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GAMMA-1: Andecaliximab With mFOLFOX6 as First Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02545504
Collaborator
(none)
432
Enrollment
134
Locations
2
Arms
43
Actual Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to compare the efficacy of andecaliximab (GS-5745) versus placebo in combination with modified fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (OXA) (mFOLFOX6) as measured by overall survival.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
432 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-5745 Combined With mFOLFOX6 as First Line Treatment in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Actual Study Start Date :
Oct 13, 2015
Actual Primary Completion Date :
May 15, 2019
Actual Study Completion Date :
May 15, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Andecaliximab

Andecaliximab plus mFOLFOX6 (LV+5-FU+OXA) during Cycles 1-6, followed by andecaliximab plus LV+5-FU during subsequent cycles

Drug: Andecaliximab
800 mg administered intravenously on Days 1 and 15 of each 28-day treatment cycle
Other Names:
  • GS-5745

    • Drug: Leucovorin
    Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle
    Other Names:
  • LV

    • Drug: 5-fluorouracil
    Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle
    Other Names:
  • 5-FU

    • Drug: Oxaliplatin
    Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle
    Other Names:
  • OXA

    		•
    Placebo Comparator: Placebo

    Placebo plus mFOLFOX6 (LV+5-FU+OXA) during Cycles 1-6, followed by placebo plus LV+5-FU during subsequent cycles

    Drug: Placebo
    Administered intravenously on Days 1 and 15 of each treatment cycle

    Drug: Leucovorin
    Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle
    Other Names:
  • LV

    • Drug: 5-fluorouracil
    Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle
    Other Names:
  • 5-FU

    • Drug: Oxaliplatin
    Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle
    Other Names:
  • OXA

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Andecaliximab + mFOLFOX6 median follow-up at the time of final analysis: 19.43 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 19.45 months]

      OS was defined as the time interval from the date of randomization to death from any cause.

    Secondary Outcome Measures

    1. Progression-free Survival (PFS) [Andecaliximab + mFOLFOX6 median follow-up at the time of the final analysis: 18.64 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 18.74 months]

      PFS was defined as the interval of time from the date of randomization to the earlier of the first documentation of definitive disease progression or death from any cause.

    2. Objective Response Rate (ORR) [Up to 135.4 weeks at the time of final analysis]

      ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    3. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [First dose date up to the last dose date (maximum:161.7 weeks) plus 30 to 55 days]

      An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. TEAEs are events in a given study period that meet any of the following criteria: Any AE with onset date of on or after andecalizimab/placebo start date and no later than 30 days after permanent discontinuation of all study treatment (andecaliximab/placebo and chemotherapy) or Any AEs with onset date of on or after the andecaliximab/placebo start date and no later than 55 days after permanent discontinuation of andecaliximab/placebo or AEs leading to discontinuation of andecaliximab/placebo.

    4. Percentage of Participants With Clinically Relevant Treatment-emergent Laboratory Abnormalities [First dose date up to the last dose date (maximum: 161.7 weeks) plus 30 to 55 days]

      Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 0=None, 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening. Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any post-baseline time point, up to 30 days after the last dose of all study treatment, or 55 days after the last dose of andecaliximab/placebo for participants who permanently discontinued all study treatments. If the relevant baseline laboratory value is missing, then any abnormality of at least Grade 1 was considered treatment-emergent.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Adults with histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction that is inoperable, locally advanced or metastatic and not amenable to curative therapy

    • Adequate hematologic, liver, coagulation and kidney function

    • Eastern Cooperative Oncology Group (ECOG) ≤ 1

    • Evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1

    Key Exclusion Criteria:

    • Previous chemotherapy for locally advanced or metastatic gastric cancer.

