timepoints outlined in Table 3 in 
conjunction with PK samples, if possible.  The collection, processing and storage should 
be performed as described in the study-specific laboratory manual.  The complete process 
of centrifugation, transfer to cryovial and freezing should be accomplished in less than 
1 hour from the time of blood draw.  Refer to the study-specific laboratory manual for 
detailed instructions on sample collection, processing and shipment.
Archived Tissue Collection
If available, fixed samples from most recent biopsy should be collected from subjects 
participating in Cohort 1 – 5 who have consented, while subject is active on study.  While 
sending FFPE blocks is preferred, slides prepared by the local pathology laboratory are 


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acceptable and should be prepared as described in the study-specific laboratory manual.  
Subjects participating in Cohort 6 must consent to provide available archived tumor for 
analysis.  It is recognized that the availability of the samples suitable for analysis may not 
be known at the time of consent for all subjects.  Study-specific biopsies are not required 
for subject participation.
5.3.2
Drug Concentration Measurements
5.3.2.1
Blood Samples for Pharmacokinetic Analysis
Veliparib Pharmacokinetic Specimen Collection
Samples will be collected per Table 4 and Table 5.  Refer to the study-specific laboratory 
manual for detailed instructions on sample collection, processing and shipment.
5.3.2.2
Measurement Methods
Plasma concentrations of veliparib will be determined using a validated method under the 
supervision of the Drug Analysis Department at AbbVie.  Additionally, veliparib 
metabolite(s) concentrations in plasma samples may be determined using a non-validated 
or a validated assay.
5.3.3
Efficacy Variables
The primary efficacy endpoint is Progression Free Survival (PFS).  The secondary 
efficacy endpoints are Overall Survival (OS), Objective Response Rate (ORR), and 
Duration of Overall Response (DOR).  The tertiary efficacy endpoints are Quality of Life 
and ECOG performance status.
5.3.4
Safety Variables
AbbVie will assess adverse events, laboratory data, ECGs and vital signs during the study.  
Adverse events will be assessed according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events NCI CTCAE version 4.0.23  During the conduct 
of the study, the AbbVie medical and safety team will be monitoring subject laboratory 


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results and serious adverse event data as it is reported.  AbbVie will review blinded 
aggregate safety data on a regular basis and may enlist the assistance of the DMC at any 
time to evaluate any trends in the safety data that are identified.
5.3.5
Pharmacokinetic Variables
For Phase 1 portion, values for the pharmacokinetic parameters of veliparib and its 
possible metabolite(s), including the maximum observed plasma concentration (Cmax), the 
time to Cmax (peak time, Tmax), and the area under the plasma concentration-time curve 
(AUC) will be determined using non-compartmental methods.
In addition, a nonlinear mixed effect modeling (NONMEM) analysis may be conducted 
using veliparib concentration data collected in both Phase 1 and Phase 2 portions to 
estimate the population pharmacokinetic parameters of veliparib, including apparent oral 
clearance (CL/F) and volume of distribution (V/F).  Results of the NONMEM analysis 
may be reported in a separate pharmacokinetic report.
Additional parameters may be estimated if useful in the interpretation of the data.
AbbVie or a designated laboratory will store the pharmacokinetic samples in a secure 
storage space with adequate measures to protect confidentiality.  To increase confidence 
in trends, remaining sample aliquots may be used to perform replicate tests, or sample 
analysis at additional time points for tests currently identified in the protocol.  Upon 
completion of this research AbbVie or a designated laboratory will destroy the samples.
5.3.6
Pharmacogenetic Variables
DNA samples may be sequenced and data analyzed for genetic factors contributing to the 
disease or to the subject's response to veliparib (or other study treatment) in terms of 
pharmacokinetics, efficacy, tolerability, and safety.  Such genetic factors may include 
genes for drug metabolizing enzymes, drug transport proteins, genes within the target 
pathway, genes believed to be related to the disease or to drug response.  Some genes 
currently insufficiently characterized or unknown may be understood to be important at 


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the time of analysis.  The samples may be analyzed as part of a multi-study assessment of 
genetic factors involved in the response to veliparib, drugs of this class, or the disease 
state.  The samples may also be used for the development of diagnostic tests related to 
veliparib, drugs of this class, or the disease state.  The results of pharmacogenetic analyses 
may not be reported with the study summary.
5.3.7
Pharmacodynamic Variables
Several putative biomarkers of efficacy and response may be evaluated in this protocol 
with the goal of exploring the relationship between tumor response and/or disease status.
Biospecimens collected may be evaluated for genetic lesions whether they occur by 
amplification, chromosomal loss and/or mutational/methylation with the intent of 
identifying potential associations with subject outcome or to better characterize the 
disease.  These characterizations may be included, but are not limited, characterization of 
gene expression, methylation/mutational status or copy number changes of genes, 
particularly those involved in DNA repair pathways.  Additional analysis aimed at 
identifying underlying defects in the homologous recombination pathway, regardless of 
etiology, may be performed and associated with response.
Biospecimens may be evaluated for levels of biomarkers including nucleic acids, 
proteins/peptides and metabolites.  For example, protein analysis of relevant proteins, 
including but not limited to, DNA repair proteins, such as ERCC1 and XPF, may be 
performed on tumor tissue obtained from each consented subject.
Samples collected during the course of this study may be used to investigate new 
scientific questions related to this study.  Additionally, the samples may be anonymized 
and used for diagnostic test development.  AbbVie (or a designated laboratory) will store 
the samples in a secure storage space with adequate measures to protect confidentiality.  
The samples will be retained while research on veliparib (or drugs of this class) continues 
for up to but no longer than 20 years. 


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5.4
Removal of Subjects from Therapy or Assessment
Each subject has the right to withdraw from study treatment at any time.  In addition, the 
Investigator may discontinue a subject from the study treatment at any time for any reason 
if the Investigator considers it necessary, including the occurrence of an adverse event or 
noncompliance with the protocol.  Each subject will be withdrawn from the study or study 
treatment (as applicable) per Section 5.4.1 if any of the following occur:
●
The subject has radiographic progression according to RECIST version 1.1.
●
The subject requires alternate anti-cancer agents during the study period.
●
The subject experiences unacceptable treatment toxicity or the Investigator 
believes it is otherwise in the best interest of the subject.
●
Subject is suspected to be pregnant; pregnancy is confirmed or begins 
breastfeeding during the treatment portion of the study.
●
The subject or subject's legally acceptable representative decides to withdraw 
consent for any reason.
●
Any other medical reason that AbbVie or the study Investigator deems 
appropriate.
5.4.1
Discontinuation of Individual Subjects
Subjects who discontinue treatment with veliparib/placebo + paclitaxel/carboplatin prior 
to reaching an event of disease progression are to continue assessments until disease 
progression.  Refer to Section 5.4.1.1 for more details.
When subject discontinuation from the study (without reaching a protocol-defined 
endpoint) is planned, the Investigator is to notify the AbbVie medical monitor or the 
clinical team representative (Section 7.0) via telephone as soon as possible (provided, in 
each case, subject care and safety are not compromised).  If not notified prior to 
discontinuation, the AbbVie medical monitor may contact the site to discuss the reason 
for withdrawal from the study.


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The visit at which the subject discontinues the study will be considered the final visit.  At 
the Final Visit, the reason(s) for the discontinuation from the study will be recorded and 
assessments will be performed per Table 2.  For the randomized portion of the study, the 
investigator must report the withdrawal in the IRT system within three days of the 
subject's discontinuation visit.
Subjects who have a Final Visit within 30 days of therapy will have one Follow-Up Visit 
approximately 30 days after the Final Visit.  If a subject is discontinued from the study 
with an ongoing adverse event or an unresolved clinically significant laboratory result, the 
site will attempt to provide follow-up until a satisfactory clinical resolution of the 
laboratory results or adverse event is achieved.
In the event that a positive result is obtained on a pregnancy test for a subject during the 
study, the administration of study drug to that subject must be discontinued immediately.  
The site must report the positive pregnancy test result by telephone within 24 hours to 
one of the AbbVie representatives listed in Section 6.6.
5.4.1.1
Discontinuation of Veliparib/Placebo and 
Paclitaxel/Carboplatin
Subjects will receive veliparib/placebo, thoracic radiotherapy, paclitaxel and carboplatin 
per Table 2 or until reaching a protocol defined event of disease progression or 
experiencing unmanageable toxicity.  Dose reductions of carboplatin and paclitaxel will 
occur on the basis of the toxicity observed and may result in discontinuation of either 
agent.  The subject may continue veliparib/placebo while any other component of therapy 
is ongoing.  If toxicities have resulted in discontinuation of radiotherapy and paclitaxel 
and carboplatin, veliparib/placebo will also be discontinued.  At the Investigator's 
discretion, radiotherapy or paclitaxel or carboplatin administration may continue after 
veliparib/placebo has been discontinued.


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5.4.2
Discontinuation of Entire Study
AbbVie may terminate this study prematurely, either in its entirety or at any study site, for 
reasonable cause provided that written notice is submitted in advance of the intended 
termination.  The investigator may also terminate the study at his/her site for reasonable 
cause, after providing written notice to AbbVie in advance of the intended termination.  
Advance notice is not required by either party if the study is stopped due to safety 
concerns.
The following procedures for discontinuation will be followed:
●
If the Sponsor has decided to prematurely discontinue the study, the Sponsor 
will promptly notify in writing each Investigator as well as regulatory 
authorities of the decision and give detailed reasons for the discontinuation.
●
Each Investigator must promptly notify the IRB/IEC and give detailed reasons 
for the discontinuation.
●
Each Investigator must promptly notify the enrolled subjects of the premature 
discontinuation and administer appropriate treatments such as replacement of 
protocol therapy, if applicable, by other appropriate regimens.
5.5
Treatments
5.5.1
Treatments Administered
All subjects will receive the following:
Concurrent Chemoradiotherapy
Veliparib will be administered BID beginning 3 days prior to beginning 
chemoradiotherapy.  Chemotherapy will consist of Carboplatin AUC 2 mg/mL/min and 
Paclitaxel 45 mg/m2 administered intravenously on Day 1 of each week during 
radiotherapy.  Radiotherapy will be delivered using 3D conformal RT or IMRT and 
subjects will receive a total of 60 – 63 Gy.  Chemoradiotherapy may be extended up to 
9 weeks in duration due to treatment delays.  Subjects who have not completed 


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chemoradiotherapy after 9 weeks should proceed to consolidation therapy or observation 
at the discretion of the Investigator.
The first cohort of subjects in the dose escalation portion of the study will receive 
veliparib 60 mg BID during the chemoradiotherapy portion of treatment.  Additional 
cohorts of subjects will be treated at the dose levels indicated in Table 1, with cohort size 
and dose change determined according to tolerability.  AbbVie and the Phase 1 
investigator group will review available safety data through the completion of 
radiotherapy for each cohort and for all prior patient cohorts prior to making a decision to 
expand a dose level cohort, escalate to a higher dose level, or proceed to a lower dose 
level in a new cohort.  The following rules for enrollment of an additional 3 patients per 
cohort, dose escalation, and determination of the maximum tolerated dose (MTD) will be 
applied:
1.
If no subject (0/3) experiences a dose limiting toxicity (DLT), then dose escalation 
may occur.
2.
If one subject (1/3) experiences a DLT, then 3 additional subjects will be enrolled 
at the same dose level.  If none of the additional subjects (0/3) experience a DLT 
(i.e., 5/6 patients did not experience a DLT at the current dose level), then dose 
escalation may occur.  If ≥ 2/6 patients experience the same DLT at the current 
dose level, then no further patients will be enrolled in the cohort and the MTD will 
be considered to have been exceeded. 
3.
If ≥ 2 patients (≥ 2/3) experience the same DLT, then no further patients will be 
enrolled in the cohort and the MTD will be considered to have been exceeded.  If 
≥2 patients experience different DLT's, either the MTD will be considered to have 
been exceeded OR 3 additional subjects will be enrolled at the same dose level.  
Dose escalation may occur provided ≥ 2/6 patients do not experience the same 
DLT at the current dose level.  If ≥ 2/6 patients experience the same DLT, the 
MTD will be considered to have been exceeded.


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Consolidation Chemotherapy
No more than 8 weeks after completion of concurrent chemoradiotherapy, 
veliparib/placebo 120 mg or 240 mg BID will be administered beginning 2 days prior to 
the start of paclitaxel/carboplatin infusion and will continue through Day 5 of each 21-day 
cycle.  Carboplatin AUC 6 mg/mL/min and Paclitaxel 200 mg/m2 will be administered 
intravenously on Day 1 of each 21-day cycle.  Subjects will receive a maximum of 
2 cycles of consolidation chemotherapy.  Subjects who require > 8 weeks to recover from 
toxicities resulting from chemoradiotherapy should not receive consolidation.
Phase 2 Treatment Regimen:  RPTD or Placebo
AbbVie will review available safety data from all subjects in the dose escalation portion 
of the study and determine the CRT and consolidation RPTDs.  Subjects in the 
randomized portion of the study will receive the veliparib RPTD or placebo during CRT 
and consolidation.
5.5.1.1
Administration of Veliparib/Placebo (All Subjects)
Subjects will self-administer the morning dose of veliparib/placebo and the evening doses 
of veliparib/placebo approximately 12 hours apart with or without food in the same 
calendar day.
It is recommended that if a subject misses a scheduled dose of veliparib/placebo and less 
than 6 hours have passed since the scheduled dosing time, the dose should be immediately 
taken.  It is recommended that if more than 6 hours have passed since the scheduled 
dosing time, the subject should not take the missed dose but should wait for the next 
regularly scheduled dose.
If the subject vomits within 15 minutes of taking veliparib/placebo, another dose is to be 
taken.  The dose may only be repeated once.  If more than 15 minutes has passed from the 
time of oral dosing then no additional doses will be taken.  The subject is to contact the 
Investigator if additional veliparib/placebo is needed to complete BID dosing through 
Day 5 of the cycle. 


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Subjects will be provided self-administration instructions and subject dosing cards to 
record the date and time the veliparib/placebo was administered.  Subjects will be 
instructed to store veliparib/placebo according to specific directions included in 
Section 5.5.2.3.  Subjects should return bottles of veliparib/placebo (empty, partially filled 
or full) to the study site as indicated in Section 5.5.7. 
5.5.1.2
Administration of Paclitaxel, and Carboplatin (All Subjects)
Paclitaxel and Carboplatin During Concurrent Chemoradiotherapy
Carboplatin and paclitaxel will be administered intravenously, on Day 1 of every week 
during radiotherapy.  Paclitaxel will be infused prior to carboplatin.  Investigators should 
evaluate subjects for carboplatin and paclitaxel treatment per the locally approved product 
label,1,2 local practice, or applicable SmPC.  Paclitaxel will be administered intravenously 
over approximately 60 minutes at a dose of 45 mg/m2.  Carboplatin will be administered 
intravenously over approximately 30 minutes (at AUC 2 mg/mL/min) immediately 
following paclitaxel infusion.
Consolidation Chemotherapy
Consolidation chemotherapy will begin no more than 8 weeks following RT.  Subjects 
who require > 8 weeks to recover from toxicities resulting from chemoradiotherapy 
should not receive consolidation.  
Carboplatin and paclitaxel will be administered intravenously on Day 1 of every 21-day 
cycle.  Paclitaxel will be infused prior to carboplatin.  Investigators should evaluate 
subjects for carboplatin and paclitaxel treatment per the locally approved product 
label,24,25 local practice, or applicable SmPC.  Paclitaxel will be administered 
intravenously over approximately 3 hours at a dose of 200 mg/m2.  Carboplatin will be 
administered intravenously over approximately 30 minutes (at AUC 6 mg/mL/min) 
immediately following paclitaxel infusion.


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Calculation of Carboplatin Dose
Per the FDA Guidelines, the maximum dose of carboplatin (this dose should not be 
exceeded) may be calculated using the following formulas:26
Total carboplatin dose (mg) = target AUC × (GFR + 25) [Calvert formula]
Maximum carboplatin Dose (mg) = target AUC (mg/mL/min) × (150 mL/min)
●
For a target AUC = 2, the maximum dose is 2 × 150 = 300 mg
●
For a target AUC = 6, the maximum dose is 6 × 150 = 900 mg
5.5.1.3
Thoracic Radiotherapy
Thoracic radiotherapy will be administered by 3-dimensional conformal RT or intensity 
modulated radiotherapy (IMRT), including volumetric modulated arc techniques.  
Radiotherapy will be delivered in dose fractions of 1.8 – 2.0 Gy on approximately 5 of 
every 7 days (excluding weekends and holidays), with the total dose measuring 60 –
63 Gy.  Radiotherapy will be delivered in ≤9 weeks.
Radiotherapy must begin on Week 1 Day 1 of CRT.
An interruption in RT of >7 days should be discussed with the AbbVie medical monitor. 
Equipment
●
Energy: Megavoltage quality radiation will be used with a nominal energy of 
6 – 10 MV.  Proton therapy is not allowed on this protocol.
●
Geometry: The distance from the radiation source to the isocenter should not 
be less than 100 cm.
●
The use of daily image-guidance is highly encouraged.  
Planning Techniques:
All sites must provide details regarding their image guidance technique in EDC.


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Simulation:
All patients will undergo CT based treatment planning in appropriate immobilization 
devices in the supine position.  A custom immobilization cast is encouraged but not 
required.  All components of immobilization must, in conjunction with the image 
guidance being used, ensure that both interfraction set-up uncertainty and unaccounted for 
intrafraction motion be minimized.  The planning CT scan should be performed with 
IV contrast unless the patient has a known contrast allergy or renal insufficiency as 
IV contrast allows better distinction between tumor and adjacent normal tissue or 
atelectasis. 
Contiguous CT slices with ≤ 3.0 mm thickness between scans in the region of the primary 
tumor and pathologically involved lymph nodes, and no more than 5 mm thickness in the 
remaining regions starting from the level of the cricoid cartilage and extending inferiorly 
through the entire liver volume.  
Four-dimensional CT (4D-CT) is permitted and highly encouraged for the study.  There 
are many valid approaches to defining target volumes and margins using multiple datasets 
representing different phases of the breathing cycle.  These include but not limited to:
a.
Design of the PTV to include the excursion of the primary and nodes during free 
breathing (ITV approach).
b. Limited excursion during a voluntary or automatic breath hold (e.g., Elekta ABC 
device).
c.
Or a gating approach (Varian RPM system).
d. Or fiducial marker tracking.
Target Volume Definitions
The nomenclature and definitions of ICRU Reports 50 and 62,27 shall be followed in this 
study. 


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GTV Definition:
The GTV will be the volume of tumor visible on CT or PET imaging or biopsy proven 
sites (not meeting radiographic/metabolic criteria).  This will in general include lymph 
nodes within the mediastinum ≥ 1.0 cm in short axis diameter and/or PET positive lymph 
nodes (SUV max > 3).  Information from PET imaging should be used to determine occult 
nodal areas as well as to accurately contour gross disease within areas of atelectasis.  The 
volume(s) may be disjointed.
For areas within or near inflated lung tissue, lung window settings will be utilized for 
contouring.  For disease within or abutting the mediastinum, soft tissue window settings 
will be used. 
CTV Definition: 
The CTV is defined to be the GTV plus a 0.5 cm to 1 cm margin as appropriate to account 
for microscopic tumor extension.  However, the CTV should not cross natural anatomic 
barriers to tumor extension such as fissures or fascial planes unless these structures are 
directly abutted or invaded by the GTV.  Elective treatment of the mediastinum and 
supraclavicular fossae will not be done.
PTV Definition:
PTV expansion includes two components:  tumor motion and setup uncertainty.  The 
margin for set-up uncertainty will be uniform for this study at 0.5 cm and independent of 
the use of IGRT.  The margin for tumor motion will be dependent on type of assessment 
and respiratory motion management techniques used for the study and in addition to the 
0.5 cm margin for set-up uncertainty.
●
Free Breathing Treatment/Simulation Motion Margin:  Sup-Inf:  1 cm, axial 
0.5 cm
●
Breathhold/gating:  Sup-inf:  0.5 cm, axial 0.3 cm
●
Abdominal compression:  Sup-inf 0.8 cm, axial 0.5 cm
●
4DCT:  Union of CTVs for Sup-inf and axial


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Treatment Planning: 
Techniques:  3D Conformal Planning or IMRT is required in this protocol.  Both planar 
and non-coplanar field arrangements are acceptable.  Use of IMRT/VMAT planning 
requires use of 4DCT imaging for full respiratory motion assessment.
Heterogeneity corrections:  All radiation doses will be calculated with heterogeneity 
corrections to take into account the density differences within the irradiated volume.  The 
acceptable heterogeneity dose calculation methods can be found on the QARC (Quality 
Assurance Review Center) website (www.QARC.org).  Non-validated dose calculation 
algorithms (Clarkson, pencil beam) will not be allowed for this study.  
Dose Specifications:  The prescribed dose is 60 – 63 Gy in approximately 30 fractions 
(1.8 – 2.0 Gy daily).  The treatment plan will be normalized such that 95% of the PTV 
receives the prescription dose.  No more than 0.03 cc can receive more that 120% of the 
prescription dose.  The maximum and minimum doses (0.03 cc) will be reported. 
Critical Structures:  Normal tissue constraints should be prioritized in the following 
manner for treatment planning:  1 = spinal cord, 2 = Lung, 3 = esophagus, 4 = brachial 
plexus, 5 = heart.  Critical structures should be contoured based on the RTOG lung 
contouring atlas.
●
Spinal Cord:  The spinal cord is contoured based on the confines of the bony 
limits of the spinal canal.  The spinal cord dose limit is the highest priority 
dose constraint and must be adhered to above all other dose constraints.  No 
more than 0.03 cc of the spinal cord can receive > 50.5 Gy total dose.
●
Lungs:  The total lung volume is defined as the sum of the volume of both 
lungs minus the GTV.  The dose-volume constraints to the lung is considered 
the second highest priority and must be met, except if it conflicts with spinal 
cord dose constraints.  The proportion of the total lung volume that received 
20 Gy or greater (V20) must be less than 35%.  Additionally the mean lung 
dose should be less than 20 Gy. 


