Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Adults Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT02264990
Collaborator
(none)
595
140
2
64.7
4.3
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of veliparib plus carboplatin and paclitaxel versus the Investigator's choice of standard chemotherapy in adults with metastatic or advanced non-squamous non-small cell lung cancer.

Study Design

Study Type:
Interventional
Actual Enrollment :
595 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-Label, Multicenter, Phase 3 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers
Actual Study Start Date :
Sep 30, 2014
Actual Primary Completion Date :
Nov 14, 2019
Actual Study Completion Date :
Feb 21, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Veliparib + Carboplatin + Paclitaxel

Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.

Drug: Paclitaxel
Administered by Intravenous infusion on Day 1 of each 21-day cycle

Drug: Carboplatin
Administered by Intravenous infusion on Day 1 of each 21-day cycle

Drug: Veliparib
Oral capsule, administered twice daily for 7 days in each 21-day cycle
Other Names:
  • ABT-888
  • Drug: Pemetrexed
    Administered by Intravenous infusion on Day 1 of each 21-day cycle
    Other Names:
  • Alimta
  • Active Comparator: Investigator's Choice Chemotherapy

    Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.

    Drug: Paclitaxel
    Administered by Intravenous infusion on Day 1 of each 21-day cycle

    Drug: Carboplatin
    Administered by Intravenous infusion on Day 1 of each 21-day cycle

    Drug: Cisplatin
    Administered by Intravenous infusion on Day 1 of each 21-day cycle

    Drug: Pemetrexed
    Administered by Intravenous infusion on Day 1 of each 21-day cycle
    Other Names:
  • Alimta
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup [From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.]

      Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup [From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.]

      Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death (all causes of mortality), whichever occurred first. PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cutoff date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.

    2. Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup [Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively.]

      Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed. CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.

    3. Overall Survival in All Participants [From randomization up to the data cut-off date of 15 July 2019; the median OS follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.]

      Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. OS was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.

    4. Progression Free Survival (PFS) in All Participants [From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.]

      Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per RECIST version 1.1 or death (all causes of mortality), whichever occurred first. PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.

    5. Objective Response Rate (ORR) in All Participants [Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively.]

      Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed. CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Subject must be ≥ 18 years of age with life expectancy > 12 weeks.

    • Subject must have cytologically or histologically confirmed advanced or metastatic non-squamous NSCLC and are current or former smokers.

    • Subject must have NSCLC that is not amenable to surgical resection or radiation with curative intent at time of screening.

    • Subject must have at least 1 unidimensional measurable NSCLC lesion on a computed tomography (CT) scan as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

    Exclusion Criteria:
    • Subject has a known hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor).

    • Subject has a known hypersensitivity to platinum compounds.

    • Subject has peripheral neuropathy ≥ grade 2.

    • Subject has squamous NSCLC, or an untreated known epidermal growth factor receptor (EGFR) mutation of exon 19 deletion or L858R mutation in exon 21, or a known anaplastic lymphoma kinase (ALK) gene rearrangement.