    • Human Epidermal Growth Factor Receptor 2 (HER2)-positive gastric cancer

    • HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection

    • Pregnant or breast feeding women

    • Individuals with known or suspected central nervous system metastases or individuals requiring chronic daily treatment with oral corticosteroids

    • Grade ≥ 2 peripheral neuropathy

    Note: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Scripps Green Hospital La Jolla California United States 92037
    2 University of Southern California Los Angeles California United States 90007
    3 UCLA Jonsson Comprehensive Cancer Center Los Angeles California United States 90024
    4 Innovative Clinical Research Institute Whittier California United States 90603
    5 Cancer Center of Central Connecticut Plainville Connecticut United States 06062
    6 Omega Research Consultants LLC DeBary Florida United States 32713
    7 Edward Hospital & Health Services Naperville Illinois United States 60540
    8 Parkview Hospital Fort Wayne Indiana United States 46805
    9 Indiana University Goshen Center for Cancer Care Goshen Indiana United States 46526
    10 Ochsner Clinic Foundation New Orleans Louisiana United States 70816
    11 New England Cancer Specialists Scarborough Maine United States 04074
    12 Karamanos Cancer Institute Detroit Michigan United States 48175
    13 HCA Healthcare Kansas City Missouri United States 64030
    14 Carol G. Simon Cancer Center Morristown New Jersey United States 07901
    15 Regional Cancer Care Associates LLC - Sparta Sparta New Jersey United States 07871
    16 Weill Cornell Medical College - New York Presbyterian Hospital New York New York United States 10065
    17 University of Rochester Rochester New York United States 14627
    18 Duke Cancer Institute Durham North Carolina United States 27710
    19 Oncology Hematology Care, Inc. Cincinnati Ohio United States 45242
    20 The Ohio State Medical Center Columbus Ohio United States 43210
    21 Northwest Cancer Specialists Portland Oregon United States 97213
    22 Charleston Hematology Oncology Associates Charleston South Carolina United States 29403
    23 Prairie Lakes Health Care System INC Watertown South Dakota United States
    24 Tennessee Oncology Nashville Tennessee United States
    25 Center for Cancer Blood Disorders Fort Worth Texas United States
    26 The University of Texas MD Anderson Cancer Center Houston Texas United States
    27 Texas Oncology-Seton Williamson Round Rock Texas United States
    28 Scott and White Memorial Hospital Temple Texas United States
    29 Utah Cancer Specialists Salt Lake City Utah United States
    30 Virginia Commonwealth University Richmond Virginia United States
    31 Virginia Mason Seattle Main Clinic Seattle Washington United States
    32 The Canberra Hospital Garran Australian Capital Territory Australia
    33 Chris O'Brien Lifehouse Camperdown New South Wales Australia
    34 The Crown Princess Mary Cancer Centre Westmead New South Wales Australia
    35 Princess Alexandra Hospital Brisbane Queensland Australia
    36 Ashford Cancer Centre Kurralta Park South Australia Australia