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●
Esophagus:  The entire esophagus from the bottom of the cricoid to the GE 
junction should be contoured.  No more than 0.03 cc may receive > 63 Gy.  
The mean dose to the esophagus should be less than 34 Gy.  The esophagus 
should not be circumferentially irradiated with > 60 Gy.  The V60 should be 
reported for each patient. 
●
Brachial Plexus:  The ipsilateral brachial plexus should be contoured for upper 
lobe tumors.  No more than 0.03 cc of the brachial plexus should receive 
> 63 Gy. 
●
Heart:  The heart and pericardium should be contoured from base to apex of 
the heart.  The following limits are recommended:  V60 < 33%, V45 < 66%, 
V40 < 100%.  Every effort should be taken to minimize the dose to the heart. 
Treatment Delivery:
All treatment will be administered 5 days per week, 1 treatment per day.  All fields must 
be treated daily.  The entire PTV must be treated daily.
Radiation Planning QA/Documentation Requirements
●
Copies of dose calculations and daily charts will be kept with source 
documents.  Sites participating in the Phase 2 portion of the trial will be 
required to submit patient treatment plans to QARC for QA.  Please refer to 
ABT-888, Study M14-360 Radiation Therapy Quality Assurance Manual for 
detailed description of RT credentialing requirements and the QA process.
Definitions of Deviations in Protocol Radiation Planning/Delivery:
●
Volume:
○
Minor Deviation:  margins for CTV and or PTV are less than specified or 
excessively large as determined by radiation study chair/quality reviewer.
○
Major Deviation:  GTV incorrectly identified resulting in < 100% dosing 
of gross disease.
●
Dose Prescription:
○
Minor:  The prescribed dose differs from that in the protocol by 6 – 10%.


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○
Major:  The prescribed dose differs from that in the protocol by more than 
10%.
●
Dose Uniformity:
○
Minor Deviation:  The protocol specified dose covers between 90 – 95% of 
the PTV or the minimum dose to 1 cc of the PTV is between 90 – 95% of 
the protocol dose or the maximum dose to 1 cc of the PTV exceeds 120% 
of the protocol dose.
○
Major Deviation:  The protocol specified dose covers less than 90% of the 
PTV or the minimum dose to 1 cc of the PTV is < 90% of the protocol 
dose or the maximum dose to 1 cc of tissue outside the PTV exceeds 120% 
of the protocol dose.
●
Critical Organ Radiation Dosing:
○
Minor:  
●
Mean Lung Dose between 20 and 24 Gy
●
The dose to the heart, esophagus, or brachial plexus exeeds limits 
specified above.
○
Major:  
●
Lung V20 > 35%, Mean Lung Dose > 24 Gy.
●
Spinal cord dose 0.03cc > 50.5 Gy.
Note:  Deviations will be assessed by QARC at the time of final review following the 
completion of radiotherapy.  Sites will receive a report to inform them of the results of the 
final review.  Please see the ABT-888, Section Study M14-360 Radiation Therapy Quality 
Assurance Manual for further information regarding the QA process.
Radiation Therapy Adverse Events:
Esophagitis:  Esophageal complaints are common with thoracic chemoradiotherapy.  
Esophagitis does not constitute a reason to interrupt combined therapy provided oral 
intake is sufficient to maintain hydration.  Patients should be advised to avoid alcoholic, 
acidic, or spicy foods.  Viscous lidocaine, sucralfate, and other medications should be 
used for symptom relief.  The following are also commonly used to manage esophagitis:


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●
Ketoconazole 200 mg PO QD or Fluconazole 100 mg PO QD daily until the 
end of radiation.
●
Proton pump inhibitor (such as omeprazole) or H2 blocker (such as Ranitidine) 
taken daily until the end of radiation.
5.5.2
Identity of Investigational Products
Information regarding the veliparib formulation to be used in this study is presented in 
Table 7.
Table 7.
Identity of Investigational Product
Study Drug
Dosage 
Form
Strength
Route of 
Administration
Manufacturer
Veliparib (ABT-888)
Capsule
20 mg and 40 mg active
Oral
AbbVie
Placebo
Capsule
20 mg and 40 mg placebo
Oral
AbbVie
5.5.2.1
Standard of Care Medicinal Products for Study Treatment
Information regarding carboplatin and paclitaxel to be used in this study is presented in 
Table 8.
Table 8.
Standard of Care Medicinal Products for Study Treatment
Study Treatment
Dosage Form
Route of Administration
Carboplatin (commercially available)*
Solution in a vial
Intravenously
Paclitaxel (commercially available)*
Solution in a vial
Intravenously
*
Carboplatin and paclitaxel formulations may vary based on the source.
Carboplatin or paclitaxel should be obtained commercially via the site pharmacy or by a 
sponsor approved vendor.
5.5.2.2
Packaging and Labeling
Veliparib will be packaged in bottles containing 5, 11, or 48 doses of veliparib or placebo.  
This will allow for the 2, 5 or 21 days of administration with at least 1 additional dose to 


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cover loss, spillage or replacement due to vomiting within 15 minutes.  Each bottle label 
will include all information as required by local regulations and must remain affixed to 
the bottle.  All blank spaces on the label will be completed by site staff prior to dispensing 
to the subject.
AbbVie will provide detailed instructions and training for the handling of study supplies 
to the study site.
5.5.2.3
Storage and Disposition of Study Drugs
Veliparib or Placebo
Table 9.
Study Drug Storage Conditions
Study Drug
Country
Storage Conditions
Veliparib or placebo
All countries, except 
Australia/New Zealand and Japan
Store at 15° to 25°C 
(59° to 77°F)
Veliparib or placebo
Australia/New Zealand
Store below 25°C
Veliparib or placebo
Japan
Store at 15° to 30°C
All clinical supplies must be stored in a secure place until they are dispensed for subject 
use, are destroyed at the site or are returned to AbbVie.
Investigational products are for investigational use only, and are to be used only within 
the context of this study.  The clinical supplies for this study must be maintained under 
adequate security and stored under conditions specified on the label.
Storage and Disposition of Carboplatin and Paclitaxel
Paclitaxel
Vials must be stored between 15°C to 25°C (59°F to 77°F) (or per locally approved label 
or SmPC) in the provided cartons to protect from light.


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Carboplatin
Vials must be stored between 15°C to 25°C (59°F to 77°F) (or per locally approved label 
or SmPC) in the provided cartons to protect from light.
5.5.3
Method of Assigning Subjects to Treatment Groups 
In the Phase 1 portion, Screening number and study drug will be assigned using the IRT 
system.  In the randomized Phase 2 portion of the study, all subjects will be randomized 
using an IRT system.  Before the study is initiated, directions for the IRT will be provided 
to each site.  The site will contact the IRT to obtain a Screening (subject) number once the 
subject has signed the informed consent and a study-specific procedure has been 
performed (i.e., central laboratory samples drawn).  Once the screening number is 
assigned, if the subject is not enrolled into the study, the reason for screen failure will be 
documented in the source document and in the eCRF.  For subjects participating in the 
Phase 2 portion, a unique randomization number will be provided through the IRT 
system.
Subjects will be permitted to re-screen for the study with permission from the AbbVie 
medical monitor.  Subjects should keep the same subject number if re-screened.
A bottle number randomization schedule and a subject randomization schedule will be 
generated by the Clinical Statistics Department at AbbVie prior to the start of the study.  
A copy of all randomization schedules will be kept by the Clinical Statistics Department 
at AbbVie and a copy will be forwarded to the IRT vendor.
Each subject will be dispensed veliparib per Table 2.  In the event of chemotherapy and/or 
RT interruption and/or if vomiting occurs and additional bottles of veliparib/placebo are 
needed, the study site personnel must contact the IRT so that additional bottles of 
veliparib may be dispensed.


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5.5.4
Selection and Timing of Dose for Each Subject
Subjects in the dose escalation portion of the study will receive a veliparib starting dose of 
60 mg and will follow the dose escalation procedures outlined in Section 5.5.1.
All Phase 2 randomized subjects will receive the RPTD of veliparib or placebo orally BID 
per Table 2.  No other doses or schedules of veliparib are being investigated in this study.  
Refer to Section 5.5.1.1, Section 5.5.1.2 and Section 5.5.1.3 for additional dosing 
information for veliparib/placebo, paclitaxel/carboplatin and RT.
5.5.5
Blinding
All subjects will be treated with open-label paclitaxel and carboplatin (Phase 1 and 
Phase 2).
Subjects in Phase 1 will be treated with open-label veliparib.  In Phase 2, AbbVie, the 
Investigator, the study site personnel and subject will remain blinded to each randomized 
subject's treatment with veliparib or placebo throughout the course of the study.
5.5.5.1
Blinding of Investigational Product
AbbVie must be notified before the blind is broken unless identification of the study drug 
is required for medical emergency, i.e., situation in which the knowledge of the specific 
blinded treatment will affect the immediate management of the subject/patient's 
conditions (e.g., antidote is available).  The IRT system will provide access to blinded 
subject treatment information in the case of medical emergency.  AbbVie must then be 
notified within 24 hours of the blind being broken.  The date and reason that the blind was 
broken must be recorded in the source documentation and eCRF, as applicable.  In the 
event the AbbVie Clinical Project Team should break the blind, the reason will be 
documented in a note to study file and on the appropriate eCRF.


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5.5.5.2
Blinding of Data for Data Monitoring Committee (DMC)
To ensure subject safety, an internal data monitoring committee will review un-blinded 
safety data when 45 subjects in the Phase 2 portion of the study have completed 
chemoradiotherapy, or reached an event of disease progression or death, or discontinued 
the study.
5.5.6
Treatment Compliance
The Investigator or his/her designated and qualified representatives will 
administer/dispense study drug only to subjects enrolled in the study in accordance with 
the protocol.  The study drug must not be used for reasons other than that described in the 
protocol.  Veliparib/placebo should be taken as directed by the Investigator.  Carboplatin 
and paclitaxel will be administered intravenously by trained site personnel.
Subjects will be instructed to return their dosing cards and all remaining veliparib/placebo 
bottles (empty, partially filled or full) to the study site personnel as follows:  
●
On Chemoradiotherapy Week 4 Day –3 and Week 7 Day –3 (CRT)
●
At the Post CRT Visit
●
At the Consolidation Cycle 2 Day 1 Visit
●
At the first Post-Treatment Visit
Subjects should be questioned regarding their adherence to the assigned treatment 
schedule at each visit.  The Investigator or his/her designated and qualified representatives 
will also confirm that the subject took the required number of capsules per protocol.
A subject will be considered compliant with study drug, veliparib, paclitaxel/carboplatin if 
80% of the assigned dose is taken during a cycle.  Compliance below 80% will require 
counseling of the subject by study site personnel.


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5.5.7
Drug Accountability
The site will record the dose of carboplatin and paclitaxel given to each subject in the 
source documents and on the eCRF.  For sites that obtain both carboplatin and paclitaxel 
without sponsor assistance, site inventory and accountability of carboplatin and paclitaxel 
will not be performed, and drug accountability forms will not be provided.  For sites that 
receive assistance in sourcing the commercial product, accountability must be done to the 
extent to manage availability and ensure all product sent has been used solely for the 
study.
Upon receipt of a shipment of veliparib/placebo, the representative at each site will 
1) open and inspect the shipment; 2) verify that the veliparib/placebo has been received 
intact, in the correct amounts and at the correct address; 3) sign and date the Proof of 
Receipt (POR) or similar documentation accompanying the shipment; 4) register the 
shipment as received via the IRT.  Study drug kits will not be available for dispensation to 
a subject until the shipment is confirmed as received in the IRT system. All study drugs 
must be retained in the designated secure area under proper storage conditions.  This will 
be documented by signing and dating the Proof of Receipt (POR) or similar document or 
via direct recording in the IRT. 
An overall accountability of the study drug will be performed and verified by the site 
monitor throughout the study and at the study site closeout visit.  An accurate running 
inventory of veliparib/placebo will be maintained utilizing the IRT drug accountability 
module and, if required, according to your institutional policy and will include the lot 
number, POR number(s), the bottle/kit numbers, and the date study drug was dispensed 
for each subject.
In the event that the IRT is not operable, the above information will be documented on 
forms provided by the Sponsor. 
The Investigator or designee will document the bottles of veliparib/placebo returned and 
the number of capsules directly in the IRT system.  If the number of capsules taken and 


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the number of capsules returned do not add up to the total number of capsules dispensed, 
an explanation is required and should be documented in the IRT.
Upon completion or termination of the study, all original bottles/kits containing unused 
veliparib/placebo (empty containers will be defaced and discarded on site) will be 
returned to AbbVie according to AbbVie's instructions, or if pre-arranged between the 
sponsor and site, destruction of used and unused bottles will be performed at the site.
The study Investigator or his/her designated representative agrees not to supply study 
medication to any persons not enrolled in the study or not named as a sub-investigator 
listed on the FDA 1572 or Investigator Information and Agreement (IIA) form.
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
Phase 1 data and preliminary Phase 2 data described in Section 3.0 suggests the addition 
of veliparib to radiotherapy or to paclitaxel/carboplatin may improve outcome of NSCLC 
patients.  The dose escalation portion of this trial will determine the safe dose of veliparib 
that can be administered with concurrent chemoradiotherapy.  The randomized, 
double-blind, placebo controlled portion of the study will evaluate the effect of veliparib 
added to paclitaxel/carboplatin and radiotherapy for treatment of Stage III NSCLC.
ESMO28 and National Comprehensive Cancer Network (NCCN) guidelines3 recommend 
chemoradiotherapy and chemotherapy for locally advanced NSCLC that is not treated by 
surgery.  Recommendations include conformal radiotherapy with sequential 
chemotherapy or concurrent + sequential chemotherapy.  Recommended platinum 
doublets for use in such regimens include carboplatin-paclitaxel, carboplatin pemetrexed, 
cisplatin-pemetrexed, cisplatin-etopeside, and cisplatin vinblastine.  Randomized 
controlled studies suggest that concurrent chemoradiotherapy followed by consolidation 
chemotherapy may be the optimal schedule for multi-modality therapy in this setting.  
Thus, the backbone regimen in this study is suitable treatment for the subjects.


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A randomized, double-blind, placebo controlled study such as described here is optimal 
for assessing the value of add-on therapy (veliparib) to a current standard treatment.
5.6.2
Appropriateness of Measurements
Standard pharmacokinetic, statistical, clinical, and laboratory procedures will be utilized 
in this study.
The efficacy measurements in this study are standard and validated.  PFS is a commonly 
used surrogate for OS in non-pivotal trials of NSCLC.  OS is a widely accepted endpoint 
of clinical importance for the evaluation of subjects with previously untreated advanced or 
metastatic NSCLC.  Response rate and duration of response may add supporting evidence 
to a finding of improved PFS and OS with veliparib combination therapy.  Additionally, 
RECIST version 1.1 is a validated guideline for the measurement of responses in subjects 
with advanced or metastatic solid tumors.29
5.6.3
Suitability of Subject Population
Subjects with pathologically documented and previously untreated Stage III NSCLC will 
be selected to participate in this study.  The proposed inclusion and exclusion criteria are 
anticipated to result in a study patient population representative of Stage III NSCLC 
patients who receive concurrent radiotherapy and consolidation chemotherapy according 
to current practice guidelines.1-3
5.6.4
Selection of Doses in the Study
The doses of standard therapy (radiotherapy, carboplatin, paclitaxel) are guideline 
recommended or based on randomized studies of subjects with advanced NSCLC.3  The 
dose escalation portion of this study will determine the appropriate dose of veliparib with 
standard-dose concurrent chemoradiotherapy and consolidation chemotherapy by a 3 + 3 
cohort design.
Both 120 mg BID veliparib and 240 mg BID (or higher) have been used in Phase 2 and 
Phase 3 studies in combination with platinum doublet in different patient population.  In 


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Cohorts 1 – 5, the 120 mg BID dose of investigational agent (veliparib) in the 
consolidation portion was selected based on a randomized, double-blind placebo 
controlled Phase 2 study of carboplatin and paclitaxel ± veliparib for advanced metastatic 
NSCLC, and to ensure the capability to escalate veliparib dose in combination with 
Chemo-RT.  
Once the CRT RPTD is determined, a 6th cohort will be enrolled with subjects at 240 mg 
BID dose in the consolidation portion as indicated in Table 1.  The dose selection of 
240 mg BID was supported by safety data in Phase 1 studies with veliparib in 
combination with carboplatin/paclitaxel, an ongoing Phase 2 study of 240 mg BID of 
veliparib in combination of carboplatin/etopside for extended stage of small cell lung 
cancer, and a Phase 3 study of 300 mg BID veliparib in combination of 
carboplatin/paclitaxel in front line ovarian cancer patients.  As described in Section 3.0, 
preliminary data from this study show the combination is well-tolerated, showed delivery 
of carboplatin and paclitaxel were not substantially compromised, and suggested 
improved efficacy in subjects who received veliparib.
The maximum dose of veliparib/placebo for any subject in this study is 240 mg BID 
continuously during chemoradiotherapy followed by 240 mg BID for 7 of 21 days over 
2 cycles of consolidation chemotherapy.
6.0
Adverse Events
The investigator will monitor each subject for clinical and laboratory evidence of adverse 
events on a routine basis throughout the study.  The investigator will assess and record 
any adverse event in detail including the date of onset, event diagnosis (if known) or 
sign/symptom, severity, time course (end date, ongoing, intermittent), relationship of the 
adverse event to study drug, and any action(s) taken.  For serious adverse events 
considered as having "no reasonable possibility" of being associated with study drug or 
NSCLC, the investigator will provide an Other cause of the event.  For adverse events to 
be considered intermittent, the events must be of similar nature and severity.  Adverse 


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events, whether in response to a query, observed by site personnel, or reported 
spontaneously by the subject will be recorded.
All adverse events will be followed to a satisfactory conclusion.
6.1
Definitions
6.1.1
Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or 
clinical investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An adverse event can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal (investigational) 
product, whether or not the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an adverse event.  
Worsening in severity of a reported adverse event should be reported as a new adverse 
event.  Laboratory abnormalities and changes in vital signs are considered to be adverse 
events only if they result in discontinuation from the study, necessitate therapeutic 
medical intervention, and/or if the investigator considers them to be adverse events.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
adverse event if the surgery/procedure is being performed for a pre-existing condition and 
the surgery/procedure has been pre-planned prior to study entry.  However, if the 
pre-existing condition deteriorates unexpectedly during the study (e.g., surgery performed 
earlier than planned), the deterioration of the condition for which the elective 
surgery/procedure is being done will be considered an adverse event.