    • Subject has received prior cytotoxic chemotherapy or chemoradiotherapy for NSCLC.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clearview Cancer Institute /ID# 131434 Huntsville Alabama United States 35805
    2 University of South Alabama /ID# 131518 Mobile Alabama United States 36617
    3 Highlands Oncology Group /ID# 131250 Springdale Arkansas United States 72762
    4 CBCC Global Research, Inc. at /ID# 132709 Bakersfield California United States 93309
    5 California Cancer Assoc. R&E /ID# 131392 Encinitas California United States 92024
    6 California Cancer Assoc. R&E /ID# 131949 Encinitas California United States 92024
    7 LA Hem-Oncology Med Group /ID# 131639 Los Angeles California United States 90017
    8 St Jude Hospital dba St Joseph /ID# 132943 Santa Rosa California United States 95403
    9 Icri /Id# 132942 Whittier California United States 90603
    10 University of Florida - Archer /ID# 132408 Gainesville Florida United States 32610
    11 NorthShore University HealthSystem - Evanston Hospital /ID# 130200 Evanston Illinois United States 60201
    12 Goshen Center for Cancer Care /ID# 130216 Goshen Indiana United States 46526
    13 University of Louisville /ID# 130217 Louisville Kentucky United States 40202
    14 Cancer Center of Acadiana /ID# 133611 Lafayette Louisiana United States 70503
    15 Henry Ford Health System /ID# 130234 Detroit Michigan United States 48202
    16 Herbert Herman Cancer Center /ID# 130239 Lansing Michigan United States 48912
    17 Washington University-School of Medicine /ID# 131651 Saint Louis Missouri United States 63110
    18 MD Anderson Cancer Center at Cooper - Camden /ID# 131490 Camden New Jersey United States 08103
    19 Gabrail Cancer Center Research /ID# 130205 Canton Ohio United States 44718
    20 Univ Oklahoma HSC /ID# 132888 Oklahoma City Oklahoma United States 73104
    21 Albert Einstein Medical Center /ID# 134498 Philadelphia Pennsylvania United States 19141
    22 Allegheny General Hospital /ID# 134049 Pittsburgh Pennsylvania United States 15212
    23 The Jones Clinic, PC /ID# 130215 Germantown Tennessee United States 38138
    24 UT Southwestern Medical Center /ID# 130236 Dallas Texas United States 75390-7208
    25 Univ Texas HSC San Antonio /ID# 132972 San Antonio Texas United States 78229
    26 Coiba /Id# 132153 Berazategui, Buenos Aires Argentina 1884
    27 Centro Investigacion Pergamino /ID# 132152 Pergamino Argentina 2700
    28 Hospital Britanico /ID# 134874 Rosario, Santa FE Argentina 2000
    29 Instituto de Oncologia de Rosa /ID# 132150 Rosario, Santa FE Argentina 2000
    30 St George Hospital /ID# 132481 Kogarah New South Wales Australia 2217
    31 Southern Medical Day Care Ctr /ID# 132482 Wollongong New South Wales Australia 2500
    32 Flinders Centre for Innovation /ID# 134288 Bedford Park South Australia Australia 5042
    33 Royal Hobart Hospital /ID# 132477 Hobart Tasmania Australia 7000
    34 Qe Ii Hsc /Id# 133408 Halifax Nova Scotia Canada B3H 1V7
    35 Victoria Hospital /ID# 132161 London Ontario Canada N6A 4L6
    36 Windsor Regional Hospital /ID# 135989 Windsor Ontario Canada N9C 3Z4
    37 CSSS Alphonse-Desjardins, CHAU de Levis /ID# 132155 Quebec City Quebec Canada G6V 3Z1
    38 Krajska nemocnice Liberec a.s. /ID# 132694 Liberec Czechia 602 00
    39 Univ Hosp Ostrava-Poruba /ID# 132690 Ostrava Czechia 708 52
    40 Multiscan s.r.o. /ID# 132689 Pardubice Czechia 532 03
    41 Vseobecna Fakultni Nemocnice /ID# 135118 Prague Czechia 128 08
    42 Odense Universitets Hospital /ID# 131912 Odense C Syddanmark Denmark 5000
    43 Satakunnan Sairaanhoitopiiri /ID# 133632 Pori Finland 28500
    44 Vaasa Central Hospital /ID# 131930 Vaasa Finland 65130
    45 Charite-Univ. Berlin, Benjamin-Franklin /ID# 131927 Berlin Germany 12203
    46 Lungen Clinic Grosshansdorf /ID# 131928 Grosshansdorf Germany 22927
    47 Univ Klinik Eppendorf Hamburg /ID# 131926 Hamburg Germany 20246
    48 Klinik Loewenstein GmbH /ID# 131925 Löwenstein Germany 74245
    49 CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 133441 Miskolc Borsod-Abauj-Zemplen Hungary 3529
    50 Orszagos Koranyi Pulmonologiai Intezet /ID# 132738 Budapest XII Budapest Hungary 1122
    51 Debreceni Egyetem Klinikai Kozpont /ID# 132742 Debrecen Hungary 4032
    52 Koch Robert Hospital /ID# 133440 Edelény Hungary 3780
    53 Veszprem Megyei Tudogyogyintez /ID# 132739 Farkasgyepu Hungary 8582
    54 Petz Aladar Megyei Oktato Korh /ID# 132741 Gyor Hungary 9023
    55 Matrahaza Gyogyintezet /ID# 132743 Kékesteto Hungary 3233
    56 Assaf Harofeh Medical Center /ID# 132830 Be'er Ya'akov Israel 70300
    57 Shaare Zedek Medical Center /ID# 132834 Jerusalem Israel 91031
    58 Meir Medical Center /ID# 132832 Kfar Saba Israel 4428164
    59 Sheba Medical Center /ID# 132833 Ramat Gan Israel 5239424
    60 Aichi Cancer Center Hospital /ID# 134129 Nagoya-shi Aichi Japan 464-8681
    61 Kurume University Hospital /ID# 134117 Kurume-shi Fukuoka Japan 830-0011
    62 Hokkaido University Hospital /ID# 134123 Sapporo-shi Hokkaido Japan 060-8648
    63 Kanagawa Cardiovascular and Respiratory Center /ID# 134127 Yokohama-shi Kanagawa Japan 236-0051
    64 Sendai Kousei Hospital /ID# 135491 Sendai-shi Miyagi Japan 980-0873
    65 Kindai University Hospital /ID# 134112 Osaka-sayama-shi Osaka Japan 589-8511
    66 Osaka City General Hospital /ID# 134115 Osaka-shi Osaka Japan 534-0021
    67 National Cancer Center Hospital /ID# 135129 Chuo-ku Tokyo Japan 104-0045
    68 The Cancer Institute Hospital Of JFCR /ID# 135492 Koto-ku Tokyo Japan 135-8550
    69 Yamaguchi - Ube Medical Center /ID# 135284 Ube-shi Yamaguchi Japan 755-0241
    70 Hiroshima Citizens Hospital /ID# 135130 Hiroshima Japan 730-8518
    71 Kishiwada City Hospital /ID# 136548 Kishiwada Japan 596-8501