    37 Royal Hobart Hospital Hobart Tasmania Australia
    38 Epworth Healthcare Richmond Victoria Australia
    39 Western Health Sunshine Hospital St Albans Victoria Australia
    40 The Tweed Hospital Tweed Heads Australia 2485
    41 Sydney Adventist Hospital Wahroonga Australia
    42 Centre Hospitalizer De L'Ardenne Libramont Chevigny Belgium
    43 University Hospital Gent Department of Gastroenterology Gent Belgium
    44 Instituto Nacional Del Cancer Santiago Chile
    45 Instituto Clinico Oncologico del Sur Temuco Chile
    46 Hospital Clinico Vina Del Mar Vina del Mar Chile
    47 Oncomedica S.A Monteria Cordoba Colombia
    48 Dundacion Oftalmologica de Santander Clinica Ardila Lulle La Foscal Floridablanca Colombia
    49 Hospital Pablo Tobon Uribe Medellin Colombia
    50 Centro Medico Imbanaco de Cali S.A Valle Colombia
    51 Fakultni Nemocnice Brno Brno Czechia
    52 Fakultni nemocnice Hradec Kralove Hradec Kralove Czechia
    53 University Hospital - Czech Olomouc Czechia
    54 Thomayer Hospital Prague 4 Czechia
    55 Oblastni Nemocnice Pribram Pribram Czechia
    56 CHU Jean Minjoz Besancon France
    57 CHRU de Brest, Hopital Morvan, Institut de Cancerologie et d'Hematologie Brest Cedex France
    58 Hôpitaux Civils de Colmar Colmar France
    59 Institut Paoli Calmettes Marseille Cedex 9 France
    60 CHU de Nice-l Archet Nice Cedex 3 France
    61 CH Annecy-Gennevois Pringy Cedex France
    62 Kliniken Nordoberpfalz AG Weiden Bavaria Germany
    63 Klinikum rechts der Isar Technical University of Ismaninger Munich Bayern Germany
    64 DRK Klinken Berlin Abteilungsleiter Chiurgische Okologie Berlin Germany
    65 Universitätsklinikum Carl Gustav Carus Dresden Germany
    66 Kliniken Essen Mitte Studiensekretariat Onkologie Evang. Huyssens-Stiftung Essen Germany
    67 Krankenhaus Nordwest gGmbH Institut für Klinisch Onkologische Med Klinik II Frankfurt Germany
    68 Cancer Center Heilbronn-Franken, SLK-Kliniken Heilbronn Germany
    69 Staedtisches Klinikum Muenchen Bogenhausen Muenchen Germany
    70 Zentrum fur Innere Medizin Stauferklinikum Schwab Mutlangen Germany
    71 Universitatsklinikum Ulm Ulm Germany
    72 Egyesített Szent István és Szent László Kórház -Rendelőintézet Budapest Hungary
    73 Debreceni Egyetem Klinikai Központ Debrecen Hungary
    74 Human Klinikai Vizsgalatok Regisztracios Kozpont - HKVRK Gyor Hungary
    75 Pandy Kalman Hospital Gyula Hungary
    76 Borsod County Hospital Clinical Oncological and Radiotheraputic Center Miskolc Hungary
    77 Zala Megyei Korhaz Pozva Diabetes Kulsokorhaz Zalaegerszeg Hungary
    78 University Hospital Company of Pisana Pisa PI Italy
    79 Ente Ospedaliero Ospedali Galliera Genova Italy
    80 IRCCS A.O.U. San Martino Genova Italy
    81 Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy
    82 Ospedale San Raffaele Milano Italy
    83 S.C. Oncologia Medica Azienda Ospedaliera Valtellina e Valchiavenna Presidio Ospedaliero di Sondrio Sondrio Italy
    84 Azienda Ospedaliera Treviglio Caravaggio U.O. Oncologia Medica Treviglio Italy
    85 Centro de Investigacion Instituto de oncologia y Radiotherpia de la Clinica San Isidro Lima Peru