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6.1.2
Serious Adverse Events
If an adverse event meets any of the following criteria, it is to be reported to AbbVie as a 
serious adverse event (SAE) within 24 hours of the site being made aware of the serious 
adverse event.
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would 
have resulted in immediate fatality if medical 
intervention had not been taken.  This does not include 
an event that would have been fatal if it had occurred 
in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital 
for any length of time or prolongs the subject's
hospital stay.  This does not include an emergency 
room visit or admission to an outpatient facility 
hospitalization for respite care, or hospitalization due 
solely to progression of the underlying cancer.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly 
that results in fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially 
interferes with the activities of daily living of a study 
subject.  Disability is not intended to include 
experiences of relatively minor medical significance 
such as headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle).


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Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome
An important medical event that may not be 
immediately life-threatening or result in death or 
hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or 
surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life threatening, 
hospitalization, prolongation of hospitalization, 
congenital anomaly, or persistent or significant 
disability/incapacity).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an
important medical event.  Examples of such events 
include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug 
dependency or drug abuse. 
For serious adverse events with the outcome of death, the date and cause of death will be 
recorded on the appropriate case report form.
6.2
Adverse Events Expected Due to NSCLC or Progression of 
NSCLC
Adverse events that may be expected from primary NSCLC lesions or compression of 
adjacent thoracic structures are presented in Appendix C of the protocol.
These adverse events may occur alone or in various combinations and are considered 
expected adverse events in NSCLC subjects.
6.3
Adverse Event Severity
The study Investigator will rate the severity of each adverse event according to the 
National Cancer Institute Common Terminology Criteria for Adverse Events NCI 
CTCAE version 4.0.23
For adverse events not captured by the NCI CTCAE version 4.0, the Investigator will use 
the following definitions to rate the severity of each adverse event: 


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Mild
(Grade 1)
The adverse event is transient and easily tolerated by the subject.
Moderate
(Grade 2)
The adverse event causes the subject discomfort and interrupts the 
subject's usual activities.
Severe
(Grade 3 or 4)
The adverse event causes considerable interference with the subject's 
usual activities and may be incapacitating or life threatening.
Death
(Grade 5)
The adverse event resulted in death of the subject.
If a reported adverse event increases in severity, the initial adverse event should be given 
an outcome date and a new adverse event should be reported to reflect the change in 
severity.
For all reported serious adverse events that increase in severity, the supplemental CRFs 
also need to be updated and need to include the new AE serial number.
6.4
Relationship to Study Drug
The investigator will use the following definitions to assess the relationship of the adverse 
event to the use of study drug: 
Reasonable 
Possibility
An adverse event where there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
No Reasonable 
Possibility
An adverse event where there is no evidence to suggest a causal 
relationship between the study drug and the adverse event.
The investigator will assess the relationship of each adverse event to veliparib, to 
carboplatin, to radiotherapy, and to NSCLC.  Most events will be reasonably related to 
one treatment or to NSCLC, though some events may be reasonably related to more than 
one or to none.  For causality assessments, events assessed as having a reasonable 
possibility of being related to veliparib will be considered "associated."  Events assessed 
as having no reasonable possibility of being related to veliparib will be considered "not 


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associated."  In addition, when the investigator has not reported a causality or deemed it 
not assessable, AbbVie will consider the event associated.
If an investigator's opinion of no reasonable possibility of being related to veliparib, to 
carboplatin, to paclitaxel, to radiotherapy, and to NSCLC is given, an Other cause of 
event must be provided by the investigator for the serious adverse event.
6.5
Adverse Event Collection Period
All protocol-related adverse events will be collected from the signing of the study-specific 
informed consent until 30 days following discontinuation of study drug administration 
have elapsed.  All adverse events (regardless of whether they are protocol-related) will be 
collected from the time of study drug administration until 30 days following 
discontinuation of study drug administration have elapsed.  Adverse events are to be 
collected whether solicited or spontaneously reported by the subject.
Adverse event information will be collected as shown in Figure 3.
Figure 3.
Adverse Event Collection
Protocol Related
SAEs & Nonserious 
AEs*
SAEs and Nonserious AEs
Elicited and/or Spontaneously Reported
∀
∀
∀
∀
Consent 
Signed
Study 
Drug 
Start
Study 
Drug 
Stopped
30 Days
After Study 
Drug 
Stopped
*
Only if considered by the Investigator to be causally related to study-required procedures.
6.6
Adverse Event Reporting
6.6.1
Deaths
For this protocol, mortality is an efficacy endpoint.  Deaths that occur during the protocol 
specified adverse event reporting period (Section 6.5) that are more likely related to 


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disease progression will therefore be an expected adverse event and will not be an 
expedited report.
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be reported.  
The term "sudden death" should only be used for the occurrence of an abrupt and 
unexpected death due to presumed cardiac causes in a patient with or without pre-existing 
heart disease, within 1 hour of the onset of acute symptoms or, in the case of an 
unwitnessed death, within 24 hours after the patient was last seen alive and stable.  If the 
cause of death is unknown and cannot be ascertained at the time of reporting, 
"unexplained death" should be recorded on the Adverse Event eCRF.  If the cause of 
death later becomes available (e.g., after autopsy), "unexplained death" should be replaced 
by the established cause of death.
6.6.2
Lack of Efficacy or Worsening of Disease
Events that are clearly consistent with the expected pattern of progression of the 
underlying disease are also considered an expected outcome for this study and will not be 
subject to expedited reporting.  If there is any uncertainty as to whether an event is due to 
disease progression, it should be reported as an adverse event.
6.6.3
Reporting Serious Adverse Events
In the event of a serious adverse event, whether associated with study drug or not, the 
Investigator will notify Clinical Pharmacovigilance within 24 hours of the site being made 
aware of the serious adverse event by entering the serious adverse event data into the 
electronic data capture (EDC) system.  Serious adverse events that occur when the EDC 
system is not available should be sent on SAE Non-CRF paper forms to Clinical 
Pharmacovigilance within 24 hours of the site being made aware of the serious adverse 
event.


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Serious adverse events which are considered expected due to the underlying disease of 
NSCLC as described in Appendix C would not be expedited as individual safety case 
reports to regulatory authorities.
FAX to:
Email to:
For safety concerns, contact the Oncology Safety Team or physician at:
Oncology Group Safety Management
AbbVie
1 North Waukegan Road
North Chicago, IL  60064
Office:
Fax:
Email:
Primary Study Designated Physician:
AbbVie
1 North Waukegan Road
North Chicago, IL 60064
Office:
Fax:
Mobile:
Email:
In case of subject safety concerns or medical emergencies, should the Primary Study 
Designated Physician be unavailable, please call the following central back-up number:


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Phone:
The sponsor will be responsible for Suspected Unexpected Serious Adverse Reactions 
(SUSAR) reporting for the Investigational Medicinal Product (IMP) in accordance with 
Directive 2001/20/EC.  The reference document used for SUSAR reporting in the EU 
countries will be the most current version of the Investigator's Brochure for veliparib.  
The reference document used for SUSAR reporting in the EU countries will be the most 
current version of the Summary of Product Characteristics (SmPC) for 
paclitaxel/carboplatin.
6.7
Pregnancy
In the event of a positive pregnancy test, subjects must immediately discontinue study 
drug and must be discontinued from the study.  The Investigator must report the positive 
pregnancy test to the appropriate contact listed in protocol (Section 6.6) within 1 working 
day of the site becoming aware of the pregnancy.
All subjects should be informed that contraceptive measures should be taken throughout 
the study and for 6 months after discontinuing study drug.  Information regarding a 
pregnancy occurrence in a study subject and the outcome of the pregnancy will be 
collected.  The Investigator must follow the pregnancy to completion and provide an 
update to AbbVie after delivery.
Male subjects should be informed that contraceptive measures should be taken by their 
female partners.  If the subject's partner should become pregnant during the study, this 
should also be reported and data may be collected.  In the event of pregnancy occurring in 
the partner of an enrolled subject, written informed consent for release of medical 
information from the partner must be obtained prior to the collection of any pregnancy 
specific information and the pregnancy will be followed to outcome.
Pregnancy in a study subject is not considered an adverse event.  However, the medical 
outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 


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considered a serious adverse event and must be reported to AbbVie within 24 hours of the 
site becoming aware of the event.
6.8
Toxicity Management
All dose modifications (including dose delay, reduction, resumption, and discontinuation) 
are to be performed at the discretion of the Investigator.  Guidelines suggesting dose 
modifications based on prior studies with veliparib, carboplatin, and paclitaxel appear in 
Table 10 and Appendix D.  Study drug interruptions for events that are clearly not related 
to the study drug treatment, (e.g., underlying cancer, planned surgical procedures or acute 
viral illnesses), should not necessitate a dose reduction.  The AbbVie medical monitor is 
to be contacted for subjects who require more than a 2-week delay in the re-initiation of 
chemotherapy or more than 7-day delay in the re-initiation of radiotherapy.
Management of toxicity should be performed by investigators according to standard 
medical practice and according to local label for toxicity due to carboplatin or paclitaxel.  
Following dose reductions, re escalation of paclitaxel, carboplatin, or veliparib doses is 
not allowed.
6.8.1
Dose Limiting Toxicities
Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new 
dosing cohort is opened or until the recommended Phase 2 dose is identified.  A minimum 
of 3 subjects will be enrolled in each cohort.  Additional eligible subjects may be enrolled 
at the current dose level at the discretion of the Investigators and the AbbVie Medical 
Monitor.  From each cohort, subjects will be entered into the DLT assessment group of 
the intended cohort size in order of treatment.  Subjects considered evaluable for DLTs 
will be those in the assessment group who receive treatment through 1 cycle or have AEs 
meeting DLT criteria.  If a subject in the DLT assessment group becomes unevaluable, the 
subject will be replaced by the next-treated subject in the cohort.  The DLT period for 
each subject in the concurrent CRT dose escalation will be from start of veliparib dosing 
through 28 days following completion of CRT or until consolidation chemotherapy is 
initiated, and the DLT period for all patients at each dose level will end upon initiation of 


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next dose level.  The DLT period for each subject during consolidation chemotherapy 
dose (Cohort 6), will be 21 days from start of consolidation or until the start of Cycle 2 of 
the consolidation therapy or treatment discontinuation.  Any of the events as described in 
Section 5.2 that are considered by the investigator to be related to treatment will be 
considered a dose limiting toxicity (DLT).  At the time of dose escalation decisions, any 
events occurring in the DLT assessment group after the first cycle of therapy and any 
additional safety data available from cohort subjects not in the DLT assessment group will 
be taken into consideration.
Subjects experiencing DLTs will generally be discontinued from further participation in 
the study, but may continue at the same or a reduced dose with approval by the medical 
monitor if there is evidence of clinical benefit.
6.8.2
Determination of the MTD
The MTD will be determined as described in Section 5.5.1.  MTD, if identified, will be 
defined as the highest dose level at which less than or equal to 2 of 6 subjects or ≤ 33% of 
subjects experience the same DLT.
6.8.3
Determination of the RPTD
AbbVie will review available safety data from all subjects in the dose escalation portion 
of the study and determine the RPTD for veliparib during chemoradiotherapy and 
consolidation chemotherapy.  Subjects in the randomized portion of the study will receive 
the veliparib CRT RPTD or placebo during chemoradiotherapy and the veliparib 
consolidation RPTD or placebo during consolidation.  If an MTD is reached, the RPTD 
will not be a dose higher than the MTD and will be selected based on the types of DLTs 
which occur and the MTD identified.  If an MTD is not reached, then the RPTD will be 
defined based on the safety and available PK data.  The RPTD will not exceed 240 mg 
BID.


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6.8.4
Dose Modifications During Concurrent Therapy
The following are guidelines for delay and discontinuation of CRT treatments.  Doses that 
are missed during the weekly schedule of CRT will not be made up.  Any treatment delays 
will be documented.  If paclitaxel and/or carboplatin doses must be withheld for greater 
than 3 consecutive weeks, the drug(s) will be held permanently for the duration of 
concurrent therapy.  Veliparib should be interrupted if radiotherapy, paclitaxel, and 
carboplatin are interrupted for > 7 days.  After interruption, veliparib should be re-started 
2 days prior to the resumption of radiotherapy when possible.
6.8.4.1
Dose Modifications for Hematologic Toxicity
Hematologic Toxicity:  RT should be held for all Grade 4 hematologic toxicity except for 
Grade 4 lymphopenia, (at the discretion of the treating physician).  RT should be resumed 
when hematologic toxicity is ≤ Grade 3.
Toxicity
NCI CTCAE Grade (CTCAE v. 4.0) on 
the Day of Due Treatment*
Paclitaxel Dose at 
Start of Subsequent 
Cycles Of Therapy
Carboplatin Dose at Start of 
Subsequent Cycles Of 
Therapy
Neutropenia
3 (500 – 999/ mm3)
Hold therapya
Hold therapya
Neutropenia
4 (< 500/mm3)
Hold therapya
Hold therapya
Neutropenic fever
Hold therapya
Hold therapya
Thrombocytopenia
3 (25,000 – 49,999/mm3)
Hold therapya
Hold therapya
Thrombocytopenia
4 (< 24,999/mm3)
Hold therapya
Hold therapya
*
RT should be held for all Grade 4 hematologic toxicity except for Grade 4 lymphopenia, (at the discretion of the 
treating physician).  RT should be resumed when hematologic toxicity is ≤ Grade 3.
a.
Repeat lab work weekly and resume chemotherapy and veliparib based on this table.  If paclitaxel and/or 
carboplatin doses must be withheld for greater than 3 consecutive weeks, the drug(s) will be held permanently for 
the duration of concurrent therapy.


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6.8.4.2
Dose Modifications for Non-hematologic Toxicity
Non-Hematologic Toxicity:  RT should be held for all Grade 4 non-hematologic toxicity 
in or outside the treatment field and resumed only when toxicity is ≤ Grade 2.
Worst Toxicity NCI CTCAE 
Grade (CTCAE 4.0)
Paclitaxel Dose At Start of 
Subsequent Cycles Of Therapy
Carboplatin Dose at Start of 
Subsequent Cycles Of Therapy
Neuropathy
Grade 2
Hold therapy until Grade ≤ 1;
restart at full dose
Maintain dose level
Neuropathy
Grade 3 or 4
Discontinue therapy
Hold therapy, until ≤ Grade 2
Other non-hematologic 
toxicitiesa
Grade 3 or 4
Hold therapy, until ≤ Grade 2
Hold therapy, until ≤ Grade 2
a.
RT should be held for all Grade 4 non-hematologic toxicity in or outside the treatment field and resumed only 
when toxicity is ≤ Grade 2.
Note:
If there is a decline in performance status to ≥ 2 for greater than 2 weeks while under treatment, radiotherapy 
should be held with no further chemotherapy administered.  Re-evaluate patient after one week for resumption 
of radiotherapy.
6.8.4.3
Dose Modifications for In-Field, Non-Hematologic Toxicity 
During Concurrent Therapy
Treatment Modification for In-field Non-Hematologic Toxicity
In-field
CTCAE
Toxicity
Grade
RT
Paclitaxel
Carboplatin
Esophagus/pharynx*
(on day of RT)
4
Hold treatment 
Until ≤ Grade 2
Hold treatment 
Until ≤ Grade 2
Hold treatment 
Until ≤ Grade 2
Esophagus/pharynx*
(on day of chemo)
3
No change or hold 
≤ 5 days
Hold treatment 
Until ≤ Grade 2
Hold treatment 
Until ≤ Grade 2
Pulmonary
4
Discontinue
Discontinue
Discontinue
Pulmonary
3
Hold treatment 
Until ≤ Grade 2
Hold treatment 
Until ≤ Grade 2
Hold treatment 
Until ≤ Grade 2
Skin
4
Hold treatment 
Until ≤ Grade 2
Hold treatment 
Until ≤ Grade 2
Hold treatment 
Until ≤ Grade 2
*
Radiation esophagitis or dermatitis will use CTCAE v4.0.  The grading for esophagitis as per CTCAE v. 4.0 is:
Grade 1:  Asymptomatic; clinical or diagnostic observations only; intervention not indicated.
Grade 2:  Symptomatic; altered eating/swallowing; oral supplements indicated.


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Grade 3:  Severely altered eating/swallowing; tube feeding, TPN or hospitalization indicated.
Grade 4:  Life-threatening consequences; urgent operative intervention indicated.
Radiotherapy will be continued without interruption even if chemotherapy and/or 
veliparib/placebo are held for toxicity or any other reason.  However, if radiotherapy is 
held for toxicity, chemotherapy and/or veliparib will be held as well.
6.8.5
Dose Modifications During Consolidation Therapy
Table 10.
Suggested Guidelines for Veliparib + Paclitaxel/Carboplatin 
Independent Dose Reduction
Dose Level
Carboplatin
Paclitaxel
Veliparib/Placebo
Starting Dose Level (for 
subjects participating in 
Cohort 6)
AUC 6
200 mg/m2
240 mg BID
Starting Dose Level –1
120 mg BID
Dose Level –2
AUC 5
175 mg/m2
80 mg BID
Dose Level –3
AUC 4
150 mg/m2
60 mg BID
6.8.5.1
Veliparib Dose Reductions and Delays
The following are guidelines for dose reduction, delay and discontinuation of Veliparib:
1.
Veliparib is to be discontinued if both carboplatin and paclitaxel are discontinued.
2.
For any subject who experiences Grade 3/4 toxicity which is not attributable to 
paclitaxel/carboplatin or the underlying disease, the Veliparib dose is to be held 
until the toxicity resolves to Grade 1 or lower or to baseline if Grade 2 is present at 
the time of study entry.  Upon resuming Veliparib treatment, the dose is to be 
reduced one dose level.  Any dose reduction beyond 40 mg BID is to result in 
Veliparib discontinuation.
3.
If a subject begins Veliparib on Day –2 for consolidation therapy (both cycles) but 
subsequently experiences an event requiring delay of the paclitaxel/carboplatin 
dosing on Day 1, the subject is to stop Veliparib dosing immediately.  Upon 


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resolution of the event, the subject may restart the current cycle by repeating 
Day –2 and Day –1.  For such delays, a new Veliparib supply will be dispensed to 
restart the cycle at Day –2.
4.
For any ≥ Grade 2 event of seizure attributed to Veliparib, Veliparib is to be 
discontinued and the event should be discussed with the AbbVie medical monitor.
6.8.5.2
Paclitaxel/Carboplatin Dose Reductions and Delays
For carboplatin and/or paclitaxel dose modifications, the Investigator should follow 
procedures as defined in the locally approved product label or applicable Summary of 
Product Characteristics (SmPC).  Suggested dose reductions for paclitaxel/carboplatin if 
above information is not available are outlined in Appendix D.  If the Investigator 
considers an event attributable to carboplatin and/or paclitaxel, the Investigator may 
consider reducing the dose of both agents.
All toxicities are to be resolved to grade 1 or less prior to initiation of a new cycle of 
therapy, with the exception of anemia, alopecia, neuropathy, and non-treatment related 
clinically insignificant laboratory abnormalities.
If chemotherapy must be withheld due to hematologic toxicity, CBC and platelet counts 
should be obtained weekly until the counts reach the lower limits for treatment as 
outlined.  The treatment schedule will then proceed in the usual sequence.
For subjects who miss any one dose of veliparib/placebo in the 48 hours prior to the start 
of any portion of backbone therapy (Week 1 Day 1 of concurrent therapy or Day 1 of 
either cycle of consolidation), that therapy will be held and veliparib/placebo restarted 
(from Day –3 for concurrent and Day –2 for consolidation).
Hematologic Toxicity
For absolute neutrophil count (ANC) < 1,500/mm3 or platelet count < 100,000/mm3 on 
Day 1 of each cycle, treatment is to be delayed until recovery of ANC and platelet count 


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above these values.  For febrile neutropenia or for grade 4 thrombocytopenia, carboplatin 
and paclitaxel doses are to be reduced by one dose level.
If the subject experiences fever with neutropenia, then neutrophil growth factors are to be 
given based on local standard of care guidelines or ASCO guidelines.22
Non-Hematological Toxicity
Gastrointestinal Toxicity
For grade 3 or 4 nausea/vomiting despite maximal anti-emetic therapy or for grade 3 or 4 
stomatitis, the dose of carboplatin and paclitaxel are to be reduced by 1 dose level.  
Nausea, vomiting, and stomatitis are to have resolved to grade 1 before initiation of a new 
cycle of therapy.
If the stomatitis has not resolved to grade 1 or less within 3 weeks, the subject's study 
treatment is to be discontinued.
Hepatic Toxicity
For bilirubin > 1.5 × ULN with increased ALT above ULN that is attributed to protocol 
therapy, paclitaxel is to be held until bilirubin is ≤ 1.5 × ULN, and the dose is to be 
reduced by one level when treatment is resumed.
For ALT > 5 × ULN with bilirubin < 1.5 × ULN that is attributed to protocol therapy, 
paclitaxel dose is to be reduced by one level.
Neurologic Toxicity
For grade 2 neuropathy, paclitaxel dose is to be reduced to Dose Level –1.  For grade 3/4 
neuropathy, paclitaxel dose is to be held until neuropathy is grade 2, and the dose is to be 
reduced to Dose Level –2 when treatment is resumed.  The dose of carboplatin will not be 
reduced for neurologic toxicity.