    72 Dong-A University Hospital /ID# 131609 Busan Busan Gwang Yeogsi Korea, Republic of 49201
    73 Seoul National Univ Bundang ho /ID# 131610 Seongnam Gyeonggido Korea, Republic of 13620
    74 Inha University Hospital /ID# 147924 Jung-gu Incheon Gwang Yeogsi Korea, Republic of 22332
    75 Chonnam National University Hospital /ID# 131612 Gwangju Jeonranamdo Korea, Republic of 61469
    76 Samsung Medical Center /ID# 132471 Seoul Seoul Teugbyeolsi Korea, Republic of 06351
    77 Chungbuk National Univ Hosp /ID# 131611 Cheongju Korea, Republic of 28644
    78 Vrije Universiteit Medisch Centrum /ID# 131967 Amsterdam Netherlands 1081 HV
    79 Catharina Ziekenhuis /ID# 131966 Eindhoven Netherlands 5623 EJ
    80 Ziekenhuis St. Jansdal /ID# 131965 Harderwijk Netherlands 3844 DG
    81 St. Antonius Ziekenhuis /ID# 133635 Nieuwegein Netherlands 3435 CM
    82 Jeroen Bosch Ziekenhuis /ID# 131968 S Hertogenbosch Netherlands 5223 GZ
    83 Canterbury District Health Boa /ID# 132469 Christchurch New Zealand 8011
    84 Wellington Hospital (Capital and Coast District Health Board) /ID# 132470 Wellington New Zealand 6021
    85 Federal State Budgetary Scientific Institution N.N. Blokhin Russian Cancer Resea /ID# 137085 Moscow Moskva Russian Federation 115478
    86 Sverdlovsk Regional Oncology Center Dispensary /ID# 132375 Ekaterinburg Sverdlovskaya Oblast Russian Federation 620043
    87 archangel Clinical Oncology /ID# 132376 Arkhangelsk Russian Federation 163045
    88 Moscow Regional Onc Dispensary /ID# 132381 Balashikha Russian Federation 143900
    89 Belgorod Oncology Dispensary /ID# 142638 Belgorod Russian Federation 308010
    90 Moscow Res Onc Inst Hertsen /ID# 132370 Moscow Russian Federation 125284
    91 State Regional Budgetary Healthcare Institution " Murmansk Regional Oncology Dis /ID# 137087 Murmansk Russian Federation 183047
    92 Orenburg Regional Clinical Onc /ID# 132371 Orenburg Russian Federation 460021
    93 Strategic medical systems LLC /ID# 206383 Sankt-Peterburg Russian Federation 192148
    94 Ogarev Mordovia State Univ /ID# 132377 Saransk Russian Federation 430005
    95 LLC BioEq Ltd. /ID# 132372 St. Petersburg Russian Federation 197342
    96 N.N. Petrov Research Inst Onc /ID# 137084 St. Petersburg Russian Federation 197758
    97 GVI Oncology /ID# 133268 Port Elizabeth Eastern Cape South Africa 6006
    98 Dr Albert, Bouwer and Jordaan Incorporated /ID# 131775 Pretoria Gauteng South Africa 0044
    99 Mary Potter Oncology Centre /ID# 131776 Pretoria Gauteng South Africa 0181
    100 The Oncology Centre /ID# 131773 Durban Kwazulu-Natal South Africa 4091
    101 Netcare Oncology Intervent Ctr /ID# 131777 Cape Town Western Cape South Africa 7460
    102 Cape Town Oncology Trials /ID# 132734 Cape Town Western Cape South Africa 7570
    103 GVI Rondebosch Oncology Centre /ID# 132732 Cape Town Western Cape South Africa 7700
    104 Sandton Oncology Medical Group /ID# 131774 Johannesburg South Africa 2196
    105 Hospital Duran i Reynals /ID# 132879 L'Hospitalet de Llobregat Barcelona Spain 08907
    106 Hospital Universitario Fundacion Alcorcon /ID# 132909 Alcorcon Spain 28922
    107 Hospital General Universitario Alicante /ID# 132881 Alicante Spain 03010
    108 Hospital Universitario Dexeus - Grupo Quironsalud /ID# 132876 Barcelona Spain 08028
    109 Hospital Universitario Vall d'Hebron /ID# 132871 Barcelona Spain 08035
    110 MD Anderson Madrid /ID# 132905 Madrid Spain 28033
    111 Hospital Universitario La Paz /ID# 132870 Madrid Spain 28046
    112 Hospital Universitario HM Sanchinarro /ID# 132869 Madrid Spain 28050
    113 Hospital Clinico Universitario de Valencia /ID# 132873 Valencia Spain 46010
    114 China Medical University Hosp /ID# 131870 Taichung City Taichung Taiwan 40447
    115 Dalin Tzu Chi General Hospital /ID# 131872 Dalin Township Taiwan 622
    116 Taipei Medical University Hospital /ID# 133817 Taipei City Taiwan 11031
    117 Taipei Veterans General Hosp /ID# 131871 Taipei City Taiwan 11217
    118 Hacettepe University Medical Faculty /ID# 131913 Ankara Turkey 06100
    119 Ankara Univ Medical Faculty /ID# 131914 Ankara Turkey 06590
    120 Uludag University Medical Faculty /ID# 131915 Bursa Turkey 16059
    121 Dicle Universitesi Tip /ID# 136570 Diyarbakir Turkey 21200
    122 Gaziantep Universitesi Med /ID# 131917 Gaziantep Turkey 27310
    123 Dr. Suat Seren Gogus Has /ID# 136568 Izmir Turkey 35110
    124 Inonu University /ID# 136569 Malatya Turkey 44280
    125 Leicester Royal Infirmary /ID# 133930 Leicester England United Kingdom LE1 5WW
    126 Cheltenham General Hospital /ID# 131951 Cheltenham Gloucestershire United Kingdom GL53 7AN
    127 Norfolk and Norwich Univ Hosp /ID# 131953 Norwich Norfolk United Kingdom NR4 7UY
    128 Royal United Hospitals Bath /ID# 132851 Bath United Kingdom BA1 3NG
    129 Belfast City Hospital /ID# 132858 Belfast United Kingdom BT9 7AB
    130 Heart of England NHS Foundation Trust /ID# 132855 Birmingham United Kingdom B9 5SS
    131 Royal Blackburn Hospital /ID# 132853 Blackburn United Kingdom BB2 3HH
    132 Colchester General Hospital /ID# 133929 Colchester United Kingdom CO4 5JL
    133 Castle Hill Hospital /ID# 135489 Cottingham United Kingdom HU16 5JQ
    134 Scunthorpe General Hospital /ID# 133931 Doncaster United Kingdom DN15 7BH
    135 James Paget University Hosp /ID# 131954 Great Yarmouth United Kingdom NR31 6LA
    136 Royal Gwent Hospital /ID# 133935 Gwent United Kingdom NP20 2UB
    137 Huddersfield Royal Infirmary /ID# 132854 Huddersfield United Kingdom HD3 3EA
    138 Charing Cross Hospital /ID# 131959 London United Kingdom W6 8RF
    139 The Newcastle Upon Tyne Hospitals NHS Foundation Trust Freeman Hospital /ID# 131661 Newcastle Upon Tyne United Kingdom NE7 7DN
    140 York Hospital /ID# 132859 York United Kingdom YO31 8HE