    86 Centro Medico monte Carmelo Arequipa Peru
    87 Clinica Anglo Americana Calle Alfredo Salazar San Isidro Peru
    88 Beskidzkie Oncology Center Bielsko-Biala Poland
    89 Wojewodzki Szpital Zespolony w Elblagu Oddzial Onkologiczny Elblag Poland
    90 Wielkopolskie Centrum Onkologii Poznan Poland
    91 Mrukmed Lekarz Beata Madej Mruk i Partner Spolka Partnerska Oddzial Nr 1 w Rzeszowie Rzeszow Poland
    92 Wojewodzki Szpital Zespolony im L Rydygiera w Toruniu Torun Poland
    93 Wojskowy Instytut Medyczny Warsaw Poland
    94 Klinka Gastroenterologii Okologicznej Centrum Okologii Instytut Warszawa Poland
    95 Medisprof srl Oncologie P TA Cluj-Napoca Judet Cluj Romania
    96 Fundeni Clinical Institute Bucuresti Romania
    97 GRAL Medical SRL Bucuresti Romania
    98 Centrul de Oncologie Sfantul Nectarie SRL, Oncologie Craiova Romania
    99 Sc Oncolab Srl Craiova Romania
    100 SC Centrul de Oncologie Euroclinic SRL, Oncologie Iaşi Romania
    101 Spitalul Judetean De Urgenta Sf Ion Cel Nou Suceava Sectia Oncologie Medicala Bdul Suceava Romania
    102 Hospital Universitario de A Coruna C A Coruna Spain
    103 Hospital Clinic de Barcelona Barcelona Spain
    104 Hospital Del Mar Servicio de Oncologia Barcelona Spain
    105 Hospital Parc Tauli Barcelona Spain
    106 Hospital Universitari Vall d'Hebron Barcelona Spain
    107 Institut Catala de la Salut Barcelona Spain
    108 Hospital General Universitario Gregorio Maranon Madrid Spain
    109 Hospital Ramon y Cajal Madrid Spain
    110 Hospital Universitario La Paz Madrid Spain
    111 Hospital Universitario Puerta de Hierro Madrid Spain
    112 Hospital Regional Universitario de Malaga Malaga Spain
    113 Hospital Universitario Morales Meseguer Murcia Spain
    114 Complejo Hospitalario de Navarra Pamplona Spain
    115 Hospital Virgen de Valme Sevilla Spain
    116 Cukurova Universitesi Adana Turkey
    117 Ankara University Medical Faculty Ibni Sina Hospital Ankara Turkey
    118 Hacettepe Universitesi Tip Facultesi Cocuk Saligi ve Hastaklikleri Anabilim Dali Ankara Turkey
    119 Hacettepe University Ankara Turkey
    120 University of Uludag Bursa Turkey
    121 Trakya University Edirne Turkey
    122 Bezmialem University Hospital Istanbul Turkey
    123 Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi Istanbul Turkey
    124 Istanbul Universitesi Onkoloji Enstitusu Medikal Onkoloji Bilim Dali Istanbul Turkey
    125 Marmara University Kadikoy Turkey
    126 Izmir Universitesi Hastanesi Yeni Girne Vulvari Karsiyaka Turkey
    127 Kocaeli Universty Kocaeli Turkey
    128 Inonu Universitesi Turgut Ozal Tip Merkezi Elazi Malatya Turkey
    129 Van Yuzuncu Yil Universitesi Tip Kaultesi Ic Hastaliklari Anabilim Dali Tibbi Okoloji Bilim Dali Van Turkey
    130 New Queen Elizabeth Hospital Birmingham United Kingdom
    131 Peterborough City Hospital Peterborough and Stamford Hospitals NHS Foundation Trust Cambridge United Kingdom
    132 Royal Marsden Hospital Mulberry House London United Kingdom
    133 University College London London United Kingdom
    134 Christie Hospital NHS Foundation Trust Manchester United Kingdom