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7.0
Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol.  The 
principal investigator is responsible for complying with all protocol requirements, and 
applicable global and local laws regarding protocol deviations.  If a protocol deviation 
occurs (or is identified) after a subject has been enrolled, the principal investigator is 
responsible for notifying Independent Ethics Committee (IEC)/Independent Review 
Board (IRB) regulatory authorities (as applicable), and the following AbbVie Clinical 
Monitor(s):
Clinical Team Lead:
AbbVie
1 North Waukegan Road
North Chicago, IL  60064
Office:
Fax:
Email:
Medical Monitor:
AbbVie
1 North Waukegan Road
North Chicago, IL 60064
Office:
Fax:
Mobile
Email:
Such contact must be made as soon as possible to permit a review by AbbVie to 
determine the impact of the deviation on the subject and/or the study.
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analytical Plans
For subjects in the Phase 1 portion, the date of enrollment is defined as the first day of 
study drug administration.  For subjects in the randomized Phase 2 portion, the date of 


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randomization (enrollment) is defined as the date that the IRT issued a randomization 
number.
ORR will be performed on all dosed subjects in Phase 1 portion of the study.  The 
primary, secondary, and tertiary efficacy analyses will be performed on all subjects in the 
randomized Phase 2 portion of the study.
Safety analyses will be performed separately for the Phase 1 and Phase 2 portions.  All 
subjects who receive at least one dose of the study drug will be included in the safety 
analysis.
Unless otherwise noted, data will be summarized for Phase 1 and Phase 2 subjects 
separately.
8.1.1
Baseline Characteristics
All baseline summary statistics and analyses will be based on characteristics obtained 
prior to the initiation of study drug (or randomization for non-treated subjects).  Unless 
otherwise stated, baseline for a given variable will be defined as the last value for that 
variable obtained prior to the first dose of study drug.  
8.1.1.1
Demographics
Continuous demographic data (e.g., age, height, and weight) will be summarized with 
means, standard deviations, medians, and minimum and maximum values.  Frequencies 
and percentages will be computed for categorical data (e.g., sex, race, and performance 
status).
8.1.1.2
Medical History
Frequencies and percentages will be computed for each medical history parameter.


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8.1.2
Efficacy Endpoints
8.1.2.1
Primary Efficacy Endpoint
The primary efficacy endpoint is progression-free survival (PFS).  Progression-Free 
Survival will be defined as the number of days from the date of randomization to the date 
of earliest radiographic disease progression or death.  All radiographic disease progression 
will be included regardless whether the event occurred while the subject was taking study 
drug or had previously discontinued study drug.  If the subject does not experience 
radiographic disease progression or death, then the data will be censored at the date of the 
last disease assessment.
8.1.2.2
Secondary Efficacy Endpoints
Secondary efficacy endpoints include overall survival, objective response rate, and 
duration of overall response.
Overall Survival
Overall survival will be defined as the number of days from the date of randomization to 
the date of death.  For subjects who did not die, their data will be censored at the date of 
last study visit or the last known date to be alive, whichever is later.  
Objective Response Rate
The proportion of subjects with objective response as assessed by the investigator using 
RECIST version 1.1 will be evaluated for randomized subjects.
Duration of Overall Response
Duration of overall response will be defined as the number of days from the date of 
first response (CR or PR) to the earliest documentation of radiographic progressive 
disease or death due to disease progression.  If a subject is still responding, then the 
subject's data will be censored at the date of the subject's last available disease 


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assessment.  For subjects who never experience response, the subject's data will not be 
included in the analysis.  
8.1.2.3
Tertiary Efficacy Endpoints
In addition to the primary and secondary efficacy analyses, tertiary efficacy analyses of 
performance status and quality of life will be performed.
Performance Status
Changes and/or percent changes from baseline will be summarized using descriptive 
statistics for each scheduled post-baseline visit and for the Final Visit for ECOG 
performance status (as shown in Table 2).  Post-baseline measurements more than 30 days 
after the last dose of study drug will not be included.  Subjects that do not have a baseline 
measurement or do not have any post-baseline measurements will not be included.
Quality of Life Measures
Changes and/or percent changes from baseline will be summarized using descriptive 
statistics for each scheduled post-baseline visit and for the Final Visit for quality of life 
measures using EORTC QLQ-C15-PAL and EORTC QLQ-LC13 questionnaire (as 
shown in Table 2).
8.1.3
Primary Analysis of Efficacy
PFS will be analyzed by Kaplan Meier methodology and compared between Arm A 
(concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/veliparib) and Arm C (concurrent 
paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation 
paclitaxel/carboplatin/placebo), using a log-rank test stratified by tumor volume.  A 
two-sided, stratified log-rank test p-value will be provided.  Median PFS time will be 
calculated and 95% confidence interval for median PFS time will be presented.


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8.1.4
Secondary Analysis of Efficacy
Progression-Free Survival (Arm B versus Arm C)
PFS will be analyzed by Kaplan Meier methodology and compared between Arm B 
(concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/placebo) and Arm C, using a log-rank test stratified by tumor 
volume.  A two-sided, stratified log-rank test p-value will be provided.  Median PFS time 
will be calculated and 95% confidence interval for median PFS time will be presented.
Overall Survival
OS will be analyzed by Kaplan Meier methodology and compared between Arm A and 
Arm C as well as between Arm B and Arm C, using a log-rank test stratified by tumor 
volume.  A two-sided, stratified log-rank test p-value will be provided.  Median OS time 
will be calculated and 95% confidence interval for median OS time will be presented.
Objective Response Rate
The objective response rate will be estimated and compared between Arm A and Arm C 
as well as between Arm B and Arm C, using a Cochran-Mantel-Haenszel test stratified by 
tumor volume.  A two-sided, stratified CMH test p-value will be provided.  In addition, a 
95% confidence interval will be constructed for the estimated proportions. 
Duration of Overall Response
The distribution of duration of overall response (DOR) will be estimated for each 
treatment arm using Kaplan-Meier methodology.  Median DOR will be estimated and a 
95% confidence interval will be presented for each treatment arm.
8.1.5
Tertiary Analysis of Efficacy
Quality of Life
Changes and/or percent changes from baseline will be summarized using descriptive 
statistics for each scheduled post-baseline visit and for the Final Visit for quality of life 


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measures using EORTC QLQ-C15-PAL and EORTC QLQ-LC13 questionnaire.  Changes 
and/or percent changes from baseline to each visit will be compared between Arm A and 
Arm C as well as between Arm B and Arm C using an analysis of covariance with 
treatment arm as the factor and baseline value as a covariate.
ECOG Performance Status
Changes and/or percent changes from baseline in ECOG performance status will be 
summarized using descriptive statistics for each scheduled post-baseline visit and for the 
final visit.  Post-baseline measurements more than 30 days after the last dose of study 
drug will not be included.  Subjects that do not have a baseline measurement or do not 
have any post-baseline measurements will not be included.  Changes and/or percent 
changes from baseline to each visit will be compared between Arm A and Arm C as well 
as between Arm B and Arm C using an analysis of covariance with treatment arm as the 
factor and baseline value as a covariate.
8.1.6
Safety Assessments
A safety analysis will be performed for all subjects participating in the study unless 
otherwise indicated.  Safety analyses will be performed for Phase 1 and Phase 2 
separately.  The following will be included in these analyses:
8.1.6.1
Duration of Study Drug
A summary of the number of days and/or cycles subjects were exposed to study drug will 
be provided.
8.1.6.2
Adverse Event
Analyses of adverse events will include only "treatment-emergent" events, i.e., those that 
have an onset on or after the day of the first dose of study drug (veliparib or placebo).
Analyses will not include those that have an onset greater than 30 days after the last dose 
of study drug.


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Treatment-emergent adverse events will be coded and summarized by system organ class 
and preferred term according to the Medical Dictionary for Regulatory Activities 
(MedDRA) adverse event coding dictionary.  The percentage of subjects experiencing an 
adverse event at a given NCI CTCAE version 4.0 grade, and relationship to study drug 
will be provided.  For Phase 1, all summaries will be done by dose level.  For Phase 2, 
comparisons of the percentages of subjects experiencing an adverse event between Arm A 
and Arm C as well as between Arm B and Arm C will be performed using Fisher's exact 
test.
8.1.6.3
Serious Adverse Event
Serious adverse events will be summarized using the same methods as adverse events 
described above in Section 8.1.6.2.
8.1.6.4
Death
The number of subject deaths will be summarized 1) for deaths occurring while the 
subject was still receiving study drug in this study, 2) for deaths occurring off treatment 
within 30 days after the last dose of study drug, and 3) for all deaths in this study 
regardless of the number of days after the last dose of study drug.
8.1.6.5
Longitudinal Analyses of Laboratory and Vital Signs Data
Changes from baseline will be analyzed for each scheduled post-baseline visit and for the 
final visit for blood chemistry and hematology parameters, as well as urinalysis and vital 
sign parameters.  If more than one measurement exists for a subject on a particular day, an 
arithmetic average will be calculated.  This average will be considered to be that subject's 
measurement for that day.  Post-baseline measurements more than 30 days after the last 
dose of randomized study drug will not be included.  Subjects that do not have a baseline 
measurement or do not have any post-baseline measurements will not be included.  For 
Phase 1, changes from baseline will be analyzed by dose level at each scheduled visit.


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For Phase 2, comparisons of the differences in mean changes from baseline between Arm 
A and Arm C as well as between Arm B and Arm C will be made using ANCOVA with 
treatment group as the factor and baseline as a covariate.
8.1.6.6
Analyses of Laboratory Data Using NCI CTCAE
Where applicable, blood chemistry and hematology determinations will be categorized 
according to NCI CTCAE version 4.0 grades, and shifts from baseline NCI CTCAE 
version 4.0 grades to maximum and final post-baseline grades will be assessed.  The 
baseline and final grades will be defined respectively as the grade of the last measurement 
collected prior to the first dose of study drug, and as the grade of the last post-baseline 
measurement collected no more than 30 days after the last dose of study drug.  If multiple 
values are available for a post-baseline measurement, then the value with the highest NCI 
CTCAE grade will be used in the assessment of shift.  Comparisons of the number of 
subjects experiencing a shift from baseline grades of 0 to 2 or no grade to maximum 
post-baseline grades of 3 to 4, and from baseline grades of 0 to 2 or no grade to final 
post-baseline grades of 3 to 4 between Arm A and Arm C as well as between Arm B and 
Arm C will be performed using Fisher's exact tests.  Additional analyses including all 
measurements collected, regardless of the number of days after the last dose of study 
drug, will be performed.
Detailed listings of data for subjects experiencing NCI CTCAE Grade 3 to 4 blood 
chemistry and hematology values will be provided.  All measurements collected, 
regardless of the number of days after the last dose of study drug, will be included in these 
listings.
8.1.6.7
Analyses of Vital Signs Using Criteria for Potentially 
Clinically Significant Vital Sign Values
Detailed listings of data for subjects experiencing potentially clinically significant vital 
sign values according to the AbbVie-defined criteria for vital sign values will be provided.  
All measurements collected, regardless of the number of days after the last dose of study 
drug, will be included in these listings.


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8.1.7
Timing of Efficacy Analyses and Safety Evaluations
At the time when the 107th PFS events are observed, all efficacy and safety data as of this 
time will be retrieved and entered into the clinical database prior to breaking the study 
blind.  When the data collection is completed and reviewed for completeness and all data 
management quality assurance (QA) and quality control (QC) procedures are performed, 
the study blind will be broken and clinical database data will be extracted for 
documentation and statistical analyses of the efficacy and safety data.
Overall survival (OS) will be collected on all subjects after they discontinue from the 
study until the study is concluded by AbbVie.  After all survival data have been collected 
and entered into the clinical database, the clinical database will be extracted once again 
for documentation and a "Final OS Analysis" will be performed on this dataset.
8.1.8
Interim Analysis
To ensure subject safety, an internal data monitoring committee (DMC) will review 
un-blinded safety data when 45 subjects in Phase 2 portion of the study have completed 
chemoradiotherapy, reached an event of disease progression or death, or discontinued the 
study.
Only safety will be evaluated at interim analysis.  AbbVie clinical and statistical 
personnel directly responsible for the conduct of the study will not have access to either 
the treatment codes or the interim analyses prepared for the DMC.
8.2
Determination of Sample Size
Approximately 50 subjects will be enrolled in the dose escalation portion of the study.
Assuming a hazard ratio of 0.6 for Arm A (Concurrent 
paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/veliparib) versus Arm C (Concurrent 
paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation 
paclitaxel/carboplatin/placebo), a total of 71 PFS events in Arm A and Arm C combined 


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will provide an expected 95% confidence interval of 0.38 to 0.96 for the estimated hazard 
ratio.  Assuming a hazard ratio of 0.75 for Arm B (Concurrent 
paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/placebo) versus Arm C, a total of 107 PFS events will be observed 
across all three arms at the time when 71 PFS events are observed for Arm A and Arm C 
combined.  A total of approximately 156 subjects (52 subjects per treatment arm) will be 
enrolled into Phase 2 portion of the study to obtain the 107 PFS events.
8.3
Randomization Methods
In Phase 2, the IRT will randomize subjects in a 1:1:1 ratio to one of the treatment arms as 
follows:
A.  Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by 
consolidation  paclitaxel/carboplatin/veliparib  
B.  Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by 
consolidation  paclitaxel/carboplatin/placebo
C.  Concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by 
consolidation  paclitaxel/carboplatin/placebo
Subject randomization will be stratified by tumor volume (≤ 90 versus > 90 cm3) and 
smoking history (current smoker versus former smoker versus never smoked).  The 
stratification factors used for the randomization should be the last values on or prior to the 
date of randomization and should be consistent with those on the eCRF.
9.0
Ethics
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB)
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigator's Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 


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any other necessary documents be reviewed by an IEC/IRB.  The IEC/IRB will review the 
ethical, scientific and medical appropriateness of the study before it is conducted.  
IEC/IRB approval of the protocol, informed consent and subject information and/or 
advertising, as relevant, will be obtained prior to the authorization of drug shipment to a 
study site.
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  The investigator will be required to submit, 
maintain and archive study essential documents according to ICH GCP.
Any serious adverse events that meet the reporting criteria, as dictated by local 
regulations, will be reported to both responsible Ethics Committees and Regulatory 
Agencies, as required by local regulations.  During the conduct of the study, the 
investigator should promptly provide written reports (e.g., ICH Expedited Reports, and 
any additional reports required by local regulations) to the IEC/IRB of any changes that 
affect the conduct of the study and/or increase the risk to subjects.  Written documentation 
of the submission to the IEC/IRB should also be provided to AbbVie.
9.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
study conduct and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical investigator are specified in Appendix A.
9.3
Subject Information and Consent
The investigator or his/her representative will explain the nature of the study to the 
subject, and answer all questions regarding this study.  Prior to any study-related 
screening procedures being performed on the subject, the informed consent statement will 
be reviewed and signed and dated by the subject, the person who administered the 
informed consent, and any other signatories according to local requirements.  A copy of 
the informed consent form will be given to the subject and the original will be placed in 


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the subject's medical record.  An entry must also be made in the subject's dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.
Pharmacogenetic analysis will only be performed if the subject has voluntarily signed and 
dated a separate pharmacogenetic informed consent, approved by an IRB/IEC, after the 
nature of the testing has been explained and the subject has had an opportunity to ask 
questions.  The separate pharmacogenetic informed consent must be signed before the 
pharmacogenetic testing is performed.  If the subject does not consent to the 
pharmacogenetic testing, it will not impact the subject's participation in the study.
For subjects participating in Cohort 1 – 5, archived tissue analysis will only be performed 
if the subject has voluntarily consented for tissue sampling on the informed consent, 
approved by an IRB/IEC, after the nature of the testing has been explained and the subject 
has had an opportunity to ask questions.  If the subject does not consent to the archived 
tissue analysis, it will not impact the subject's participation in the study.  Subjects in 
Cohort 6 must consent to provide available archival tumor for analysis.  It is recognized 
that the availability of the samples suitable for analysis may not be known at the time of 
consent for all subjects.
10.0
Source Documents and Case Report Form 
Completion
10.1
Source Documents
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents.


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The investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents.
10.2
Case Report Forms
Case report forms (CRF) must be completed for each subject screened/enrolled in this 
study.  These forms will be used to transmit information collected during the study to 
AbbVie and regulatory authorities, as applicable.  The CRF data for this study are being 
collected with an electronic data capture (EDC) system called Rave® provided by the 
technology vendor Medidata Solutions Incorporated, NY, USA.  The EDC system and the 
study-specific electronic case report forms (eCRFs) will comply with Title 21 CFR 
Part 11.  The documentation related to the validation of the EDC system is available 
through the vendor, Medidata, while the validation of the study-specific eCRFs will be 
conducted by AbbVie and will be maintained in the Trial Master File at AbbVie.
The investigator will document subject data in his/her own subject files.  These subject 
files will serve as source data for the study.  All eCRF data required by this protocol will 
be recorded by investigative site personnel in the EDC system.  All data entered into the 
eCRF will be supported by source documentation.
The investigator or an authorized member of the investigator's staff will make any 
necessary corrections to the eCRF.  All change information, including the date and person 
performing the corrections, will be available via the audit trail, which is part of the EDC 
system.  For any correction, a reason for the alteration will be provided.  The eCRFs will 
be reviewed periodically for completeness, legibility, and acceptability by AbbVie 
personnel (or their representatives).  AbbVie (or their representatives) will also be allowed 
access to all source documents pertinent to the study in order to verify eCRF entries.  The 
principal investigator will review the eCRFs for completeness and accuracy and provide 
his or her electronic signature and date to eCRFs as evidence thereof.
Medidata will provide access to the EDC system for the duration of the study through a 
password-protected method of internet access.  Such access will be removed from 


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investigator sites at the end of the site's participation in the study.  Data from the EDC 
system will be archived on appropriate data media (CD-ROM, etc.) and provided to the 
investigator at that time as a durable record of the site's eCRF data.  It will be possible for 
the investigator to make paper printouts from that media.
11.0
Data Quality Assurance
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
12.0
Use of Information
Any pharmacogenetic research that may be done using DNA samples from this study will 
be experimental in nature and the results will not be suitable for clinical decision making 
or patient management.  Hence, neither the investigator, the subject, nor the subject's 
physician (if different from the investigator) will be informed of individual subject 
pharmacogenetic results, should analyses be performed, nor will anyone not directly 
involved in this research.  Correspondingly, genetic researchers will have no access to 
subject identifiers.  Individual results will not be reported to anyone not directly involved 
in this research other than for regulatory purposes.  Aggregate pharmacogenetic 
information from this study may be used in scientific publications or presented at medical 
conventions.  Pharmacogenetic information will be published or presented only in a way 
that does not identify any individual subject.
13.0
Completion of the Study
The investigator will conduct the study in compliance with the protocol and complete the 
study within the timeframe specified in the contract between the investigator and AbbVie.  
Continuation of this study beyond this date must be mutually agreed upon in writing by 
both the investigator and AbbVie.  The investigator will provide a final report to the 
IEC/IRB following conclusion of the study, and will forward a copy of this report to 
AbbVie or their representative.


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The investigator must retain any records related to the study according to local 
requirements.  If the investigator is not able to retain the records, he/she must notify 
AbbVie to arrange alternative archiving options.
AbbVie will select the signatory investigator from the investigators who participate in the 
study.  Selection criteria for this investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigator's Signature for Study Reports.
The end-of-study is defined as the date of the last subject's last visit.