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: AbbVie Inc., AbbVie

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02264990
    Other Study ID Numbers:
    • M14-359
    • 2014-002565-30
    First Posted:
    Oct 15, 2014
    Last Update Posted:
    Feb 26, 2021
    Last Verified:
    Feb 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by AbbVie
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at 131 sites in 20 countries (Argentina, Australia, Canada, Czech Republic, Denmark, Finland, Germany, Hungary, Israel, Japan, South Korea, Netherlands, New Zealand, Russian Federation, South Africa, Spain, Taiwan, Turkey, United Kingdom, and United States).
    Pre-assignment Detail Participants were randomized in a 1:1 ratio to veliparib in combination with carboplatin and paclitaxel (C/P) or investigator's choice of platinum doublet chemotherapy. Randomization was stratified by smoking status (current versus former), by the investigators' preferred platinum doublet therapy (carboplatin/paclitaxel versus cisplatin/pemetrexed versus carboplatin/pemetrexed), by gender (male versus female) and by Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1).
    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Arm/Group Description Participants received investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin at an area under the curve (AUC) of 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Period Title: Overall Study
    STARTED 297 298
    Received Treatment 288 293
    Received Maintenance Therapy 148 123
    COMPLETED 37 39
    NOT COMPLETED 260 259

    Baseline Characteristics

    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel Total
    Arm/Group Description Participants received investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib BID on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Total of all reporting groups
    Overall Participants 297 298 595
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63.1
    (8.99)
    62.7
    (9.02)
    62.9
    (9.0)
    Age, Customized (Count of Participants)
    < 65 years
    153
    51.5%
    163
    54.7%
    316
    53.1%
    ≥ 65 years
    144
    48.5%
    135
    45.3%
    279
    46.9%
    Sex: Female, Male (Count of Participants)
    Female
    90
    30.3%
    92
    30.9%
    182
    30.6%
    Male
    207
    69.7%
    206
    69.1%
    413
    69.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    22
    7.4%
    26
    8.7%
    48
    8.1%
    Not Hispanic or Latino
    275
    92.6%
    272
    91.3%
    547
    91.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    White
    233
    78.5%
    229
    76.8%
    462
    77.6%
    Black
    11
    3.7%
    11
    3.7%
    22
    3.7%
    Asian
    53
    17.8%
    57
    19.1%
    110
    18.5%
    Other
    0
    0%
    1
    0.3%
    1
    0.2%
    Region (Count of Participants)
    US and Western Europe and Australia and Canada
    177
    59.6%
    157
    52.7%
    334
    56.1%
    Eastern Europe/Russia
    68
    22.9%
    88
    29.5%
    156
    26.2%
    Japan
    37
    12.5%
    35
    11.7%
    72
    12.1%
    Other Asian
    15
    5.1%
    18
    6%
    33
    5.5%
    Smoking Status (Count of Participants)
    Current smoker
    153
    51.5%
    152
    51%
    305
    51.3%
    Past smoker
    144
    48.5%
    146
    49%
    290
    48.7%
    Investigators' Preferred Platinum Doublet Therapy (Count of Participants)
    Carboplatin/paclitaxel
    71
    23.9%
    70
    23.5%
    141
    23.7%
    Cisplatin/pemetrexed
    95
    32%
    100
    33.6%
    195
    32.8%
    Carboplatin/pemetrexed
    131
    44.1%
    128
    43%
    259
    43.5%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
    Grade 0 (fully active)
    113
    38%
    116
    38.9%
    229
    38.5%
    Grade 1 (restricted but ambulatory)
    184
    62%
    182
    61.1%
    366
    61.5%
    Lung Subtype Panel (LSP) Assay Results (Count of Participants)
    LSP positive
    40
    13.5%
    40
    13.4%
    80
    13.4%
    LSP negative
    53
    17.8%
    74
    24.8%
    127
    21.3%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup
    Description Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.
    Time Frame From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT population who were LSP positive (LSP+)
    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Arm/Group Description Participants received investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib BID on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Measure Participants 40 40
    Median (95% Confidence Interval) [months]
    9.2
    11.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Investigator's Choice Chemotherapy, Veliparib + Carboplatin + Paclitaxel
    Comments
    Type of Statistical Test Superiority
    Comments A fixed sequence testing procedure was used for analyses of the primary and secondary efficacy endpoints to control for the familywise error rate. If veliparib plus C/P treatment was not statistically significantly better compared to the investigators' choice of standard therapy for the primary efficacy endpoint of OS in LSP+ participants, then statistical significance would not be declared for any of the secondary efficacy endpoints.
    Statistical Test of Hypothesis p-Value 0.113
    Comments Statistical significance was determined by a two-sided P value ≤ 0.05.
    Method Log Rank
    Comments Log rank test stratified by ECOG performance status, investigators' preferred platinum therapy, and gender.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.644
    Confidence Interval (2-Sided) 95%
    0.396 to 1.048
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio obtained using the covariate adjusted Cox Proportional Hazard Model with covariates being ECOG performance status, investigators' preferred platinum therapy, and gender.
    2. Secondary Outcome
    Title Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup
    Description Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death (all causes of mortality), whichever occurred first. PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cutoff date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.
    Time Frame From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT population who were LSP positive
    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Arm/Group Description Participants received investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib BID on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Measure Participants 40 40
    Median (95% Confidence Interval) [months]
    5.2
    6.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Investigator's Choice Chemotherapy, Veliparib + Carboplatin + Paclitaxel
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.260
    Comments
    Method Log Rank
    Comments Log-rank test stratified by investigator's preferred platinum therapy, gender, and ECOG performance status.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.647
    Confidence Interval (2-Sided) 95%
    0.388 to 1.080
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio was obtained using the covariate adjusted Cox Proportional Hazard Model with covariates of ECOG performance status, investigators' preferred platinum therapy, and gender.
    3. Secondary Outcome
    Title Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup
    Description Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed. CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.
    Time Frame Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT population who were LSP positive
    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Arm/Group Description Participants received investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib BID on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Measure Participants 40 40
    Number (95% Confidence Interval) [percentage of participants]
    30.0
    10.1%
    22.5
    7.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Investigator's Choice Chemotherapy, Veliparib + Carboplatin + Paclitaxel
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.455
    Comments
    Method Regression, Logistic
    Comments Logistic regression adjusted for the covariates of ECOG performance status, investigators' preferred platinum therapy, and gender.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.66
    Confidence Interval (2-Sided) 95%
    0.23 to 1.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio is from covariate adjusted logistic regression with the covariates being ECOG performance status, investigators' preferred platinum therapy, and gender.
    4. Secondary Outcome
    Title Overall Survival in All Participants
    Description Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. OS was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.
    Time Frame From randomization up to the data cut-off date of 15 July 2019; the median OS follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT population
    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Arm/Group Description Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib BID on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Measure Participants 297 298
    Median (95% Confidence Interval) [months]
    12.1
    12.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Investigator's Choice Chemotherapy, Veliparib + Carboplatin + Paclitaxel
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.846
    Comments
    Method Log Rank
    Comments Log rank test stratified by LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.986
    Confidence Interval (2-Sided) 95%
    0.827 to 1.176
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio was obtained using the covariate adjusted Cox Proportional Hazard Model with covariates of LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.
    5. Secondary Outcome
    Title Progression Free Survival (PFS) in All Participants
    Description Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per RECIST version 1.1 or death (all causes of mortality), whichever occurred first. PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.
    Time Frame From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT population
    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Arm/Group Description Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib BID on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Measure Participants 297 298
    Median (95% Confidence Interval) [months]
    6.7
    5.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Investigator's Choice Chemotherapy, Veliparib + Carboplatin + Paclitaxel
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.473
    Comments
    Method Log Rank
    Comments Log rank test stratified by LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.035
    Confidence Interval (2-Sided) 95%
    0.867 to 1.235
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio was obtained using the covariate adjusted Cox Proportional Hazard Model with covariates of LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.
    6. Secondary Outcome
    Title Objective Response Rate (ORR) in All Participants
    Description Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed. CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.
    Time Frame Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively.