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02545504
    Other Study ID Numbers:
    • GS-US-296-1080
    • 2015-001526-42
    First Posted:
    Sep 10, 2015
    Last Update Posted:
    May 26, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gilead Sciences
    Gastroesophageal junction (GEJ)
    Stomach cancer
    Additional relevant MeSH terms:
    Adenocarcinoma
    Leucovorin
    Fluorouracil
    Oxaliplatin

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in Australia, Europe, Chile, Colombia, Peru, Turkey, and the United States. The first participant was screened on 13 October 2015. The last study visit occurred on 15 May 2019.
    Pre-assignment Detail 635 participants were screened.
    Arm/Group Title Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Arm/Group Description Participants were randomized to receive andecaliximab 800 mg intravenous (IV) plus mFOLFOX6 [leucovorin (LV)+5-fluorouracil (5-FU) + oxaliplatin (OXA)] IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 161.7 weeks. Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 112.3 weeks.
    Period Title: Overall Study
    STARTED 218 214
    COMPLETED 0 0
    NOT COMPLETED 218 214

    Baseline Characteristics

    Arm/Group Title Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6 Total
    Arm/Group Description Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 161.7 weeks. Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 112.3 weeks. Total of all reporting groups
    Overall Participants 218 214 432
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60
    (11.9)
    61
    (11.4)
    60
    (11.7)
    Sex: Female, Male (Count of Participants)
    Female
    50
    22.9%
    61
    28.5%
    111
    25.7%
    Male
    168
    77.1%
    153
    71.5%
    321
    74.3%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    0.5%
    1
    0.2%
    Asian
    5
    2.3%
    5
    2.3%
    10
    2.3%
    Black or African American
    4
    1.8%
    4
    1.9%
    8
    1.9%
    White
    186
    85.3%
    184
    86%
    370
    85.6%
    Not Permitted
    8
    3.7%
    6
    2.8%
    14
    3.2%
    Other
    15
    6.9%
    14
    6.5%
    29
    6.7%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    38
    17.4%
    32
    15%
    70
    16.2%
    Not Hispanic or Latino
    170
    78%
    173
    80.8%
    343
    79.4%
    Not Permitted
    10
    4.6%
    9
    4.2%
    19
    4.4%
    Region of Enrollment (Count of Participants)
    Colombia
    5
    2.3%
    6
    2.8%
    11
    2.5%
    Romania
    15
    6.9%
    13
    6.1%
    28
    6.5%
    Hungary
    11
    5%
    15
    7%
    26
    6%
    United States
    47
    21.6%
    59
    27.6%
    106
    24.5%
    Czechia
    10
    4.6%
    5
    2.3%
    15
    3.5%
    United Kingdom
    5
    2.3%
    6
    2.8%
    11
    2.5%
    Spain
    27
    12.4%
    28
    13.1%
    55
    12.7%
    Turkey
    17
    7.8%
    18
    8.4%
    35
    8.1%
    Belgium
    2
    0.9%
    3
    1.4%
    5
    1.2%
    Poland
    13
    6%
    11
    5.1%
    24
    5.6%
    Italy
    8
    3.7%
    6
    2.8%
    14
    3.2%
    Australia
    13
    6%
    18
    8.4%
    31
    7.2%
    Chile
    15
    6.9%
    11
    5.1%
    26
    6%
    France
    10
    4.6%
    3
    1.4%
    13
    3%
    Peru
    4
    1.8%
    4
    1.9%
    8
    1.9%
    Germany
    16
    7.3%
    8
    3.7%
    24
    5.6%
    Type of Cancer (Count of Participants)
    Gastric
    142
    65.1%
    143
    66.8%
    285
    66%
    Gastroesophageal junction
    76
    34.9%
    71
    33.2%
    147
    34%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time interval from the date of randomization to death from any cause.
    Time Frame Andecaliximab + mFOLFOX6 median follow-up at the time of final analysis: 19.43 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 19.45 months

    Outcome Measure Data

    Analysis Population Description
    The Intent-to-Treat (ITT) Analysis Set included all randomized participants.
    Arm/Group Title Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Arm/Group Description Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 135.4 weeks at the time of final analysis. Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 99.7 weeks at the time of final analysis.
    Measure Participants 218 214
    Median (95% Confidence Interval) [months]
    12.52
    11.76
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Andecaliximab + mFOLFOX6, Placebo + mFOLFOX6
    Comments The primary and secondary endpoints were tested sequentially in the following gate-keeping order: the primary OS endpoint, then the secondary PFS endpoint, and finally the secondary ORR endpoint.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5625
    Comments The significance level at final analysis is 0.046 (two-sided). Stratum with < 6 participants or no informative event by combined treatment arms was pooled with the smallest adjacent stratum for stratified analyses.
    Method Log Rank
    Comments p-value was stratified by Eastern Cooperative Oncology Group (ECOG) status, geographic region and primary tumor site.
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.74 to 1.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio (HR) was stratified by ECOG status, geographic region and primary tumor site with treatment arm as the only covariate.
    2. Secondary Outcome
    Title Progression-free Survival (PFS)
    Description PFS was defined as the interval of time from the date of randomization to the earlier of the first documentation of definitive disease progression or death from any cause.
    Time Frame Andecaliximab + mFOLFOX6 median follow-up at the time of the final analysis: 18.64 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 18.74 months

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Analysis Set were analyzed.
    Arm/Group Title Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Arm/Group Description Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 135.4 weeks at the time of final analysis. Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 99.7 weeks at the time of final analysis.
    Measure Participants 218 214
    Median (95% Confidence Interval) [months]
    7.46
    7.06
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Andecaliximab + mFOLFOX6, Placebo + mFOLFOX6
    Comments The primary and secondary endpoints were tested sequentially in the following gate-keeping order: the primary OS endpoint, then the secondary PFS endpoint, and finally the secondary ORR endpoint. PFS was tested only if OS was significant. The P-value is for display only.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1031
    Comments The significance level at final analysis was 0.032 (two-sided). Stratum with < 6 participants or no informative event by combined treatment arms was pooled with the smallest adjacent stratum for stratified analyses.
    Method Log Rank
    Comments p-value was stratified by ECOG status,geographic region and primary tumor site.
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 0.84
    Confidence Interval (2-Sided) 95%
    0.67 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was stratified by ECOG status,geographic region;primary tumor site with treatment arm as a covariate.Stratum with <6 participants or no informative event by combined treatment arms was pooled with smallest adjacent stratum for stratified analyses.
    3. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    Time Frame Up to 135.4 weeks at the time of final analysis