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14.0
Investigator's Agreement
1.
I have received and reviewed the Investigator's Brochure for veliparib and the 
product labeling for carboplatin and paclitaxel.
2.
I have read this protocol and agree that the study is ethical.
3.
I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines.
4.
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.
5.
I agree that all electronic signatures will be considered the equivalent of a 
handwritten signature and will be legally binding.
Protocol Title: 
A Phase 1 Dose Escalation and Phase 2 Randomized, 
Placebo-Controlled Study of the Efficacy and Tolerability of 
Veliparib in Combination with Paclitaxel/Carboplatin-Based 
Chemoradiotherapy Followed by Veliparib and 
Paclitaxel/Carboplatin Consolidation in Subjects with Stage III 
Non-Small Cell Lung Cancer (NSCLC)
Protocol Date:
15 August 2017
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)


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15.0
Reference List
1.
Globocan 2012:  Estimated Cancer Incidence, Mortality and Prevalence Worldwide 
in 2012.  Available from:  www.globocan.iarc.fr.
2.
Weir HK, Thun MJ, Hankey BF, et al.  Annual report to the nation on the status of 
cancer, 1975-2000, featuring the uses of surveillance data for cancer prevention 
and control.  J Natl Cancer Inst.  2003;95(17):1276-99.
3.
National Comprehensive Cancer Networks guidelines, Version 2.  2013.  Available 
from:  http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
4.
Perez CA, Stanley K, Rubin P, et al.  A prospective randomized study of various 
irradiation doses and fractionation schedules in the treatment of inoperable non 
oat-cell carcinoma of the lung.  Preliminary report by the Radiation Therapy 
Oncology Group.  Cancer.  1980;45(11):2744-53.
5.
Dillman RO, Herndon J, Seagren SL, et al.  Improved survival in stage III 
non-small-cell lung cancer:  seven-year follow-up of cancer and leukemia group B 
(CALGB) 8433 trial.  J Natl Cancer Inst.  1996;88(17):1210-5.
6.
Le Chevalier T, Arriagada R, Tarayre M, et al.  Significant effect of adjuvant 
chemotherapy on survival in locally advanced non-small-cell lung carcinoma.  
J Natl Cancer Inst.  1992;84(1):58.
7.
Sause W, Kolesar P, Taylor S IV, et al.  Final results of phase III trial in regionally 
advanced unresectable non-small cell lung cancer:  Radiation Therapy Oncology 
Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group.  
Chest.  2000;117(2):358-64.
8.
Schaake-Koning C, van den Bogaert W, Dalesio O, et al.  Effects of concomitant 
cisplatin and radiotherapy on inoperable non-small-cell lung cancer.  N Engl J 
Med.  1992;326(8):524-30.
9.
Belani CP, Choy H, Bonomi P, et al.  Combined chemoradiotherapy regimens of 
paclitaxel and carboplatin for locally advanced non-small-cell lung cancer:  a 
randomized phase II locally advanced multi-modality protocol.  J Clin Oncol.  
2005;23(25):5883-91.


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10.
Cox JD.  Are the results of RTOG 0617 mysterious?  Int J Radiat Oncol Biol Phys.  
2012;82(3):1042-4.
11.
Yamamoto N, Nakagawa K, Nishimura Y, et al.  Phase III study comparing 
second- and third-generation regimens with concurrent thoracic radiotherapy in 
patients with unresectable stage III non-small-cell lung cancer:  West Japan 
Thoracic Oncology Group WJTOG0105.  J Clin Oncol.  2010;28(23):3739-45.
12.
Bradley JD, Moughan J, Graham MV, et al.  A phase I/II radiation dose escalation 
study with concurrent chemotherapy for patients with inoperable stages I to III 
non-small-cell lung cancer:  phase I results of RTOG 0117.  Int J Radiat Oncol Biol 
Phys.  2010;77(2):367-72.
13.
Choy H, Akerley W, Safran H, et al.  Multiinstitutional phase II trial of paclitaxel, 
carboplatin, and concurrent radiation therapy for locally advanced non-small-cell 
lung cancer.  J Clin Oncol.  1998;16(10):3316-22.
14.
Vokes EE, Herndon JE 2nd, Kelley MJ, et al.  Induction chemotherapy followed by 
chemoradiotherapy compared with chemoradiotherapy alone for regionally 
advanced unresectable stage III Non-small-cell lung cancer:  Cancer and Leukemia 
Group B.  J Clin Oncol.  2007;25(13):1698-704.
15.
Virág L, Szabó C.  The therapeutic potential of poly(ADP-ribose) polymerase 
inhibitors.  Pharmacol Rev.  2002;54(3):375-429.
16.
DePinho RA, Polyak K.  Cancer chromosomes in crisis.  Nat Genet.  
2004;36(9):932-4.
17.
Curtin NJ, Wang LZ, Yiakouvaki A, et al.  Novel poly(ADP-ribose) polymerase-1 
inhibitor, AG14361, restores sensitivity to temozolomide in mismatch repair 
deficient cells.  Clin Cancer Res.  2004;10(3):881-9.
18.
AbbVie.  Veliparib (ABT-888) Investigator Brochure Edition 7.  17 June 2013.


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19.
Coleman RL, Sill M, Aghajanian CA, et al.  Phase II Evaluation of the Potent, 
Highly Selective PARP Inhibitor Veliparib in the Treatment of Persistent or 
Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in 
Patients Who Carry a Germline BRCA1 or BRCA2 Mutation – a Gynecologic 
Oncology Group Study.  SGO 2013 Annual Meeting on Women's Cancer; March 
2013; Los Angeles, CA.
20.
Rugo HS, Olopade O, DiMichele A, et al.  Veliparib/carboplatin plus standard 
neoadjuvant therapy for high-risk breast cancer:  First efficacy results from the I 
SPY 2 TRIAL.  In:  Proceedings of the 2013 San Antonio Breast Cancer 
Symposium; 13 December, 2013; San Antonio, TX.  Abstract S5-02.
21.
Ramalingam S.  A phase I study of veliparib (ABT-888) in combination with 
carboplatin and paclitaxel in advanced solid malignancies.  J Clin Oncol.  
2012(suppl; abstr 3049).
22.
American Society of Clinical Oncology (ASCO) guidelines.  Available from:  
http://www.asco.org/quality-guidelines/guidelines.
23.
National Cancer Institute Common Terminology Criteria for Adverse Events NCI 
CTCAE Version 4.0, http://evs.nci.nih.gov/ftp1/CTCAE/About.html.
24.
Carboplatin [package insert].  Irvine, CA; Teva Parenteral Medicinces, Inc., 2011.
25.
Paclitaxel [package insert].  Bedford, OH; Ben Venue Laboratories, Inc., 2010.
26.
FDA Carboplatin Dosing Notification, 2010.  Available from:  
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm228974.htm.
27.
International Commission on Radiation Units and Measurements (ICRU) Reports 
50 and 62 on Prescribing, Recording, and Reporting Photon Beam Therapy.  
Available from:  http://www.icru.org/.
28.
Peters S, Adjei AA, Gridelli C, et al.  Metastatic non-small-cell lung cancer 
(NSCLC):  ESMO Clinical Practice Guidelines for diagnosis, treatment and 
follow-up.  Ann Oncol.  2012;23Suppl7:vii56-64. 
29.
Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines version 1.1, 
Available from:  http://www.eortc.org/investigators-area/recist.


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Appendix A.
Responsibilities of the Clinical Investigator
Clinical research studies sponsored by AbbVie are subject to the Good Clinical Practices 
(GCP) and local regulations and guidelines governing the study at the site location.  In 
signing the Investigator Agreement in Section 14.0 of this protocol, the investigator is 
agreeing to the following:
1.
Conducting the study in accordance with the relevant, current protocol, making 
changes in a protocol only after notifying AbbVie, except when necessary to 
protect the safety, rights or welfare of subjects.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed 
consent and ethics committees [e.g., independent ethics committee (IEC) or 
institutional review board (IRB)] review and approval of the protocol and 
amendments.
4.
Reporting adverse experiences that occur in the course of the investigation(s) to 
AbbVie and the site director.
5.
Reading the information in the Investigator's Brochure/safety material provided, 
including the instructions for use and the potential risks and side effects of the 
investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the 
study about their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making 
those records available for inspection by representatives of AbbVie and/or the 
appropriate regulatory agency, and retaining all study-related documents until 
notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and 
approved the initial clinical investigation and all amendments.


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9.
Reporting promptly, all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others, to the appropriate individuals 
(e.g., coordinating investigator, institution director) and/or directly to the ethics 
committees and AbbVie.
10.
Following the protocol and not make any changes in the research without ethics 
committee approval, except where necessary to eliminate apparent immediate 
hazards to human subjects.


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Appendix B.
List of Protocol Signatories
Name
Title
Functional Area
Clinical
GDSM
Clinical
Clinical
Statistics
Clinical Pharmacology & 
Pharmacometrics
Bioanalysis
Biometrics


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Appendix C.
Adverse Events Expected Due to NSCLC or Progression of NSCLC
Preferred Term (MedDRA Version 13.1)
Pleural effusion
Malignant pleural effusion
Metastases to pleura
Dyspnoea
Cough
Non-cardiac chest pain
Haemoptysis*
Oesophageal obstruction
Pneumonia*
Vocal cord paralysis
Dysphonia
Dysphagia
Superior vena cava syndrome
Horner's syndrome
Metastases to bone
Metastases to lymph nodes
Metastases to liver
Metastases to spine
Metastases to the mediastinum
Metastases to pleura
Metastases to adrenals
Metastases to meninges
Metastases to central nervous system
Metastatic pain
Cancer pain
Tumour pain
Fatigue
Asthenia
Pulmonary embolism*
Blood Antidiuretic Hormonal Abnormal (SIADH)
Cushing's syndrome


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Preferred Term (MedDRA Version 13.1)
Cachexia
Shock*
Septic shock*
Deep vein thrombosis*
Lower respiratory tract infection*
Respiratory tract infection*
Upper respiratory tract infection*
Opportunistic infection*
Viral infection*
Fungal infection*
Bacterial infection*
Pulmonary haemorrhage*
Lung abscess*
Empyema*
Sepsis*
Lymphadenopathy
Decreased appetite
Malaise
Weight decreased
Headache
Pain excluding chest pain
Pyrexia
*
Includes life threatening or fatal events.


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Appendix D.
Suggested Guidelines for Paclitaxel/Carboplatin Dose Delay or 
Reduction During Consolidation Chemotherapy 
Adverse Event
Carboplatin Dose
Paclitaxel Dose
Grade 3/4 Neutropenia 
without fever
Wait until ANC ≥ 1,500/mm3.
Wait until ANC ≥ 1,500/mm3.
Grade 3/4 Febrile Neutropenia
Reduce to Dose Level –1 for 
1st episode and Dose Level –2 for 
2nd episode.  Consider Prophylactic 
G CSF after 1st episode
Reduce to Dose Level –1 for 
1st episode and Dose
Level –2 for 2nd episode.  
Consider Prophylactic G-CSF 
after 1st episode. 
Grade 3/4 nausea, vomiting 
despite standard supportive 
care, or grade 3/4 Stomatitis 
Dose Level –1 for 1st episode and 
Dose Level –2 for 2nd episode.  
Dose Level –1 for 1st episode 
and Dose Level –2 for 2nd
episode.  
Grade 4 Thombocytopenia
Dose Level –1 for 1st episode and 
Dose Level –2 for 2nd episode.  
Dose Level –1 for 1st episode 
and Dose Level –2 for 2nd
episode.  
Bilirubin  > 1.5 × ULN with 
increased ALT above ULN
No Change
Hold until recovery; then reduce 
to Dose Level –1 for 1st episode 
and Dose Level –2 for 
2nd episode.  
ALT > 5 × ULN with 
Bilirubin < 1.5 × ULN
No Change
Reduce to Dose Level –1 for 
1st episode and Dose Level –2 
for 2nd episode.  
Grade 2 Neuropathy 
No Change
Reduce to Dose Level –1.
Grade 3/4 Neuropathy 
No Change
Hold until recovery to Grade 2.  
Reduce to Dose Level –2.
Any other Grade 3/4 toxicity
Discuss with AbbVie medical 
monitor
Discuss with AbbVie medical 
monitor


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Appendix E.
RECIST Version 1.1 for Tumor Response (PFS)
Response criteria will be assessed using RECIST version 1.1.  Changes in the measurable 
lesions over the course of therapy must be evaluated using the criteria listed below.
Eligibility
Subjects with measurable disease at baseline can have objective tumor response evaluated 
by RECIST version 1.1.  Measurable disease is defined by the presence of at least 
one measurable lesion.  If the measurable disease is restricted to a solitary lesion, its 
neoplastic nature should be confirmed by cytology/histology if possible.
Measurability
Measurable Lesions
Lesions accurately measured in at least one dimension 
with a minimum size of: 
!
Longest diameter ≥ 10 mm (CT scan slice
thickness no greater than 5 mm)
!
10 mm caliper measurement by clinical exam
Non-Measurable Lesions
All other lesions, including small lesions (longest 
diameter < 10 mm) as well as truly non-measurable 
lesions.  Lesions considered truly non-measurable 
include:  leptomeningeal disease, ascites, 
pleural/pericardial effusion, inflammatory breast disease, 
lymphangitic involvement of skin or lung and also 
abdominal masses that are not confirmed and followed by 
imaging techniques.
Measurable Malignant 
Lymph Nodes
To be considered pathologically enlarged and 
measurable, a lymph node must be ≥ 15 mm in short axis 
when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm).  At baseline 
and in follow-up, only the short axis will be measured 
and followed.
Non-Measurable 
Malignant Lymph Nodes
Pathological lymph nodes with ≥ 10 to < 15 mm short 
axis.


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Special Considerations 
Regarding Lesion 
Measurability
Bone lesions
Lytic bone lesions or mixed lytic-blastic lesions, with 
identifiable soft tissue components, that can be evaluated 
by cross sectional imaging techniques such as MRI/CT 
can be considered as measurable lesions if the soft tissue 
component meets the definition of measurability 
described above.
Blastic bone lesions are non-measurable.
Cystic lesions
Lesions that meet the criteria for radiographically defined 
simple cysts should not be considered as malignant 
lesions (neither measurable nor non measurable) since 
they are, by definition, simple cysts.
'Cystic lesions' thought to represent cystic metastases can 
be considered as measurable lesions, if they meet the 
definition of measurability described above.
However, if non-cystic lesions are present in the same 
patient, these are preferred for selection as target lesions.
Lesions with prior local treatment
Tumor lesions situated in a previously irradiated area, or 
in an area subjected to other loco-regional therapy, are 
usually not considered measurable unless there has been 
demonstrated progression in the lesion.
All measurements should be taken and recorded in metric notation, using calipers if 
clinically assessed.  All baseline evaluations should be performed as closely as possible to 
the beginning of treatment and not more than 28 days before the beginning of the 
treatment.
The same method of assessment and the same technique should be used to characterize 
each identified and reported lesion at baseline and during follow-up.
Clinical lesions will only be considered measurable when they are superficial (e.g., skin 
nodules and palpable lymph nodes) and ≥ 10 mm diameter as assessed using calipers.  For 


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the case of skin lesions, documentation by color photography including a ruler to estimate 
the size of the lesion is recommended.
Methods of Measurement
Conventional CT should be performed with cuts of 5 mm or less in slice thickness 
contiguously.  This applies to tumors of the chest and abdomen.  A scale should be 
incorporated into all radiographic measurements.  MRI can be performed if required by 
local law, but should have sponsor approval.
If prior to enrollment, it is known a subject is not able to undergo CT scans with IV 
contrast due to allergy or renal insufficiency, the decision as to whether a non-contrast CT 
or MRI should be used to evaluate the subject at baseline and follow-up should be guided 
by the tumor type under investigation and the anatomic location of the disease.  For 
subjects who develop contraindications to contrast after baseline contrast CT is done, the 
decision as to whether non-contrast CT or MRI should be made based upon discussion 
with the AbbVie medical monitor.
For accurate objective response evaluation, ultrasound (US) should not be used to 
measure tumor lesions.
The utilization of endoscopy and laparoscopy for objective tumor evaluation is not 
advised.  However, such techniques can be useful in confirming complete pathological 
response when biopsies are obtained.
Cytology and histology can be used to differentiate between partial response (PR) and 
complete response (CR) in rare cases.
Baseline Documentation of "Target" and "Non-Target" Lesions
All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, 
representative of all involved organs should be identified as target lesions and recorded 
and measured at baseline.  Target lesions should be selected on the basis of their size 
(lesions with the longest diameter), be representative of all involved organs, but in 


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addition should be those that lend themselves to reproducible repeated measurements.  
Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion.  
Lymph nodes merit special mention since they are normal anatomical structures which 
may be visible by imaging even if not involved by tumor.  Pathological nodes which are 
defined as measurable and may be identified as target lesions must meet the criterion of a 
short axis of ≥ 15 mm by CT scan.  Only the short axis of these nodes will contribute to 
the baseline sum.  The short axis of the node is the diameter normally used by radiologists 
to judge if a node is involved by solid tumor.  Nodal size is normally reported as 
two dimensions in the plane in which the image is obtained (for CT scan this is almost 
always the axial plane).  The smaller of these measures is the short axis.  For example, an 
abdominal node which is reported as being 20 mm × 30 mm has a short axis of 20 mm 
and qualifies as a malignant, measurable node.  In this example, 20 mm should be 
recorded as the node measurement.  All other pathological nodes (those with short axis 
≥10 mm but < 15 mm) should be considered non-target lesions.  Nodes that have a short 
axis < 10 mm are considered non-pathological and should not be recorded or followed.
A sum of the longest diameter (LD) for all target lesions will be calculated and reported as 
the baseline sum LD.  If lymph nodes are to be included in the sum, then as noted above, 
only the short axis is added into the sum.  The baseline sum LD will be used as reference 
by which to characterize the objective tumor response.
All other lesions (or sites of disease) including pathological lymph nodes should be 
identified as non-target lesions and should also be recorded at baseline.  Measurements of 
these lesions are not required, but the presence (stable, increasing or decreasing) or 
absence of each should be noted throughout follow-up.


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Evaluation of Target Lesions
Complete Response (CR):
The disappearance of all target lesions.  Any pathological lymph nodes (whether target or 
non-target) must have reduction in short axis to < 10 mm.
Partial Response (PR):
At least a 30% decrease in the sum of diameters of target lesions, taking as reference the 
baseline sum diameters.
Progressive Disease (PD):
At least a 20% increase in the sum of the LD of target lesions, taking as reference the 
smallest sum LD recorded since the treatment started (baseline or after) or the appearance 
of one or more new lesions.  In addition to the relative increase of 20%, the sum must also 
demonstrate an absolute increase of at least 5 mm.
Stable Disease (SD):
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, 
taking as reference the smallest sum LD since the treatment started (baseline or after).
Assessment of Target Lesions:
Lymph nodes identified as target lesions should always have the actual short axis 
measurement recorded (measured in the same anatomical plane as the baseline 
examination), even if the nodes regress to below 10 mm on study.  This means that when 
lymph nodes are included as target lesions, the 'sum' of lesions may not be zero even if 
complete response criteria are met, since a normal lymph node is defined as having a short 
axis of < 10 mm.  For PR, SD and PD, the actual short axis measurement of the nodes is 
to be included in the sum of target lesions.


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All lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (< 5 mm).  
However, sometimes target lesions or lymph nodes become too small to measure.  If it is 
in the opinion of the radiologist that the lesion has likely disappeared, the measurement 
should be recorded as 0 mm.  If the lesion is believed to be present, but too small to 
measure, a default value of 5 mm should be assigned (as derived from the 5 mm CT slice 
thickness).  The measurement of these lesions is potentially non-reproducible; therefore 
providing this default value will prevent false responses or progression based upon 
measurement error.
Evaluation of Non-Target Lesions
Complete Response (CR):
The disappearance of all non-target lesions and normalization of tumor marker level.  All 
lymph nodes must be non-pathological in size (< 10 mm short axis).
Non-CR/Non-PD:
Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level 
above the normal limits.
Progressive Disease (PD):
Unequivocal progression of existing non-target lesions.
In this setting, to achieve 'unequivocal progression' on the basis of non-target disease, 
there must be an overall level of substantial worsening in non-target disease such that, 
even in the presence of SD or PR in target disease, the overall tumor burden has increased 
sufficiently to merit discontinuation of therapy.  A modest 'increase' in the size of one or 
more non-target lesions is usually not sufficient to qualify for unequivocal progression 
status.  The designation of overall progression solely on the basis of change in non-target 
disease in the face of SD or PR of target disease will therefore be extremely rare.