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT population
    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Arm/Group Description Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib BID on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    Measure Participants 297 298
    Number (95% Confidence Interval) [percentage of participants]
    29.0
    9.8%
    26.2
    8.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Investigator's Choice Chemotherapy, Veliparib + Carboplatin + Paclitaxel
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.409
    Comments
    Method Regression, Logistic
    Comments Logistic regression adjusted for the covariates of LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.86
    Confidence Interval (2-Sided) 95%
    0.59 to 1.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio is from covariate adjusted logistic regression with the covariates being LSP status, ECOG performance status, investigators' preferred platinum therapy, and gender.

    Adverse Events

    Time Frame All-cause mortality: From randomization until the end of study; the median follow-up time was 45.4 and 44.6 months in each treatment group, respectively. Adverse events: From first dose of study drug until 30 days after last dose of study drug (veliparib or investigators' choice of standard chemotherapy); median duration of treatment ranged from 86 to 111 days for each treatment.
    Adverse Event Reporting Description All-cause mortality is reported for all randomized participants. Adverse events are reported for the as-treated subjects population, which included all participants who received at least 1 dose of study drug (veliparib/investigator's choice of standard chemotherapy).
    Arm/Group Title Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Arm/Group Description Participants received investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m² Cisplatin 75 mg/m² + pemetrexed 500 mg/m² Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an AUC of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
    All Cause Mortality
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 255/297 (85.9%) 250/298 (83.9%)
    Serious Adverse Events
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 98/288 (34%) 121/293 (41.3%)
    Blood and lymphatic system disorders
    ANAEMIA 15/288 (5.2%) 17 7/293 (2.4%) 8
    FEBRILE NEUTROPENIA 7/288 (2.4%) 10 13/293 (4.4%) 15
    LEUKOPENIA 0/288 (0%) 0 2/293 (0.7%) 2
    LYMPHADENITIS 0/288 (0%) 0 1/293 (0.3%) 1
    NEUTROPENIA 5/288 (1.7%) 5 6/293 (2%) 9
    PANCYTOPENIA 1/288 (0.3%) 1 0/293 (0%) 0
    THROMBOCYTOPENIA 6/288 (2.1%) 6 2/293 (0.7%) 2
    Cardiac disorders
    ARTERIOSPASM CORONARY 0/288 (0%) 0 1/293 (0.3%) 1
    ATRIAL FIBRILLATION 2/288 (0.7%) 2 4/293 (1.4%) 4
    ATRIAL FLUTTER 0/288 (0%) 0 1/293 (0.3%) 1
    CARDIAC ARREST 2/288 (0.7%) 2 0/293 (0%) 0
    CARDIAC FAILURE 1/288 (0.3%) 1 1/293 (0.3%) 1
    CARDIAC FAILURE ACUTE 1/288 (0.3%) 1 0/293 (0%) 0
    CARDIO-RESPIRATORY ARREST 1/288 (0.3%) 1 1/293 (0.3%) 1
    CARDIOPULMONARY FAILURE 1/288 (0.3%) 1 2/293 (0.7%) 2
    LEFT VENTRICULAR FAILURE 0/288 (0%) 0 1/293 (0.3%) 1
    PERICARDIAL EFFUSION 0/288 (0%) 0 7/293 (2.4%) 7
    PERICARDITIS 1/288 (0.3%) 2 0/293 (0%) 0
    SUPRAVENTRICULAR TACHYCARDIA 0/288 (0%) 0 1/293 (0.3%) 1