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Analysis Set were analyzed.
    Arm/Group Title Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Arm/Group Description Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 135.4 weeks at the time of the final analysis. Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 99.7 weeks at the time of the final analysis.
    Measure Participants 218 214
    Number (95% Confidence Interval) [percentage of participants]
    50.5
    23.2%
    41.1
    19.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Andecaliximab + mFOLFOX6, Placebo + mFOLFOX6
    Comments The primary and secondary endpoints were tested sequentially in the following gate-keeping order: the primary OS endpoint, then the secondary PFS endpoint, and finally the secondary ORR endpoint. ORR was tested only if OS and PFS were significant.The P-value is for display only.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0493
    Comments The significance level at final analysis was 0.032 (two-sided). Stratum with < 6 participants or no informative event by combined treatment arms was pooled with the smallest adjacent stratum for stratified analyses.
    Method Cochran-Mantel-Haenszel
    Comments p-value was stratified by ECOG status, geographic region and primary tumor site.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.47
    Confidence Interval (2-Sided) 95%
    1.00 to 2.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments OR was stratified by ECOG status, geographic region and primary tumor site. Stratum with < 6 participants or no informative event by combined treatment arms was pooled with the smallest adjacent stratum for stratified analyses.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Andecaliximab + mFOLFOX6, Placebo + mFOLFOX6
    Comments The primary and secondary endpoints were tested sequentially in the following gate-keeping order: the primary OS endpoint, then the secondary PFS endpoint, and finally the secondary ORR endpoint. ORR was tested only if OS and PFS were significant.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ORR Difference
    Estimated Value 9.4
    Confidence Interval (2-Sided) 95%
    0.1 to 18.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 2-sided 95% confidence interval (CI) of difference for ORR between the treatment and placebo is calculated based on stratum-adjusted Cochran-Mantel-Haenszel proportion.
    4. Secondary Outcome
    Title Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
    Description An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. TEAEs are events in a given study period that meet any of the following criteria: Any AE with onset date of on or after andecalizimab/placebo start date and no later than 30 days after permanent discontinuation of all study treatment (andecaliximab/placebo and chemotherapy) or Any AEs with onset date of on or after the andecaliximab/placebo start date and no later than 55 days after permanent discontinuation of andecaliximab/placebo or AEs leading to discontinuation of andecaliximab/placebo.
    Time Frame First dose date up to the last dose date (maximum:161.7 weeks) plus 30 to 55 days

    Outcome Measure Data

    Analysis Population Description
    The Safety Analysis Set included all participants who received at least one dose of andecaliximab/placebo.
    Arm/Group Title Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Arm/Group Description Participants received andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 161.7 weeks. Participants received placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 112.3 weeks.
    Measure Participants 216 210
    Number [percentage of participants]
    99.1
    45.5%
    99.5
    46.5%
    5. Secondary Outcome
    Title Percentage of Participants With Clinically Relevant Treatment-emergent Laboratory Abnormalities
    Description Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 0=None, 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening. Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any post-baseline time point, up to 30 days after the last dose of all study treatment, or 55 days after the last dose of andecaliximab/placebo for participants who permanently discontinued all study treatments. If the relevant baseline laboratory value is missing, then any abnormality of at least Grade 1 was considered treatment-emergent.
    Time Frame First dose date up to the last dose date (maximum: 161.7 weeks) plus 30 to 55 days

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set were analyzed.
    Arm/Group Title Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Arm/Group Description Participants received andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 161.7 weeks. Participants received placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 112.3 weeks.
    Measure Participants 216 210
    Hematology
    94.4
    43.3%
    89.5
    41.8%
    Serum Chemistry
    91.7
    42.1%
    92.9
    43.4%
    Coagulation
    7.4
    3.4%
    3.3
    1.5%