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New Lesions
The appearance of new malignant lesions denotes disease progression.  While there are no 
specific criteria for the identification of new radiographic lesions, the findings of a new 
lesion should be unequivocal; i.e., not attributable to differences in scanning technique, 
timing of scanning, phase of contrast administration, change in imaging modality or 
finding thought to represent something other than tumor (e.g., some 'new' bone lesions 
may be simply healing or flare of pre-existing lesions).  A lesion identified on a follow-up 
study in an anatomical location that was not scanned at baseline is considered a new 
lesion and will indicate disease progression.  An example of this is the patient who has 
visceral disease at baseline and while on study has a CT or MRI brain ordered which 
reveals metastases.  The patient's brain metastases are considered evidence of progressive 
disease even if he/she did not have brain imaging at baseline.
If a new lesion is equivocal (e.g., too small to measure), continued therapy and follow-up 
evaluation will clarify if it represents truly new disease.  If repeat scans confirm there is a 
new lesion, then progression should be declared using the date of the initial scan.


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Appendix F.
Protocol Amendment:  List of Changes
The summary of changes is listed in Section 1.1.
Specific Protocol Changes:
Section 1.0  Title Page
"Sponsor/Emergency Contact:" previously read:
Sponsor/Emergency 
  Contact:
1 North Waukegan Road
North Chicago, IL  60064
Phone:
Fax:
Has been changed to read:
Sponsor/Emergency 
  Contact:
AbbVie
1 North Waukegan Road
North Chicago, IL 60064
Phone:
Fax:
Section 1.2  Synopsis
Previously read:
AbbVie Inc.
Protocol Number:  M14-360
Name of Study Drug:  Veliparib/ABT-888
Phase of Development:  1/2
Name of Active Ingredient:  Not Applicable
Date of Protocol Synopsis:  29 September 2016
Protocol Title:  A Phase 1 Dose Escalation and Phase 2 Randomized, Placebo-Controlled Study of the 
Efficacy and Tolerability of Veliparib in Combination with Paclitaxel/Carboplatin-Based 
Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Subjects with 
Stage III Non-Small Cell Lung Cancer (NSCLC)


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Objective(s):  
The primary objectives of the study are to establish the recommended Phase 2 dose (RPTD) of veliparib 
in combination with concurrent Paclitaxel/Carboplatin-based chemoradiotherapy (Phase 1 portion) and to 
assess whether the addition of oral veliparib versus placebo to Paclitaxel/Carboplatin-based 
chemoradiotherapy with Paclitaxel/Carboplatin consolidation will improve progression-free survival 
(PFS) in patients with Stage III non-small cell lung cancer (Phase 2 portion).
The secondary objectives of the study are to assess overall survival (OS), objective response rate (ORR), 
duration of overall response (DOR), safety and tolerability of veliparib versus placebo added to standard 
therapy (Phase 2 portion).
The tertiary objectives are to assess Quality of Life (QoL) (Phase 2 portion) and ECOG performance 
status.  In addition, biomarkers including, but not limited to, defects in DNA-repair genes will be 
assessed in correlation with safety and efficacy data.
Investigator(s):  Multicenter
Study Site(s):  Approximately 50 – 75
Study Population:  Subjects with Stage III NSCLC suitable for definitive chemoradiotherapy (CRT) 
who have not received prior therapy for NSCLC
Number of Subjects to be Enrolled:  Approximately 30 in the dose escalation portion and 
approximately 156 in the randomized portion of the study
Methodology:  
This two-phase study consists of 1) dose-escalation of veliparib to determine an RPTD for combination 
with concurrent paclitaxel/carboplatin-based CRT; and followed by 2) a randomized, double-blinded 
study to determine whether veliparib improves outcome relative to placebo when added to 
Paclitaxel/Carboplatin-based CRT followed by consolidation Paclitaxel/Carboplatin in subjects with 
previously untreated Stage III NSCLC.
In the dose escalation phase of the study, subjects will receive veliparib in combination with carboplatin 
AUC 2+ paclitaxel 45 mg/m2 + thoracic radiotherapy.  Radiation delivery will be over no more than 
9 weeks by 3-dimensional conformal radiotherapy or intensity modulated radiotherapy (IMRT), and the 
total dose will be 60 – 63 Gy.  The first cohort of at least 3 – 6 subjects will receive veliparib 60 mg BID 
throughout CRT.  Based on tolerability, subsequent cohorts will receive doses of veliparib from 40 mg 
BID to 240 mg BID.  The consolidation dose of veliparib will be 120 mg BID + carboplatin AUC 6 + 
paclitaxel 200 mg/m2 for up to two 21-day cycles.


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Methodology (Continued):
Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new dosing cohort is 
opened or until the recommended Phase 2 dose is identified.  A minimum of 3 subjects will be enrolled in 
each cohort.  Additional eligible subjects may be enrolled at the current dose level at the discretion of the 
Investigators and the AbbVie Medical Monitor.  From each cohort, subjects will be entered into the DLT 
assessment group of the intended cohort size in order of treatment.  Subjects considered evaluable for
DLTs will be those that receive treatment through 1 cycle or have AEs meeting DLT criteria.  If a subject 
in the DLT assessment group becomes unevaluable, the subject will be replaced by the next-treated 
subject in the cohort.  The DLT period for each subject will be from start of veliparib dosing through 
28 days following completion of CRT or until consolidation chemotherapy is initiated, and the DLT 
period for all patients at each dose level will end upon initiation of next dose level.
Dose limiting toxicities are the following events that are considered by the investigator group to be 
related to treatment:
1.
Radiation induced Grade 3 or greater cardiac toxicity (e.g., myocarditis, pericarditis, heart failure, 
ventricular dysfunction, myocardial infarction). 
2.
Radiation induced myelopathy/myelitis (does not include L'Hermitte's syndrome).
3.
Radiation-related pneumonitis resulting in delay in radiotherapy, chemotherapy (CRT or 
consolidation) or veliparib of more than 3 weeks or early discontinuation of RT (total dose < 50 Gy).
4.
G4 or greater esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment 
interruption of > 7 days despite medical management.
5.
G2 or greater seizure.
6.
Grade 4 or greater neutropenia for > 7 days or neutropenic fever (defined as ANC < 500 and a 
temperature of 38.5°C or above).
7.
Grade 4 or greater thrombocytopenia.
8.
Grade 4 diarrhea or nausea/vomiting despite appropriate antiemetic therapy lasting > 48 hours.
9.
Any other toxicity resulting in delay in radiotherapy, chemotherapy, or veliparib of more than 
14 days or early discontinuation of RT (total dose < 50 Gy).
10. All other non-hematologic toxicities of Grade 3 or greater, with the following exceptions:
a.
Anorexia
b.
Fatigue
c.
Grade 3 infection
d.
Grade 3 AST/ALT elevations ≤ 7 days
e.
Infusion reactions.  Patients with Grade 3 or worse infusion reactions will be removed from 
study and replaced and will not be considered evaluable for DLT
f.
Grade 3 or 4 lymphopenia
g.
Grade 3 or 4 electrolyte abnormalities that are corrected to Grade 2 or less in less than 48 hours
Following the dose escalation portion of the trial, the RPTD will be determined by the sponsor, and at the 
discretion of the sponsor, the Phase 2 portion of the study will begin with patient randomization in a 
1:1:1 ratio to the treatment arms as follows:
A. Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/veliparib


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Methodology (Continued):
B.
Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/placebo
C.
Concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation 
paclitaxel/carboplatin/placebo
Subject randomization will be stratified by tumor volume (≤ 90 versus > 90 cm3) and smoking history 
(current smoker versus former smoker versus never smoked).  Screening procedures, QoL assessment, 
and baseline radiographic tumor assessments will be performed within 28 days prior to randomization.
Concurrent chemoradiotherapy (CRT) will consist of radiotherapy (RT) using either 3D conformal RT or 
IMRT plus paclitaxel, (45 mg/m2 as a 60 minute infusion), immediately followed by carboplatin, 
(AUC 2 mg/mL/min as a 30 minute infusion) weekly beginning on Day 1 of radiotherapy.  Veliparib (or 
placebo), will be administered continuously beginning 3 days prior to RT through one day after RT 
completion.
Consolidation chemotherapy will begin no more than 8 weeks following RT.  Subjects who require 
> 8 weeks to recover from toxicities resulting from CRT should not receive consolidation chemotherapy.  
Consolidation chemotherapy will consist of paclitaxel, (200 mg/m2 as a 3 hour infusion, immediately 
followed by carboplatin, AUC 6 mg/mL/min as a 30 minute infusion) on Day 1 of each 21-day cycle for 
up to 2 cycles.  Veliparib (or Placebo), 120 mg BID, will begin on Day –2 (2 days prior to the start of 
paclitaxel/carboplatin infusion) and will continue through Day 5 of each 21-day cycle.  
Subjects who experience toxicities due to carboplatin, paclitaxel, RT, or veliparib/placebo may require a 
delay in the dosing schedule or a dose modification.
Radiographic tumor assessments will be conducted at baseline, prior to consolidation chemotherapy, at 
24 weeks after start of treatment, every 8 weeks until one year after beginning therapy, then every 
12 weeks.  Beginning 12 weeks after randomization, progression will be determined based on Response 
Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.  Progression prior to that time will be 
determined by the Investigator.  A QoL assessment as measured by the EORTC QLQ-C15-PAL and the 
companion symptom module EORTC QLQ-LC13 will be performed at Screening, prior to consolidation 
chemotherapy, at 24 weeks after start of treatment, every 8 weeks until one year after beginning therapy 
and at the final visit.
After completion of protocol therapy, subjects will be observed without further therapy until progression.  
The visit at which an investigator identifies disease progression or at which a subject meets other criteria 
for study discontinuation will be considered the final visit.  All subjects with a final visit < 30 days after 
the last dose of drug will have one Follow-Up Visit approximately 30 days after the Final Visit.
If a subject is discontinued from the study with an ongoing adverse event or an unresolved clinically 
significant laboratory result, the site will attempt to provide follow-up until a satisfactory clinical 
resolution of the laboratory results or adverse event is achieved.
To ensure subject safety, an internal data monitoring committee (DMC) will review un-blinded safety 
data when approximately 45 subjects in the Phase 2 portion of the study have completed CRT, reached an 
event of disease progression or death, or discontinued the study.
Diagnosis:  Stage III NSCLC


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Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion (Phase 1 and Randomized Phase 2):
!
Subject must be ≥ 18 years of age;
!
Subject must have histologically or cytologically confirmed Stage III NSCLC.  When pleural fluid 
is visible on the CT scan or on a chest x-ray, a thoracentesis is required to confirm that the pleural 
fluid is serous AND cytologically negative.  Effusions that are minimal (i.e., not visible on chest 
x-ray) or that are too small to safely tap are exempted from the requirement for thoracentesis. 
!
Subjects in the randomized portion of the study must have measurable disease per RECIST 
version 1.1 criteria;
!
Subjects must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) 
< 35%;
!
Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 – 1;
!
Subject must have adequate hematologic, renal, hepatic, and lung function as follows: 
o
Bone marrow:  Absolute Neutrophil count (ANC) ≥ 1,500/μL; Platelets ≥ 100,000/mm3; 
Hemoglobin ≥ 9.0 g/dL (without transfusion);
o
Renal function:  calculated creatinine clearance ≥ 50 mL/min by the Cockcroft-Gault formula;
o
Hepatic function and enzymes:  aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) ≤ 2.5 × the upper limit of normal (ULN) of institution's normal range; 
Bilirubin ≤ 1.5 × ULN; subjects with Gilbert's syndrome may have a bilirubin ≥ 1.5 × ULN of 
central laboratory normal range; 
o
Pulmonary function tests (PFTs) including FEV1 within 12 weeks prior to randomization; for 
FEV1, the best value obtained pre- or post-bronchodilator must be ≥ 1.2 liters/second and/or 
≥50% predicted.
!
Female subjects of childbearing potential (i.e., those who are not postmenopausal for at least 1 year 
or surgically sterile by bilateral tubal ligation, bilateral oophorectomy or hysterectomy) and their 
male partner should practice at least one of the methods of birth control listed below for at least 
6 months after treatment with chemotherapy.  Male subjects and their female partners of 
childbearing potential should practice at least one of the methods of birth control listed below for 
at least 6 months after treatment with chemotherapy:
o
Total abstinence from sexual intercourse (if it is the subject's preferred and usual lifestyle; 
beginning a minimum one complete menstrual cycle prior to study drug administration and to 
extend 6 months after treatment);
o
Vasectomized subject or partner(s), vasectomy (males);
o
Intrauterine device (females);
o
Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with 
spermicidal jellies or creams; both males and females);
o
Hormonal contraceptives (oral, parenteral or transdermal) for at least 90 days prior to study 
drug administration (females).  If hormonal contraceptives are used, the subject and her 
partner should also use a single barrier method.
!
Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics 
Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of and Screening for 
study-specific procedures.


Veliparib
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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Exclusion:  
!
Subject with prior chemotherapy or radiotherapy for current NSCLC; subjects curatively treated 
for past early stage NSCLC greater than 3 years ago may be included;
!
Subject with prior exposure to PARP inhibitors;
!
Subjects with known hypersensitivity to carboplatin, paclitaxel, or formulations containing 
polyethoxylated castor oil (Cremophor);
!
Subject with prior mediastinal or thoracic radiotherapy.  Prior tangential RT to prior breast 
cancer is acceptable;
!
Subject with major surgery in the 4 weeks prior to randomization (VATS and/or 
mediastinoscopy is not considered major surgery);
!
Subject with a previous or concurrent malignancy except for treated basal cell or squamous cell 
skin cancer, in situ cervical cancer, or other cancer for which the patient received potentially 
curative treatment and has been disease-free for 3 years or is considered cured by the 
investigator if has been disease-free for less than 3 years;
!
Any medical condition, which in the opinion of the study investigator, places the subject at an 
unacceptably high risk for toxicities, or any subject circumstance that prohibits trial participation 
according to local law;
!
Subject is pregnant or lactating;
!
Subject with sensory peripheral neuropathy of ≥ Grade 2 at baseline;
!
Subject is unable to swallow medication;
!
Subjects with prior history of seizure within the prior 12 months.
Investigational Product:
Veliparib (ABT-888) or Placebo
Dose(s):
60 – 240 mg BID (concurrent chemoradiotherapy); 120 mg BID 
(consolidation)
Mode of Administration:
Oral
Reference Therapy:
Carboplatin 
Dose(s):
AUC 2 mg/mL/min (concurrent chemoradiotherapy); 
AUC 6 mg/mL/min (consolidation)
Mode of Administration:
Intravenous
Duration of Treatment:  
Subjects without clinical progression of disease and with tolerable side effects should continue to receive 
treatment until completion of all prescribed cycles (chemoradiotherapy plus 2 cycles of consolidation 
chemotherapy).


Veliparib
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138
Criteria for Evaluation:
Efficacy:
Progression-free survival (PFS) will be derived according to radiographic progression per RECIST 
version 1.1 (beginning with the second scan after completion of CRT) or death.  Radiographic tumor 
assessments for response will be conducted at baseline, prior to consolidation chemotherapy, at 24 weeks 
after start of treatment, every 8 weeks until one year after beginning therapy, then every 12 weeks until 
radiographic progression or death.  Subjects who require additional therapy, withdraw consent, or are lost 
to follow-up prior to radiographic progression will be censored at that time for the analysis of PFS.
Overall survival (OS) will be determined by the Investigator until radiographic progression.  After 
radiographic progression, survival information will be collected via the electronic CRF at 8-week 
intervals (or as requested by sponsor to support data analysis).
Objective response rate (ORR), and duration of overall response (DOR) will be derived per RECIST 
version 1.1.  Radiographic tumor assessments for response will be conducted at baseline, prior to 
consolidation chemotherapy, at 24 weeks after start of treatment, every 8 weeks until one year after 
beginning therapy, then every 12 weeks until radiographic progression or death.  Subjects who require 
additional therapy, withdraw consent, or are lost to follow-up prior to radiographic progression will be 
censored at that time for the analysis of DOR.
ECOG performance status will be determined by the Investigator at each assessment.  A quality of life 
assessment as measured by the EORTC QLQ-C15-PAL and the companion symptom module EORTC 
QLQ-LC13 will be performed at screening, prior to consolidation chemotherapy, at 24 weeks after start 
of treatment, every 8 weeks until one year after beginning therapy and at the final visit.
Pharmacokinetic:
Blood samples for veliparib assay will be collected for the determination of pharmacokinetic parameters 
of veliparib such as apparent oral clearance (CL/F) and volume of distribution (V/F).
Pharmacodynamic:
Research to find biomarkers that may serve as surrogates for clinical endpoints in future veliparib studies 
or that may be predictive of veliparib activity will be conducted.  Serum, plasma, blood and archived 
tissue samples (optional) will be collected at designated time points throughout the study.  Study-specific 
core biopsies are requested but are not required.
Safety:
Adverse events, laboratory profiles, physical examinations and vital signs will be assessed throughout the 
study.  Results will be tabulated for each subject and summary statistics will be computed for each 
sampling time and each parameter.


Veliparib
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Statistical Methods:
The following efficacy endpoint will be analyzed using data obtained from subjects in Phase 1:
Objective Response Rate (ORR)
The proportion of subjects with objective response as assessed by the investigator using RECIST 
version 1.1 will be calculated for all dosed subjects. 
The following efficacy endpoints will be analyzed using data obtained from subjects in Phase 2:
Progression-Free survival (PFS)
Progression-Free Survival will be defined as the number of days from the date of randomization to the 
date of earliest radiographic disease progression or death.  All radiographic disease progression will be 
included regardless whether the event occurred while the subject was taking study drug or had previously 
discontinued study drug.  If the subject does not experience radiographic disease progression or death, 
then the data will be censored at the date of the last disease assessment.
Overall Survival (OS)
Overall survival will be defined as the number of days from the date of randomization to the date of 
death.  For subjects who did not die, their data will be censored at the date of last study visit or the last 
known date to be alive, whichever is later.
Objective Response Rate (ORR) 
The proportion of subjects with objective response as assessed by the investigator using RECIST 
version 1.1 will be evaluated for randomized subjects. 
Duration of Overall Response (DOR)
Duration of overall response will be defined as the number of days from the date of first response (CR or 
PR) to the earliest documentation of radiographic progressive disease or death due to disease progression.  
If a subject is still responding, then the subject's data will be censored at the date of the subject's last 
available disease assessment.  For subjects who never experience response, the subject's data will not be 
included in the analysis.
Quality of life (QoL) Measures
Changes and/or percent changes from baseline will be summarized using descriptive statistics for each 
scheduled post-baseline visit and for the Final Visit for quality of life measures using the EORTC 
QLQ-C15-PAL and EORTC QLQ-LC13 questionnaires.  The QoL will be used as an exploratory 
endpoint and not tested against pre-specified hypothesis.
Performance Status
Changes and/or percent changes from baseline will be summarized using descriptive statistics for each 
scheduled post-baseline visit and for the Final Visit for ECOG performance status.  Post-baseline 
measurements more than 30 days after the last dose of study drug will not be included.  Subjects that do 
not have a baseline measurement or do not have any post-baseline measurements will not be included.
Efficacy Analysis:
The primary Phase 2 efficacy analysis will test if concurrent paclitaxel/carboplatin/radiotherapy/veliparib 
followed by consolidation paclitaxel/carboplatin/veliparib (Arm A) will improve PFS versus concurrent 
paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo 
(Arm C).


Veliparib
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Statistical Methods (Continued):
Efficacy Analysis (Continued):
The secondary Phase 2 efficacy analyses will test (in the following order):  
1) if concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/placebo (Arm B) results in improved Progression-Free survival (PFS) versus 
Arm C; 
2a) if Arm A or 
2b) if Arm B results in improved overall survival (OS) versus Arm C; 
3a) if Arm A or 
3b) if Arm B results in improved overall response rate (ORR) versus Arm C;
4a) if Arm A or 
4b) if Arm B results in improved duration of overall response (DOR) versus Arm C.
Sample Size:
Assuming a hazard ratio of 0.6 for Arm A (Concurrent paclitaxel/carboplatin/radiotherapy/veliparib 
followed by consolidation paclitaxel/carboplatin/veliparib) versus Arm C (Concurrent 
paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo), a 
total of 71 PFS events in Arm A and Arm C combined will provide an expected 95% confidence interval 
of 0.38 to 0.96 for the estimated hazard ratio.  Assuming a hazard ratio of 0.75 for Arm B (Concurrent 
paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/placebo) 
versus Arm C, a total of 107 PFS events will be observed across all three arms at the time when 71 PFS 
events are observed for Arm A and Arm C combined.  A total of approximately 156 subjects (52 subjects 
per treatment arm) will be enrolled into the Phase 2 portion of study to obtain the 107 PFS events.