    Gastrointestinal disorders
    ABDOMINAL PAIN 2/288 (0.7%) 4 2/293 (0.7%) 2
    APHTHOUS ULCER 0/288 (0%) 0 1/293 (0.3%) 1
    ASCITES 1/288 (0.3%) 1 0/293 (0%) 0
    COLITIS ISCHAEMIC 0/288 (0%) 0 1/293 (0.3%) 1
    COLITIS ULCERATIVE 1/288 (0.3%) 1 0/293 (0%) 0
    CONSTIPATION 1/288 (0.3%) 1 2/293 (0.7%) 2
    DIARRHOEA 2/288 (0.7%) 2 2/293 (0.7%) 2
    GASTRITIS 0/288 (0%) 0 1/293 (0.3%) 1
    HAEMATEMESIS 1/288 (0.3%) 1 0/293 (0%) 0
    INTESTINAL OBSTRUCTION 1/288 (0.3%) 1 0/293 (0%) 0
    MESENTERIC VEIN THROMBOSIS 0/288 (0%) 0 1/293 (0.3%) 1
    NAUSEA 3/288 (1%) 3 3/293 (1%) 3
    OESOPHAGEAL STENOSIS 0/288 (0%) 0 1/293 (0.3%) 1
    OESOPHAGITIS 0/288 (0%) 0 1/293 (0.3%) 1
    RECTAL HAEMORRHAGE 1/288 (0.3%) 1 0/293 (0%) 0
    VOMITING 5/288 (1.7%) 5 6/293 (2%) 6
    General disorders
    ASTHENIA 2/288 (0.7%) 2 1/293 (0.3%) 2
    CATHETER SITE HAEMORRHAGE 0/288 (0%) 0 1/293 (0.3%) 1
    CHEST PAIN 0/288 (0%) 0 1/293 (0.3%) 1
    DISEASE PROGRESSION 0/288 (0%) 0 1/293 (0.3%) 1
    FATIGUE 2/288 (0.7%) 2 0/293 (0%) 0
    GENERAL PHYSICAL HEALTH DETERIORATION 1/288 (0.3%) 2 0/293 (0%) 0
    MALAISE 3/288 (1%) 6 0/293 (0%) 0
    MULTIPLE ORGAN DYSFUNCTION SYNDROME 2/288 (0.7%) 2 0/293 (0%) 0
    NON-CARDIAC CHEST PAIN 0/288 (0%) 0 2/293 (0.7%) 2
    PERIPHERAL SWELLING 0/288 (0%) 0 1/293 (0.3%) 1
    PYREXIA 1/288 (0.3%) 1 0/293 (0%) 0
    SUDDEN DEATH 1/288 (0.3%) 1 2/293 (0.7%) 2
    SYSTEMIC INFLAMMATORY RESPONSE SYNDROME 0/288 (0%) 0 1/293 (0.3%) 1
    Hepatobiliary disorders
    HEPATIC FUNCTION ABNORMAL 0/288 (0%) 0 1/293 (0.3%) 1
    Immune system disorders
    ANAPHYLACTIC SHOCK 0/288 (0%) 0 1/293 (0.3%) 1
    DRUG HYPERSENSITIVITY 1/288 (0.3%) 1 3/293 (1%) 4
    Infections and infestations
    ABDOMINAL ABSCESS 1/288 (0.3%) 1 0/293 (0%) 0
    APPENDICITIS PERFORATED 1/288 (0.3%) 1 0/293 (0%) 0
    BACTERAEMIA 0/288 (0%) 0 1/293 (0.3%) 1
    BRONCHITIS 1/288 (0.3%) 1 1/293 (0.3%) 1
    CELLULITIS 1/288 (0.3%) 1 1/293 (0.3%) 1
    CLOSTRIDIUM DIFFICILE COLITIS 0/288 (0%) 0 1/293 (0.3%) 1
    DEVICE RELATED INFECTION 1/288 (0.3%) 1 0/293 (0%) 0
    DIARRHOEA INFECTIOUS 0/288 (0%) 0 1/293 (0.3%) 1
    EMPYEMA 0/288 (0%) 0 1/293 (0.3%) 1
    GASTROENTERITIS 0/288 (0%) 0 1/293 (0.3%) 1
    HERPES ZOSTER 0/288 (0%) 0 1/293 (0.3%) 1
    INFECTION 2/288 (0.7%) 2 0/293 (0%) 0
    INFLUENZA 0/288 (0%) 0 2/293 (0.7%) 2
    LOWER RESPIRATORY TRACT INFECTION 1/288 (0.3%) 1 4/293 (1.4%) 4
    LUNG INFECTION 0/288 (0%) 0 2/293 (0.7%) 2
    LYMPHANGITIS 0/288 (0%) 0 1/293 (0.3%) 1
    NEUTROPENIC SEPSIS 0/288 (0%) 0 1/293 (0.3%) 1
    PERITONSILLAR ABSCESS 1/288 (0.3%) 2 0/293 (0%) 0
    PNEUMONIA 8/288 (2.8%) 9 19/293 (6.5%) 26
    PNEUMONIA BACTERIAL 0/288 (0%) 0 1/293 (0.3%) 1
    PNEUMONIA PSEUDOMONAL 0/288 (0%) 0 1/293 (0.3%) 1
    PSEUDOMONAL SEPSIS 0/288 (0%) 0 1/293 (0.3%) 1
    PULMONARY SEPSIS 0/288 (0%) 0 1/293 (0.3%) 1
    PYELONEPHRITIS 1/288 (0.3%) 1 0/293 (0%) 0
    RESPIRATORY TRACT INFECTION 1/288 (0.3%) 1 1/293 (0.3%) 1
    SEPSIS 4/288 (1.4%) 5 1/293 (0.3%) 1
    SEPTIC SHOCK 1/288 (0.3%) 1 2/293 (0.7%) 2
    UPPER RESPIRATORY TRACT INFECTION 0/288 (0%) 0 1/293 (0.3%) 2
    URINARY TRACT INFECTION 2/288 (0.7%) 2 2/293 (0.7%) 2
    VASCULAR DEVICE INFECTION 0/288 (0%) 0 1/293 (0.3%) 1