    Adverse Events

    Time Frame All-Cause Mortality: First dose date up to 42 months; Adverse Events: First dose date up to the last dose date (maximum: 161.7 weeks) plus 30 to 55 days
    Adverse Event Reporting Description All-Cause Mortality:The Intent-to-Treat Analysis Set included all randomized participants.Serious Adverse Events and Other Adverse Events: The Safety Analysis Set included all participants who received at least one dose of andecaliximab/placebo.
    Arm/Group Title Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Arm/Group Description Participants received andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 161.7 weeks. Participants received placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 112.3 weeks.
    All Cause Mortality
    Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 174/218 (79.8%) 168/214 (78.5%)
    Serious Adverse Events
    Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 103/216 (47.7%) 108/210 (51.4%)
    Blood and lymphatic system disorders
    Anaemia 3/216 (1.4%) 2/210 (1%)
    Disseminated intravascular coagulation 1/216 (0.5%) 0/210 (0%)
    Febrile bone marrow aplasia 0/216 (0%) 1/210 (0.5%)
    Febrile neutropenia 6/216 (2.8%) 5/210 (2.4%)
    Neutropenia 4/216 (1.9%) 4/210 (1.9%)
    Thrombocytopenia 2/216 (0.9%) 1/210 (0.5%)
    Cardiac disorders
    Acute myocardial infarction 1/216 (0.5%) 0/210 (0%)
    Atrial fibrillation 1/216 (0.5%) 1/210 (0.5%)
    Atrioventricular block second degree 1/216 (0.5%) 0/210 (0%)
    Cardiac arrest 1/216 (0.5%) 3/210 (1.4%)
    Cardio-respiratory arrest 2/216 (0.9%) 1/210 (0.5%)
    Cardiovascular disorder 1/216 (0.5%) 0/210 (0%)
    Pericardial effusion 1/216 (0.5%) 0/210 (0%)
    Pericarditis 0/216 (0%) 1/210 (0.5%)
    Gastrointestinal disorders
    Abdominal pain 7/216 (3.2%) 8/210 (3.8%)
    Abdominal pain lower 1/216 (0.5%) 0/210 (0%)
    Abdominal pain upper 2/216 (0.9%) 2/210 (1%)
    Colitis 2/216 (0.9%) 0/210 (0%)
    Constipation 3/216 (1.4%) 2/210 (1%)
    Diarrhoea 3/216 (1.4%) 5/210 (2.4%)
    Duodenal ulcer perforation 1/216 (0.5%) 0/210 (0%)
    Dysphagia 3/216 (1.4%) 3/210 (1.4%)
    Gastric haemorrhage 1/216 (0.5%) 2/210 (1%)
    Gastric perforation 0/216 (0%) 1/210 (0.5%)
    Gastric stenosis 0/216 (0%) 1/210 (0.5%)
    Gastrointestinal haemorrhage 6/216 (2.8%) 4/210 (1.9%)
    Gastrointestinal obstruction 1/216 (0.5%) 0/210 (0%)
    Gastrointestinal perforation 1/216 (0.5%) 0/210 (0%)
    Gastrointestinal toxicity 1/216 (0.5%) 0/210 (0%)
    Haematemesis 1/216 (0.5%) 0/210 (0%)
    Ileus 1/216 (0.5%) 1/210 (0.5%)
    Impaired gastric emptying 1/216 (0.5%) 0/210 (0%)
    Incarcerated inguinal hernia 0/216 (0%) 1/210 (0.5%)
    Intestinal obstruction 1/216 (0.5%) 4/210 (1.9%)
    Intestinal pseudo-obstruction 0/216 (0%) 1/210 (0.5%)
    Large intestinal obstruction 1/216 (0.5%) 0/210 (0%)
    Melaena 2/216 (0.9%) 1/210 (0.5%)
    Nausea 4/216 (1.9%) 4/210 (1.9%)
    Obstruction gastric 3/216 (1.4%) 6/210 (2.9%)
    Oesophageal perforation 1/216 (0.5%) 0/210 (0%)