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Has been changed to read:
AbbVie Inc.
Protocol Number:  M14-360
Name of Study Drug:  Veliparib/ABT-888
Phase of Development:  1/2
Name of Active Ingredient:  Not Applicable
Date of Protocol Synopsis:  15 August 2017
Protocol Title:  A Phase 1 Dose Escalation and Phase 2 Randomized, Placebo-Controlled Study of the 
Efficacy and Tolerability of Veliparib in Combination with Paclitaxel/Carboplatin-Based 
Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Subjects with 
Stage III Non-Small Cell Lung Cancer (NSCLC)
Objective(s):  
The primary objectives of the study are to establish the recommended Phase 2 dose (RPTD) of veliparib 
in combination with concurrent Paclitaxel/Carboplatin-based chemoradiotherapy and consolidation with 
Paclitaxel/Carboplatin-based chemotherapy (Phase 1 portion) and to assess whether the addition of oral 
veliparib versus placebo to Paclitaxel/Carboplatin-based chemoradiotherapy with Paclitaxel/Carboplatin 
consolidation will improve progression-free survival (PFS) in patients with Stage III non-small cell lung 
cancer (Phase 2 portion).
The secondary objectives of the study are to assess overall survival (OS), objective response rate (ORR), 
duration of overall response (DOR), safety and tolerability of veliparib versus placebo added to standard 
therapy (Phase 2 portion).
The tertiary objectives are to assess Quality of Life (QoL) (Phase 2 portion) and ECOG performance 
status.  In addition, biomarkers including, but not limited to, defects in DNA-repair genes will be 
assessed in correlation with safety and efficacy data.
Investigator(s):  Multicenter
Study Site(s):  Approximately 50 – 75
Study Population:  Subjects with Stage III NSCLC suitable for definitive chemoradiotherapy (CRT) 
who have not received prior therapy for NSCLC
Number of Subjects to be Enrolled:  Approximately 50 in the dose escalation portion and 
approximately 156 in the randomized portion of the study.
Methodology:  
This two-phase study consists of 1) dose-escalation of veliparib to determine an RPTD for combination 
with concurrent paclitaxel/carboplatin-based CRT; and followed by 2) a randomized, double-blinded 
study to determine whether veliparib improves outcome relative to placebo when added to 
Paclitaxel/Carboplatin-based CRT followed by consolidation Paclitaxel/Carboplatin in subjects with 
previously untreated Stage III NSCLC.


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Methodology (Continued):
In the dose escalation phase of the study, subjects will receive veliparib in combination with carboplatin 
AUC 2+ paclitaxel 45 mg/m2 + thoracic radiotherapy.  Radiation delivery will be over no more than 
9 weeks by 3-dimensional conformal radiotherapy or intensity modulated radiotherapy (IMRT), and the 
total dose will be 60 – 63 Gy.  The first cohort of at least 3 – 6 subjects will receive veliparib 60 mg BID 
throughout CRT.  Based on tolerability, subsequent cohorts will receive doses of veliparib from 40 mg 
BID to 240 mg BID.  As the CRT RPTD dose is explored (Cohorts 1 – 5), the consolidation RPTD of 
veliparib will be 120 mg BID + carboplatin AUC 6 + paclitaxel 200 mg/m2 for up to two 21-day cycles.  
The consolidation dose of veliparib in Cohort 6 will be 240 mg BID + carboplatin AUC 6 + paclitaxel 
200 mg/m2 for up to two 21-day cycles.  
Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new dosing cohort is 
opened or until the recommended Phase 2 dose is identified.  A minimum of 3 subjects will be enrolled in 
each cohort.  Additional eligible subjects may be enrolled at the current dose level at the discretion of the 
Investigators and the AbbVie Medical Monitor.  From each cohort, subjects will be entered into the DLT 
assessment group of the intended cohort size in order of treatment.  For Cohorts 1 – 5, subjects 
considered evaluable for DLTs will be those that receive treatment through 1 cycle of CRT or have AEs 
meeting DLT criteria.  For Cohort 6, subjects considered evaluable for DLTs will be those that receive 
treatment through 1 cycle of consolidation chemotherapy.  If a subject in the DLT assessment group 
becomes unevaluable, the subject will be replaced by the next-treated subject in the cohort.  The DLT 
period for each subject participating in Cohorts 1 – 5 will be from start of veliparib dosing through 
28 days following completion of CRT or until consolidation chemotherapy is initiated.  The DLT period 
for each subject participating in Cohort 6, will be from the start of Cycle 1 of the consolidation 
chemotherapy through the start of the Cycle 2 of the consolidation therapy or treatment discontinuation.  
The DLT period for all subjects at each dose level will end upon initiation of next dose level.
Dose limiting toxicities are the following events that are considered by the investigator group to be 
related to treatment:
1.
Radiation induced Grade 3 or greater cardiac toxicity (e.g., myocarditis, pericarditis, heart failure, 
ventricular dysfunction, myocardial infarction). 
2.
Radiation induced myelopathy/myelitis (does not include L'Hermitte's syndrome).
3.
Radiation-related pneumonitis resulting in delay in radiotherapy, chemotherapy (CRT or 
consolidation) or veliparib of more than 3 weeks or early discontinuation of RT (total dose < 50 Gy).
4.
G4 or greater esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment 
interruption of > 7 days despite medical management.
5.
G2 or greater seizure.
6.
Grade 4 or greater neutropenia for > 7 days or neutropenic fever (defined as ANC < 500 and a 
temperature of 38.5°C or above).
7.
Grade 4 or greater thrombocytopenia.
8.
Grade 4 diarrhea or nausea/vomiting despite appropriate antiemetic therapy lasting > 48 hours.
9.
Any other toxicity resulting in delay in radiotherapy, chemotherapy, or veliparib of more than 
14 days or early discontinuation of RT (total dose < 50 Gy).


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M14-360 Protocol Amendment 4
143
Methodology (Continued):
10. All other non-hematologic toxicities of Grade 3 or greater, with the following exceptions:
a.
Anorexia
b.
Fatigue
c.
Grade 3 infection
d.
Grade 3 AST/ALT elevations ≤ 7 days
e.
Infusion reactions.  Patients with Grade 3 or worse infusion reactions will be removed from 
study and replaced and will not be considered evaluable for DLT
f.
Grade 3 or 4 lymphopenia
g.
Grade 3 or 4 electrolyte abnormalities that are corrected to Grade 2 or less in less than 48 hours
For Cohort 6, if 3 or fewer subjects were able to take Cycle 2 of consolidation chemotherapy, the reason 
of dose reduction and treatment discontinuation will be reviewed as part of consideration to determine 
MTD/RPTD of veliparib for the consolidation phase.
Following the dose escalation portion of the trial, the RPTD will be determined by the sponsor, and at the 
discretion of the sponsor, the Phase 2 portion of the study will begin with patient randomization in a 
1:1:1 ratio to the treatment arms as follows:
A.
Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/veliparib
B.
Concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/placebo
C.
Concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation 
paclitaxel/carboplatin/placebo
Subject randomization will be stratified by tumor volume (≤ 90 versus > 90 cm3) and smoking history 
(current smoker versus former smoker versus never smoked).  Screening procedures, QoL assessment, 
and baseline radiographic tumor assessments will be performed within 28 days prior to randomization.
Concurrent chemoradiotherapy (CRT) will consist of radiotherapy (RT) using either 3D conformal RT or 
IMRT plus paclitaxel, (45 mg/m2 as a 60 minute infusion), immediately followed by carboplatin, 
(AUC 2 mg/mL/min as a 30 minute infusion) weekly beginning on Day 1 of radiotherapy.  Veliparib (or 
placebo), will be administered continuously beginning 3 days prior to RT through one day after RT 
completion.
Consolidation chemotherapy will begin no more than 8 weeks following RT.  Subjects who require 
> 8 weeks to recover from toxicities resulting from CRT should not receive consolidation chemotherapy.  
Consolidation chemotherapy will consist of paclitaxel, (200 mg/m2 as a 3 hour infusion, immediately 
followed by carboplatin, AUC 6 mg/mL/min as a 30 minute infusion) on Day 1 of each 21-day cycle for 
up to 2 cycles.  Veliparib (or Placebo in the Phase 2 portion), 120 mg (Cohorts 1 – 5) or 240 mg 
(Cohort 6) BID, will begin on Day –2 (2 days prior to the start of paclitaxel/carboplatin infusion) and will 
continue through Day 5 of each 21-day cycle.  
Subjects who experience toxicities due to carboplatin, paclitaxel, RT, or veliparib/placebo may require a 
delay in the dosing schedule or a dose modification.


Veliparib
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Methodology (Continued):
Radiographic tumor assessments will be conducted at baseline, prior to consolidation chemotherapy, at 
24 weeks after start of treatment, every 8 weeks until one year after beginning therapy, then every 
12 weeks.  Beginning 12 weeks after randomization, progression will be determined based on Response 
Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.  Progression prior to that time will be 
determined by the Investigator.  A QoL assessment as measured by the EORTC QLQ-C15-PAL and the 
companion symptom module EORTC QLQ-LC13 will be performed at Screening, prior to consolidation 
chemotherapy, at 24 weeks after start of treatment, every 8 weeks until one year after beginning therapy 
and at the final visit.
After completion of protocol therapy, subjects will be observed without further therapy until progression.  
The visit at which an investigator identifies disease progression or at which a subject meets other criteria 
for study discontinuation will be considered the final visit.  All subjects with a final visit < 30 days after 
the last dose of drug will have one Follow-Up Visit approximately 30 days after the Final Visit.
If a subject is discontinued from the study with an ongoing adverse event or an unresolved clinically 
significant laboratory result, the site will attempt to provide follow-up until a satisfactory clinical 
resolution of the laboratory results or adverse event is achieved.
To ensure subject safety, an internal data monitoring committee (DMC) will review un-blinded safety 
data when approximately 45 subjects in the Phase 2 portion of the study have completed CRT, reached an 
event of disease progression or death, or discontinued the study.
Diagnosis:  Stage III NSCLC
Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion (Phase 1 and Randomized Phase 2):
!
Subject must be ≥ 18 years of age;
!
Subject must have histologically or cytologically confirmed Stage III NSCLC.  When pleural fluid 
is visible on the CT scan or on a chest x-ray, a thoracentesis is required to confirm that the pleural 
fluid is serous AND cytologically negative.  Effusions that are minimal (i.e., not visible on chest 
x-ray) or that are too small to safely tap are exempted from the requirement for thoracentesis. 
!
Subjects in the randomized portion of the study must have measurable disease per RECIST 
version 1.1 criteria;
!
Subject must consent to provide archived tissue or cytology sample of NSCLC lesion for analysis;
!
Subjects must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) 
< 35%;
!
Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 – 1;


Veliparib
M14-360 Protocol Amendment 4
145
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Inclusion (Continued):
!
Subject must have adequate hematologic, renal, hepatic, and lung function as follows: 
o
Bone marrow:  Absolute Neutrophil count (ANC) ≥ 1,500/μL; Platelets ≥ 100,000/mm3; 
Hemoglobin ≥ 9.0 g/dL (without transfusion);
o
Renal function:  calculated creatinine clearance ≥ 50 mL/min by the Cockcroft-Gault formula;
o
Hepatic function and enzymes:  aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) ≤ 2.5 × the upper limit of normal (ULN) of institution's normal range; 
Bilirubin ≤ 1.5 × ULN; subjects with Gilbert's syndrome may have a bilirubin ≥ 1.5 × ULN of 
central laboratory normal range; 
o
Pulmonary function tests (PFTs) including FEV1 within 12 weeks prior to randomization; for 
FEV1, the best value obtained pre- or post-bronchodilator must be ≥ 1.2 liters/second and/or 
≥50% predicted.
!
Female subjects of childbearing potential (i.e., those who are not postmenopausal for at least 1 year 
or surgically sterile by bilateral tubal ligation, bilateral oophorectomy or hysterectomy) and their 
male partner should practice at least one of the methods of birth control listed below for at least 
6 months after treatment with chemotherapy.  Male subjects and their female partners of 
childbearing potential should practice at least one of the methods of birth control listed below for 
at least 6 months after treatment with chemotherapy:
o
Total abstinence from sexual intercourse (if it is the subject's preferred and usual lifestyle; 
beginning a minimum one complete menstrual cycle prior to study drug administration and to 
extend 6 months after treatment);
o
Vasectomized subject or partner(s), vasectomy (males);
o
Intrauterine device (females);
o
Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with 
spermicidal jellies or creams; both males and females);
o
Hormonal contraceptives (oral, parenteral or transdermal) for at least 90 days prior to study 
drug administration (females).  If hormonal contraceptives are used, the subject and her 
partner should also use a single barrier method.
o
Subject must voluntarily sign and date an informed consent, approved by an Independent 
Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of and 
Screening for study-specific procedures.


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146
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Exclusion:  
!
Subject with prior chemotherapy or radiotherapy for current NSCLC; subjects curatively treated 
for past early stage NSCLC greater than 3 years ago may be included;
!
Subject with prior exposure to PARP inhibitors;
!
Subjects with known hypersensitivity to carboplatin, paclitaxel, or formulations containing 
polyethoxylated castor oil (Cremophor);
!
Subject with prior mediastinal or thoracic radiotherapy.  Prior tangential RT to prior breast 
cancer is acceptable;
!
Subject with major surgery in the 4 weeks prior to randomization (VATS and/or 
mediastinoscopy is not considered major surgery);
!
Subject with a previous or concurrent malignancy except for treated basal cell or squamous cell 
skin cancer, in situ cervical cancer, or other cancer for which the patient received potentially 
curative treatment and has been disease-free for 3 years or is considered cured by the 
investigator if has been disease-free for less than 3 years;
!
Any medical condition, which in the opinion of the study investigator, places the subject at an 
unacceptably high risk for toxicities, or any subject circumstance that prohibits trial participation 
according to local law;
!
Subject is pregnant or lactating;
!
Subject with sensory peripheral neuropathy of ≥ Grade 2 at baseline;
!
Subject is unable to swallow medication;
!
Subjects with prior history of seizure within the prior 12 months.
Investigational Product:
Veliparib (ABT-888) or Placebo
Dose(s):
60 – 240 mg BID (concurrent chemoradiotherapy); 
120 – 240 mg BID (consolidation)
Mode of Administration:
Oral
Reference Therapy:
Carboplatin 
Dose(s):
AUC 2 mg/mL/min (concurrent chemoradiotherapy); 
AUC 6 mg/mL/min (consolidation)
Mode of Administration:
Intravenous
Reference Therapy:
Paclitaxel
Dose(s):
45 mg/m2 (concurrent chemoradiotherapy);
200 mg/m2 (consolidation)
Mode of Administration:
Intravenous
Duration of Treatment:  
Subjects without clinical progression of disease and with tolerable side effects should continue to receive 
treatment until completion of all prescribed cycles (chemoradiotherapy plus 2 cycles of consolidation 
chemotherapy).


Veliparib
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147
Criteria for Evaluation:
Efficacy:
Progression-free survival (PFS) will be derived according to radiographic progression per RECIST 
version 1.1 (beginning with the second scan after completion of CRT) or death.  Radiographic tumor 
assessments for response will be conducted at baseline, prior to consolidation chemotherapy, at 24 weeks 
after start of treatment, every 8 weeks until one year after beginning therapy, then every 12 weeks until 
radiographic progression or death.  Subjects who require additional therapy, withdraw consent, or are lost 
to follow-up prior to radiographic progression will be censored at that time for the analysis of PFS.
Overall survival (OS) will be determined by the Investigator until radiographic progression.  After 
radiographic progression, survival information will be collected via the electronic CRF at 8-week 
intervals (or as requested by sponsor to support data analysis).
Objective response rate (ORR), and duration of overall response (DOR) will be derived per RECIST 
version 1.1.  Radiographic tumor assessments for response will be conducted at baseline, prior to 
consolidation chemotherapy, at 24 weeks after start of treatment, every 8 weeks until one year after 
beginning therapy, then every 12 weeks until radiographic progression or death.  Subjects who require 
additional therapy, withdraw consent, or are lost to follow-up prior to radiographic progression will be 
censored at that time for the analysis of DOR.
ECOG performance status will be determined by the Investigator at each assessment.  A quality of life 
assessment as measured by the EORTC QLQ-C15-PAL and the companion symptom module EORTC 
QLQ-LC13 will be performed at screening, prior to consolidation chemotherapy, at 24 weeks after start 
of treatment, every 8 weeks until one year after beginning therapy and at the final visit.
Pharmacokinetic:
Blood samples for veliparib assay will be collected for the determination of pharmacokinetic parameters 
of veliparib such as apparent oral clearance (CL/F) and volume of distribution (V/F).
Pharmacodynamic:
Research to find biomarkers that may serve as surrogates for clinical endpoints in future veliparib studies 
or that may be predictive of veliparib activity will be conducted.  Serum, plasma, blood and archived 
tissue samples will be collected at designated time points throughout the study.  Study-specific core 
biopsies are requested but are not required.
Safety:
Adverse events, laboratory profiles, physical examinations and vital signs will be assessed throughout the 
study.  Results will be tabulated for each subject and summary statistics will be computed for each 
sampling time and each parameter.


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Statistical Methods:
The following efficacy endpoint will be analyzed using data obtained from subjects in Phase 1:
Objective Response Rate (ORR)
The proportion of subjects with objective response as assessed by the investigator using RECIST 
version 1.1 will be calculated for all dosed subjects. 
The following efficacy endpoints will be analyzed using data obtained from subjects in Phase 2:
Progression-Free survival (PFS)
Progression-Free Survival will be defined as the number of days from the date of randomization to the 
date of earliest radiographic disease progression or death.  All radiographic disease progression will be 
included regardless whether the event occurred while the subject was taking study drug or had previously 
discontinued study drug.  If the subject does not experience radiographic disease progression or death, 
then the data will be censored at the date of the last disease assessment.
Overall Survival (OS)
Overall survival will be defined as the number of days from the date of randomization to the date of 
death.  For subjects who did not die, their data will be censored at the date of last study visit or the last 
known date to be alive, whichever is later.
Objective Response Rate (ORR) 
The proportion of subjects with objective response as assessed by the investigator using RECIST 
version 1.1 will be evaluated for randomized subjects. 
Duration of Overall Response (DOR)
Duration of overall response will be defined as the number of days from the date of first response (CR or 
PR) to the earliest documentation of radiographic progressive disease or death due to disease progression.  
If a subject is still responding, then the subject's data will be censored at the date of the subject's last 
available disease assessment.  For subjects who never experience response, the subject's data will not be 
included in the analysis.
Quality of life (QoL) Measures
Changes and/or percent changes from baseline will be summarized using descriptive statistics for each 
scheduled post-baseline visit and for the Final Visit for quality of life measures using the EORTC 
QLQ-C15-PAL and EORTC QLQ-LC13 questionnaires.  The QoL will be used as an exploratory 
endpoint and not tested against pre-specified hypothesis.
Performance Status
Changes and/or percent changes from baseline will be summarized using descriptive statistics for each 
scheduled post-baseline visit and for the Final Visit for ECOG performance status.  Post-baseline 
measurements more than 30 days after the last dose of study drug will not be included.  Subjects that do 
not have a baseline measurement or do not have any post-baseline measurements will not be included.
Efficacy Analysis:
The primary Phase 2 efficacy analysis will test if concurrent paclitaxel/carboplatin/radiotherapy/veliparib 
followed by consolidation paclitaxel/carboplatin/veliparib (Arm A) will improve PFS versus concurrent 
paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo 
(Arm C).