    VIRAL UPPER RESPIRATORY TRACT INFECTION 0/288 (0%) 0 1/293 (0.3%) 1
    Injury, poisoning and procedural complications
    FALL 1/288 (0.3%) 1 1/293 (0.3%) 1
    FEMORAL NECK FRACTURE 1/288 (0.3%) 1 0/293 (0%) 0
    HEART INJURY 0/288 (0%) 0 1/293 (0.3%) 2
    HIP FRACTURE 0/288 (0%) 0 1/293 (0.3%) 1
    LUMBAR VERTEBRAL FRACTURE 0/288 (0%) 0 1/293 (0.3%) 1
    RADIATION OESOPHAGITIS 1/288 (0.3%) 1 0/293 (0%) 0
    SPINAL COMPRESSION FRACTURE 0/288 (0%) 0 1/293 (0.3%) 1
    Investigations
    C-REACTIVE PROTEIN INCREASED 1/288 (0.3%) 1 0/293 (0%) 0
    Metabolism and nutrition disorders
    DECREASED APPETITE 2/288 (0.7%) 2 2/293 (0.7%) 2
    DEHYDRATION 6/288 (2.1%) 6 0/293 (0%) 0
    HYPOCALCAEMIA 1/288 (0.3%) 1 0/293 (0%) 0
    HYPOGLYCAEMIA 1/288 (0.3%) 1 1/293 (0.3%) 1
    HYPONATRAEMIA 2/288 (0.7%) 2 1/293 (0.3%) 1
    TYPE 2 DIABETES MELLITUS 0/288 (0%) 0 1/293 (0.3%) 1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/288 (0%) 0 1/293 (0.3%) 1
    BACK PAIN 2/288 (0.7%) 2 3/293 (1%) 3
    BONE PAIN 1/288 (0.3%) 1 0/293 (0%) 0
    MUSCULOSKELETAL CHEST PAIN 1/288 (0.3%) 2 1/293 (0.3%) 1
    MUSCULOSKELETAL PAIN 1/288 (0.3%) 1 0/293 (0%) 0
    PAIN IN EXTREMITY 1/288 (0.3%) 1 1/293 (0.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CANCER PAIN 0/288 (0%) 0 1/293 (0.3%) 1
    GASTRIC CANCER 0/288 (0%) 0 1/293 (0.3%) 1
    MALIGNANT NEOPLASM PROGRESSION 10/288 (3.5%) 12 14/293 (4.8%) 19
    MALIGNANT PLEURAL EFFUSION 1/288 (0.3%) 1 0/293 (0%) 0
    METASTASES TO BONE 0/288 (0%) 0 1/293 (0.3%) 1
    METASTASES TO CENTRAL NERVOUS SYSTEM 1/288 (0.3%) 1 4/293 (1.4%) 4
    METASTASES TO MENINGES 1/288 (0.3%) 1 0/293 (0%) 0
    PERICARDIAL EFFUSION MALIGNANT 0/288 (0%) 0 1/293 (0.3%) 1
    Nervous system disorders
    CEREBRAL INFARCTION 0/288 (0%) 0 2/293 (0.7%) 2
    CEREBRAL ISCHAEMIA 0/288 (0%) 0 1/293 (0.3%) 2
    CEREBROVASCULAR ACCIDENT 1/288 (0.3%) 1 0/293 (0%) 0
    COGNITIVE DISORDER 0/288 (0%) 0 1/293 (0.3%) 1
    PERIPHERAL SENSORY NEUROPATHY 0/288 (0%) 0 1/293 (0.3%) 1
    SPINAL CORD COMPRESSION 1/288 (0.3%) 1 1/293 (0.3%) 1
    Psychiatric disorders
    CONFUSIONAL STATE 1/288 (0.3%) 1 1/293 (0.3%) 1
    DELIRIUM 0/288 (0%) 0 2/293 (0.7%) 2
    DEPRESSION 0/288 (0%) 0 1/293 (0.3%) 1
    DISORIENTATION 0/288 (0%) 0 1/293 (0.3%) 1
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 1/288 (0.3%) 1 1/293 (0.3%) 1
    AZOTAEMIA 1/288 (0.3%) 1 0/293 (0%) 0
    HAEMATURIA 0/288 (0%) 0 1/293 (0.3%) 1
    RENAL FAILURE 1/288 (0.3%) 1 0/293 (0%) 0
    RENAL IMPAIRMENT 1/288 (0.3%) 1 0/293 (0%) 0
    URINARY RETENTION 1/288 (0.3%) 1 0/293 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE 1/288 (0.3%) 2 2/293 (0.7%) 2
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE 1/288 (0.3%) 1 2/293 (0.7%) 2
    DYSPNOEA 7/288 (2.4%) 9 8/293 (2.7%) 8
    DYSPNOEA EXERTIONAL 1/288 (0.3%) 1 0/293 (0%) 0
    HAEMOPTYSIS 3/288 (1%) 3 1/293 (0.3%) 1
    HYPOXIA 1/288 (0.3%) 1 0/293 (0%) 0
    ORGANISING PNEUMONIA 0/288 (0%) 0 1/293 (0.3%) 1
    PLEURAL EFFUSION 6/288 (2.1%) 9 5/293 (1.7%) 7
    PLEURITIC PAIN 1/288 (0.3%) 1 0/293 (0%) 0
    PNEUMONIA ASPIRATION 0/288 (0%) 0 1/293 (0.3%) 1
    PNEUMOTHORAX 0/288 (0%) 0 1/293 (0.3%) 1
    PRODUCTIVE COUGH 1/288 (0.3%) 1 0/293 (0%) 0
    PULMONARY EMBOLISM 6/288 (2.1%) 6 5/293 (1.7%) 5
    PULMONARY HAEMORRHAGE 2/288 (0.7%) 2 0/293 (0%) 0