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Statistical Methods (Continued):
Efficacy Analysis (Continued):
The secondary Phase 2 efficacy analyses will test (in the following order):  
1) if concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation 
paclitaxel/carboplatin/placebo (Arm B) results in improved Progression-Free survival (PFS) versus 
Arm C; 
2a) if Arm A or 
2b) if Arm B results in improved overall survival (OS) versus Arm C; 
3a) if Arm A or 
3b) if Arm B results in improved overall response rate (ORR) versus Arm C;
4a) if Arm A or 
4b) if Arm B results in improved duration of overall response (DOR) versus Arm C.
Sample Size:
Assuming a hazard ratio of 0.6 for Arm A (Concurrent paclitaxel/carboplatin/radiotherapy/veliparib 
followed by consolidation paclitaxel/carboplatin/veliparib) versus Arm C (Concurrent 
paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo), a 
total of 71 PFS events in Arm A and Arm C combined will provide an expected 95% confidence interval 
of 0.38 to 0.96 for the estimated hazard ratio.  Assuming a hazard ratio of 0.75 for Arm B (Concurrent 
paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/placebo) 
versus Arm C, a total of 107 PFS events will be observed across all three arms at the time when 71 PFS 
events are observed for Arm A and Arm C combined.  A total of approximately 156 subjects (52 subjects 
per treatment arm) will be enrolled into the Phase 2 portion of study to obtain the 107 PFS events.
Section 1.3  List of Abbreviations and Definition of Terms
Subsection Abbreviations:
Add:
DLCO
Diffusing Capacity of the Lung for Carbon Monoxide
Section 4.0  Study Objective
First paragraph previously read:
The primary objectives of the study are to establish the recommended Phase 2 dose 
(RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based 
chemoradiotherapy (CRT) and to assess whether the addition of oral veliparib versus 
placebo to paclitaxel/carboplatin-based chemoradiotherapy with consolidation 
paclitaxel/carboplatin will improve progression-free survival (PFS) in patients with 
Stage III non-small cell lung cancer (NSCLC).


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Has been changed to read:
The primary objectives of the study are to establish the recommended Phase 2 dose 
(RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based 
chemoradiotherapy (CRT) and paclitaxel/carboplatin-based consolidation 
chemoradiotherapy and to assess whether the addition of oral veliparib versus placebo to 
paclitaxel/carboplatin-based chemoradiotherapy with consolidation paclitaxel/carboplatin 
will improve progression-free survival (PFS) in patients with Stage III non-small cell lung 
cancer (NSCLC).
Section 5.1  Overall Study Design and Plan:  Description
Previously read:
This two-phase study consists of 1) dose-escalation of veliparib to determine an RPTD for 
combination with concurrent paclitaxel/carboplatin-based CRT; and 2) a randomized, 
double-blinded study to determine whether veliparib improves outcome relative to 
placebo when added to paclitaxel/carboplatin based CRT followed by consolidation 
paclitaxel/carboplatin in subjects with previously untreated Stage III NSCLC.
Has been changed to read:
This two-phase study consists of 1) dose-escalation of veliparib to determine an RPTD for 
combination with concurrent paclitaxel/carboplatin-based CRT and paclitaxel/carboplatin-
based consolidation chemoradiotherapy; and 2) a randomized, double-blinded study to 
determine whether veliparib improves outcome relative to placebo when added to 
paclitaxel/carboplatin based CRT followed by consolidation paclitaxel/carboplatin in 
subjects with previously untreated Stage III NSCLC.
Section 5.2  Selection of Study Population
First paragraph, first sentence previously read:
The study was designed to enroll approximately 186 subjects with Stage III NSCLC 
(approximately 30 in the dose escalation portion and approximately 156 in the 
randomized portion) at approximately 50 – 75 study centers to meet scientific and 


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regulatory objectives without enrolling an undue number of subjects in alignment with 
ethical considerations.  
Has been changed to read:
The study was designed to enroll approximately 206 subjects with Stage III NSCLC 
(approximately 50 in the dose escalation portion and approximately 156 in the 
randomized portion) at approximately 50 – 75 study centers to meet scientific and 
regulatory objectives without enrolling an undue number of subjects in alignment with 
ethical considerations.  
Table 1.  Dose Escalation
Previously read:
Dose Level
Number of Subjects
Veliparib (mg)
1
3 – 6
60
2
3 – 6
80
3
3 – 6
120
4
3 – 6
200
5
3 – 6
240
–1
0 – 6
40
Has been changed to read:
Dose Escalation in the Concurrent Chemoradiotherapy
Cohort
Dose Level
Number of Subjects
Veliparib (mg)
1
1
3 – 6
60
2
2
3 – 6
80
3
3
3 – 6
120
4
4
3 – 6
200
5
5
3 – 6
240
–1
0 – 6
40


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Dose Escalation in the Consolidation Chemotherapy
Cohort
Dose Level
Number of Subjects
Veliparib (mg)
1 – 5
3 – 6
120
6
3 – 6
240
Section 5.2  Selection of Study Population
Subsection Dose Escalation Portion (Phase 1)
Third paragraph previously read:
Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new 
dosing cohort is opened or until the RPTD is identified.  The DLT period for each subject 
will be from the start of veliparib dosing through 28 days following completion of RT or 
until consolidation chemotherapy is initiated, and the DLT period for all subjects at each 
dose level will end upon initiation of the next dose level.  The consolidation dose of 
veliparib will be 120 mg BID + carboplatin (AUC 6 mg/mL/min) + paclitaxel 
(200 mg/m2) for up to two 21-day cycles.
Has been changed to read:
Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new 
dosing cohort is opened or until the RPTD is identified.  During CRT dose escalation, the 
DLT period for each subject will be from the start of veliparib dosing through 28 days 
following completion of RT or until consolidation chemotherapy is initiated, and the DLT 
period for all subjects at each dose level will end upon initiation of the next dose level.  
CRT dose escalation will occur with a consolidation dose of veliparib of 120 mg BID + 
carboplatin (AUC 6 mg/mL/min) + paclitaxel (200 mg/m2) for up to two 21-day cycles.  
Once the concurrent CRT RPTD is identified, an additional cohort will be enrolled to 
explore the tolerability of a consolidation dose of veliparib at 240 mg BID + carboplatin 
(AUC 6 mg/mL/min) + paclitaxel (200 mg/m2) for up to two 21-day cycles.  
Subjects overenrolled in Cohort 5 will be allowed to roll over into Cohort 6 as long as 
they have not started the consolidation phase, and at the discretion of the Investigators and 
the AbbVie Medical Monitor.


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For Cohort 6, the DLT period will be 21 days from start of consolidation chemotherapy or 
until the start of Cycle 2 consolidation therapy. 
For this cohort, if 3 or less subjects were able to take Cycle 2 of consolidation 
chemotherapy, the reason of dose reduction and treatment discontinuation will be 
reviewed as part of consideration to determine MTD/RPTD of veliparib for the 
consolidation phase.
Section 5.2.1  Inclusion Criteria
Add:  new Criterion 4
Subject must consent to provide archived tissue or cytology sample of NSCLC lesion for 
analysis;
Section 5.2.1  Inclusion Criteria
Subsection Rationale for Inclusion Criteria
Previously read:
1 – 6
To select the appropriate subject population with sufficient disease severity for 
evaluation
7
The impact of veliparib plus paclitaxel/carboplatin-based chemoradiotherapy 
followed by paclitaxel/carboplatin consolidation on the unborn fetus is 
unknown; therefore, these criteria ensure that adequate precautions are taken 
to avoid pregnancy
8
In accordance with harmonized Good Clinical Practice (GCP)
Has been changed to read:
1 – 7
To select the appropriate subject population with sufficient disease severity for 
evaluation
8
The impact of veliparib plus paclitaxel/carboplatin-based chemoradiotherapy 
followed by paclitaxel/carboplatin consolidation on the unborn fetus is 
unknown; therefore, these criteria ensure that adequate precautions are taken 
to avoid pregnancy
9
In accordance with harmonized Good Clinical Practice (GCP)


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Table 2.  Study Activities (Phase 1 and 2)
Activity "PFTm" and "Chemistry/Hematologyp" previously read:
Activity 
Screeninga
Concurrent 
(Chemoradiotherapy)
Post CRT Visitc
Consolidationd
Post-Treatment 
Visite
Final Visitf
30-Day FU Visitg
Survival Period
Wk 
1
Day 
–3
Wk
1 – 3 
Day 
1
Wk 
4 
Day 
–3
Wk 
4 – 9b
Day 
1
Wk 
7 
Day
–3b
Cycle
1
Day –2
Cycle 
1 
Day 1
Cycle 
2 
Day 1
PFTm
X
Chemistry/Hematologyp
X
X
X
X
X
X
X
Has been changed to read:
Activity 
Screeninga
Concurrent 
(Chemoradiotherapy)
Post CRT Visitc
Consolidationd
Post-Treatment 
Visite
Final Visitf
30-Day FU Visitg
Survival Period
Wk 
1
Day 
–3
Wk
1 – 3 
Day 
1
Wk 
4 
Day 
–3
Wk 
4 – 9b
Day 
1
Wk 
7 
Day
–3b
Cycle
1
Day –2
Cycle 
1 
Day 1
Cycle 
2 
Day 1
PFTm
X
X
Chemistry/Hematologyp
X
X
X
X
X
X
X
X
Table 2.  Study Activities (Phase 1 and 2)
Table note "m."
Add:  new second and third sentence
PFT will be performed at 12 months post start of radiation therapy.  If subject is no longer 
coming in for Post-Treatment Visits, every effort should be made to still collect the PFT 
at this 12 month timepoint.
Table 2.  Study Activities (Phase 1 and 2)
Table note "p."
Add:  new last sentence
Blood Draw (hemoglobin only) to be collected in the Post Treatment visit at 12 months 
post start of radiation therapy.


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Table 3.  Schedule of Pharmacogenetic and Pharmacodynamic Assessments
Procedure "Archived Tissue Sample Collection* (optional)" previously read:
Archived Tissue Sample Collection* (optional)
Has been changed to read:
Archived Tissue Sample Collection
Table 3.  Schedule of Pharmacogenetic and Pharmacodynamic Assessments
Table note "c."
Add:  new second, third and fourth sentence
Subjects must consent to provide available archival tissue for analysis.  It is preferred to 
send FFPE blocks, however slides prepared by the local pathology laboratory are 
acceptable and should be prepared as described in the study specific laboratory manual.  If 
there is not enough tissue to provide the number of slides specified in the laboratory 
manual, sites should provide as many slides as possible with the available tissue.
Section 5.3.1.1  Study Procedures
Subsection Informed Consent
First paragraph, third and fourth sentence previously read:
Archived tissue collection is optional.  Subjects must consent to provide available archival 
tissue for analysis.
Has been changed to read:
Archived tissue collection is optional for all subjects participating in Cohort 1 – 5.  
Subjects participating in Cohort 6 must consent to provide archived tissue or cytology 
sample for analysis.


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Section 5.3.1.1  Study Procedures
Subsection Pulmonary Function Test Procedure (PFT)
Add:  new subsection title and text
Pulmonary Function Test procedure (PFT)
The PFT procedure will be performed per Table 2.  The Pulmonary function test should 
include spirometry with FEV1 and DLCO documentation.  Hemoglobin lab assessment 
will be needed to generate a DLCO (Hb).
Section 5.3.1.3  Collection and Handling of Pharmacodynamic Variables
Subsection Archived Tissue Collection
First sentence previously read:
If available, fixed samples from most recent biopsy should be collected from subjects who 
have consented, while subject is active on study.  
Has been changed to read:
If available, fixed samples from most recent biopsy should be collected from subjects 
participating in Cohort 1 – 5 who have consented, while subject is active on study.  
Section 5.3.1.3  Collection and Handling of Pharmacodynamic Variables
Subsection Archived Tissue Collection
Add:  new third and fourth sentence
Subjects participating in Cohort 6 must consent to provide available archived tumor for 
analysis.  It is recognized that the availability of the samples suitable for analysis may not 
be known at the time of consent for all subjects.
Section 5.3.7  Pharmacodynamic Variables
Second paragraph, second sentence previously read:
These characterizations may be included, but are not limited, characterization of gene 
methylation/mutational status or copy number changes of genes, particularly those 
involved in DNA repair pathways.  


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Has been changed to read:
These characterizations may be included, but are not limited, characterization of gene 
expression, methylation/mutational status or copy number changes of genes, particularly 
those involved in DNA repair pathways.  
Section 5.5.1  Treatments Administered
Subsection Concurrent Chemoradiotherapy
Delete:  last paragraph
AbbVie will review available safety data from all subjects in the dose escalation portion 
of the study and determine the recommended Phase 2 dose (RPTD) for veliparib during 
chemoradiotherapy.  Subjects in the randomized portion of the study will receive the 
veliparib RPTD or placebo during chemoradiotherapy.
Section 5.5.1  Treatments Administered
Subsection Consolidation Chemotherapy
First sentence previously read:
No more than 8 weeks after completion of concurrent chemoradiotherapy, 
veliparib/placebo 120 mg BID will be administered beginning 2 days prior to the start of 
paclitaxel/carboplatin infusion and will continue through Day 5 of each 21-day cycle.  
Has been changed to read:
No more than 8 weeks after completion of concurrent chemoradiotherapy, 
veliparib/placebo 120 mg or 240 mg BID will be administered beginning 2 days prior to 
the start of paclitaxel/carboplatin infusion and will continue through Day 5 of each 21-day 
cycle.  


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Section 5.5.1  Treatments Administered
Subsection Phase 2 Treatment Regimen:  RPTD or Placebo
Add:  new subsection title and text
Phase 2 Treatment Regimen:  RPTD or Placebo
AbbVie will review available safety data from all subjects in the dose escalation portion 
of the study and determine the CRT and consolidation RPTDs.  Subjects in the 
randomized portion of the study will receive the veliparib RPTD or placebo during CRT 
and consolidation.
Section 5.6.4  Selection of Doses in the Study
Previously read:
The doses of standard therapy (radiotherapy, carboplatin, paclitaxel) are guideline 
recommended or based on randomized studies of subjects with advanced NSCLC.3  The 
dose escalation portion of this study will determine the appropriate dose of veliparib with 
standard-dose concurrent chemoradiotherapy by the 3 + 3 cohort design commonly used 
for determining tolerability.  During consolidation therapy, doses of standard therapy and 
the dose of investigational agent (veliparib) in this study are identical to those used in a 
randomized, double-blind placebo controlled Phase 2 study of carboplatin and paclitaxel 
± veliparib for advanced metastatic NSCLC.  As described in Section 3.0, preliminary 
data from this study show the combination is well-tolerated, showed delivery of 
carboplatin and paclitaxel were not substantially compromised, and suggested improved 
efficacy in subjects who received veliparib.
The maximum dose of veliparib/placebo for any subject in this study is 240 mg BID 
continuously during chemoradiotherapy followed by 120 mg BID for 7 of 21 days over 
2 cycles.
Has been changed to read:
The doses of standard therapy (radiotherapy, carboplatin, paclitaxel) are guideline 
recommended or based on randomized studies of subjects with advanced NSCLC.3  The 
dose escalation portion of this study will determine the appropriate dose of veliparib with 


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standard-dose concurrent chemoradiotherapy and consolidation chemotherapy by a 3 + 3 
cohort design.
Both 120 mg BID veliparib and 240 mg BID (or higher) have been used in Phase 2 and 
Phase 3 studies in combination with platinum doublet in different patient population.  In 
Cohorts 1 – 5, the 120 mg BID dose of investigational agent (veliparib) in the 
consolidation portion was selected based on a randomized, double-blind placebo 
controlled Phase 2 study of carboplatin and paclitaxel ± veliparib for advanced metastatic 
NSCLC, and to ensure the capability to escalate veliparib dose in combination with 
Chemo-RT.  
Once the CRT RPTD is determined, a 6th cohort will be enrolled with subjects at 240 mg 
BID dose in the consolidation portion as indicated in Table 1.  The dose selection of 
240 mg BID was supported by safety data in Phase 1 studies with veliparib in 
combination with carboplatin/paclitaxel, an ongoing Phase 2 study of 240 mg BID of 
veliparib in combination of carboplatin/etopside for extended stage of small cell lung 
cancer, and a Phase 3 study of 300 mg BID veliparib in combination of 
carboplatin/paclitaxel in front line ovarian cancer patients.  As described in Section 3.0, 
preliminary data from this study show the combination is well-tolerated, showed delivery 
of carboplatin and paclitaxel were not substantially compromised, and suggested 
improved efficacy in subjects who received veliparib.
The maximum dose of veliparib/placebo for any subject in this study is 240 mg BID 
continuously during chemoradiotherapy followed by 240 mg BID for 7 of 21 days over 
2 cycles of consolidation chemotherapy.


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Section 6.6.3  Reporting Serious Adverse Events
"Primary Study Designated Physician:" previously read:
AbbVie
1 North Waukegan Road
North Chicago, IL  60064
Office:
Fax:
Mobile:
Email:
Has been changed to read:
AbbVie
1 North Waukegan Road
North Chicago, IL 60064
Office:
Fax:
Mobile:
Email:
Section 6.8.1  Dose Limiting Toxicities
First paragraph, seventh sentence previously read:
The DLT period for each subject will be from start of veliparib dosing through 28 days 
following completion of CRT or until consolidation chemotherapy is initiated, and the 
DLT period for all patients at each dose level will end upon initiation of next dose level.  


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Has been changed to read:
The DLT period for each subject in the concurrent CRT dose escalation will be from start 
of veliparib dosing through 28 days following completion of CRT or until consolidation 
chemotherapy is initiated, and the DLT period for all patients at each dose level will end 
upon initiation of next dose level.  The DLT period for each subject during consolidation 
chemotherapy dose (Cohort 6), will be 21 days from start of consolidation or until the 
start of Cycle 2 of the consolidation therapy or treatment discontinuation.   
Section 6.8.3  Determination of the RPTD
First and second sentence previously read:
AbbVie will review available safety data from all subjects in the dose escalation portion 
of the study and determine the RPTD for veliparib during chemoradiotherapy.  Subjects in 
the randomized portion of the study will receive the veliparib RPTD or placebo during 
chemoradiotherapy.  
Has been changed to read:
AbbVie will review available safety data from all subjects in the dose escalation portion 
of the study and determine the RPTD for veliparib during chemoradiotherapy and 
consolidation chemotherapy.  Subjects in the randomized portion of the study will receive 
the veliparib CRT RPTD or placebo during chemoradiotherapy and the veliparib 
consolidation RPTD or placebo during consolidation.  
Table 10.  Suggested Guidelines for Veliparib + Paclitaxel/Carboplatin Independent 
Dose Reduction
Previously read:
Dose Level
Carboplatin
Paclitaxel
Veliparib/Placebo
Starting Dose Level
AUC 6
200 mg/m2
120 mg BID
Dose Level –1
AUC 5
175 mg/m2
80 mg BID
Dose Level –2
AUC 4
150 mg/m2
40 mg BID


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Has been changed to read:
Dose Level
Carboplatin
Paclitaxel
Veliparib/Placebo
Starting Dose Level (for 
subjects participating in 
Cohort 6)
AUC 6
200 mg/m2
240 mg BID
Starting Dose Level –1
120 mg BID
Dose Level –2
AUC 5
175 mg/m2
80 mg BID
Dose Level –3
AUC 4
150 mg/m2
60 mg BID
Section 7.0  Protocol Deviations
"Medical Monitor:" previously read:
AbbVie
1 North Waukegan Road
North Chicago, IL  60064
Office: 
Fax:
Cell:
Email:
Has been changed to read:
AbbVie
1 North Waukegan Road
North Chicago, IL 60064
Office:
Fax:
Mobile:
Email:


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Section 7.0  Protocol Deviations
Delete:  "Clinical Monitor"
Clinical Monitor
1 North Waukegan Road
North Chicago, IL  60064
Office: 
Fax: 
Cell: 
Email:
Section 8.2  Determination of Sample Size
First paragraph previously read:
Approximately 30 subjects will be enrolled in the dose escalation portion of the study.
Has been changed to read:
Approximately 50 subjects will be enrolled in the dose escalation portion of the study.
Section 9.3  Subject Information and Consent
Last paragraph previously read:
Archived tissue analysis will only be performed if the subject has voluntarily consented 
for tissue sampling on the informed consent, approved by an IRB/IEC, after the nature of 
the testing has been explained and the subject has had an opportunity to ask questions.  If 
the subject does not consent to the archived tissue analysis, it will not impact the subject's 
participation in the study.


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Has been changed to read:
For subjects participating in Cohort 1 – 5, archived tissue analysis will only be performed 
if the subject has voluntarily consented for tissue sampling on the informed consent, 
approved by an IRB/IEC, after the nature of the testing has been explained and the subject 
has had an opportunity to ask questions.  If the subject does not consent to the archived 
tissue analysis, it will not impact the subject's participation in the study.  Subjects in 
Cohort 6 must consent to provide available archival tumor for analysis.  It is recognized 
that the availability of the samples suitable for analysis may not be known at the time of 
consent for all subjects.
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Clinical
GDSM
Clinical
Clinical
Statistics
Clinical Pharmacology & 
Pharmacometrics
Bioanalysis
Biometrics


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Has been changed to read:
Name
Title
Functional Area
Clinical
GDSM
Clinical
Clinical
Statistics
Clinical Pharmacology & 
Pharmacometrics
Bioanalysis
Biometrics