    RESPIRATORY DISTRESS 0/288 (0%) 0 1/293 (0.3%) 1
    RESPIRATORY FAILURE 2/288 (0.7%) 3 2/293 (0.7%) 2
    RHINORRHOEA 0/288 (0%) 0 1/293 (0.3%) 1
    Skin and subcutaneous tissue disorders
    SUBCUTANEOUS EMPHYSEMA 0/288 (0%) 0 1/293 (0.3%) 1
    Vascular disorders
    ANEURYSM 0/288 (0%) 0 1/293 (0.3%) 1
    AXILLARY VEIN THROMBOSIS 0/288 (0%) 0 1/293 (0.3%) 1
    DEEP VEIN THROMBOSIS 2/288 (0.7%) 2 0/293 (0%) 0
    HYPOTENSION 1/288 (0.3%) 1 2/293 (0.7%) 2
    HYPOVOLAEMIC SHOCK 1/288 (0.3%) 1 0/293 (0%) 0
    ORTHOSTATIC HYPOTENSION 2/288 (0.7%) 2 0/293 (0%) 0
    VENOUS THROMBOSIS 1/288 (0.3%) 1 0/293 (0%) 0
    Other (Not Including Serious) Adverse Events
    Investigator's Choice Chemotherapy Veliparib + Carboplatin + Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 269/288 (93.4%) 275/293 (93.9%)
    Blood and lymphatic system disorders
    ANAEMIA 107/288 (37.2%) 197 112/293 (38.2%) 212
    LEUKOPENIA 40/288 (13.9%) 77 43/293 (14.7%) 77
    NEUTROPENIA 89/288 (30.9%) 175 104/293 (35.5%) 210
    THROMBOCYTOPENIA 54/288 (18.8%) 102 76/293 (25.9%) 155
    Gastrointestinal disorders
    CONSTIPATION 92/288 (31.9%) 113 69/293 (23.5%) 81
    DIARRHOEA 47/288 (16.3%) 60 51/293 (17.4%) 70
    NAUSEA 131/288 (45.5%) 202 86/293 (29.4%) 121
    STOMATITIS 30/288 (10.4%) 32 19/293 (6.5%) 24
    VOMITING 73/288 (25.3%) 99 39/293 (13.3%) 48
    General disorders
    ASTHENIA 30/288 (10.4%) 50 29/293 (9.9%) 58
    FATIGUE 89/288 (30.9%) 117 80/293 (27.3%) 108
    OEDEMA PERIPHERAL 24/288 (8.3%) 36 13/293 (4.4%) 16
    PYREXIA 16/288 (5.6%) 21 15/293 (5.1%) 17
    Investigations
    WEIGHT DECREASED 24/288 (8.3%) 25 14/293 (4.8%) 17
    Metabolism and nutrition disorders
    DECREASED APPETITE 79/288 (27.4%) 109 63/293 (21.5%) 79
    HYPERGLYCAEMIA 11/288 (3.8%) 15 24/293 (8.2%) 24
    HYPOMAGNESAEMIA 16/288 (5.6%) 19 21/293 (7.2%) 22
    HYPONATRAEMIA 12/288 (4.2%) 14 16/293 (5.5%) 18
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 26/288 (9%) 35 39/293 (13.3%) 45
    BACK PAIN 22/288 (7.6%) 24 17/293 (5.8%) 21
    BONE PAIN 9/288 (3.1%) 13 15/293 (5.1%) 21
    MYALGIA 17/288 (5.9%) 22 38/293 (13%) 50
    PAIN IN EXTREMITY 15/288 (5.2%) 19 15/293 (5.1%) 17
    Nervous system disorders
    DIZZINESS 22/288 (7.6%) 25 17/293 (5.8%) 17
    DYSGEUSIA 29/288 (10.1%) 33 19/293 (6.5%) 20
    PERIPHERAL SENSORY NEUROPATHY 42/288 (14.6%) 51 131/293 (44.7%) 195
    Psychiatric disorders
    INSOMNIA 30/288 (10.4%) 30 37/293 (12.6%) 39
    Respiratory, thoracic and mediastinal disorders
    COUGH 29/288 (10.1%) 31 27/293 (9.2%) 32
    DYSPNOEA 25/288 (8.7%) 30 42/293 (14.3%) 46
    HICCUPS 21/288 (7.3%) 29 17/293 (5.8%) 27
    OROPHARYNGEAL PAIN 15/288 (5.2%) 16 6/293 (2%) 8
    Skin and subcutaneous tissue disorders
    ALOPECIA 34/288 (11.8%) 40 137/293 (46.8%) 160
    RASH 25/288 (8.7%) 29 13/293 (4.4%) 16

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.

    Results Point of Contact

    Name/Title Global Medical Services
    Organization AbbVie
    Phone 800-633-9110
    Email abbvieclinicaltrials@abbvie.com
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02264990
    Other Study ID Numbers:
    • M14-359
    • 2014-002565-30
    First Posted:
    Oct 15, 2014
    Last Update Posted:
    Feb 26, 2021
    Last Verified:
    Feb 1, 2021