    Oesophageal stenosis 0/216 (0%) 1/210 (0.5%)
    Oesophagitis 1/216 (0.5%) 1/210 (0.5%)
    Pancreatitis acute 2/216 (0.9%) 0/210 (0%)
    Small intestinal obstruction 2/216 (0.9%) 0/210 (0%)
    Upper gastrointestinal haemorrhage 1/216 (0.5%) 4/210 (1.9%)
    Vomiting 11/216 (5.1%) 8/210 (3.8%)
    General disorders
    Chest pain 1/216 (0.5%) 2/210 (1%)
    Death 4/216 (1.9%) 1/210 (0.5%)
    Fatigue 0/216 (0%) 2/210 (1%)
    General physical health deterioration 4/216 (1.9%) 3/210 (1.4%)
    Inflammation 1/216 (0.5%) 0/210 (0%)
    Mucosal inflammation 0/216 (0%) 1/210 (0.5%)
    Non-cardiac chest pain 1/216 (0.5%) 0/210 (0%)
    Pain 1/216 (0.5%) 0/210 (0%)
    Pyrexia 3/216 (1.4%) 4/210 (1.9%)
    Hepatobiliary disorders
    Acute on chronic liver failure 1/216 (0.5%) 0/210 (0%)
    Cholangitis 1/216 (0.5%) 0/210 (0%)
    Cholangitis acute 0/216 (0%) 1/210 (0.5%)
    Cholecystitis 1/216 (0.5%) 0/210 (0%)
    Cholecystitis acute 1/216 (0.5%) 0/210 (0%)
    Hepatic failure 1/216 (0.5%) 0/210 (0%)
    Hyperbilirubinaemia 0/216 (0%) 2/210 (1%)
    Jaundice cholestatic 1/216 (0.5%) 0/210 (0%)
    Immune system disorders
    Anaphylactic reaction 0/216 (0%) 1/210 (0.5%)
    Drug hypersensitivity 0/216 (0%) 1/210 (0.5%)
    Infections and infestations
    Anal abscess 0/216 (0%) 1/210 (0.5%)
    Appendicitis 0/216 (0%) 1/210 (0.5%)
    Cellulitis 1/216 (0.5%) 0/210 (0%)
    Diarrhoea infectious 0/216 (0%) 1/210 (0.5%)
    Diverticulitis 1/216 (0.5%) 0/210 (0%)
    Influenza 2/216 (0.9%) 1/210 (0.5%)
    Lower respiratory tract infection 1/216 (0.5%) 0/210 (0%)
    Neutropenic sepsis 1/216 (0.5%) 0/210 (0%)
    Oesophageal candidiasis 0/216 (0%) 1/210 (0.5%)
    Pneumonia 7/216 (3.2%) 5/210 (2.4%)
    Pneumonia necrotising 0/216 (0%) 1/210 (0.5%)
    Postoperative wound infection 1/216 (0.5%) 0/210 (0%)
    Pyelonephritis acute 0/216 (0%) 1/210 (0.5%)
    Respiratory tract infection 0/216 (0%) 1/210 (0.5%)
    Sepsis 2/216 (0.9%) 4/210 (1.9%)
    Septic shock 0/216 (0%) 2/210 (1%)
    Staphylococcal infection 0/216 (0%) 1/210 (0.5%)
    Upper respiratory tract infection 1/216 (0.5%) 0/210 (0%)
    Urinary tract infection 4/216 (1.9%) 1/210 (0.5%)
    Urosepsis 0/216 (0%) 1/210 (0.5%)
    Vascular device infection 0/216 (0%) 1/210 (0.5%)
    Viral infection 1/216 (0.5%) 0/210 (0%)
    Injury, poisoning and procedural complications
    Accidental overdose 0/216 (0%) 1/210 (0.5%)
    Anastomotic ulcer 1/216 (0.5%) 0/210 (0%)
    Fall 1/216 (0.5%) 1/210 (0.5%)
    Fibula fracture 1/216 (0.5%) 0/210 (0%)
    Hip fracture 1/216 (0.5%) 1/210 (0.5%)
    Humerus fracture 0/216 (0%) 1/210 (0.5%)
    Meniscus injury 1/216 (0.5%) 0/210 (0%)
    Rib fracture 0/216 (0%) 1/210 (0.5%)
    Road traffic accident 1/216 (0.5%) 0/210 (0%)
    Spinal fracture 1/216 (0.5%) 0/210 (0%)
    Subcutaneous haematoma 1/216 (0.5%) 0/210 (0%)
    Tibia fracture 1/216 (0.5%) 0/210 (0%)
    Vascular access complication 0/216 (0%) 1/210 (0.5%)
    Investigations
    Alanine aminotransferase increased 1/216 (0.5%) 0/210 (0%)
    Aspartate aminotransferase increased 2/216 (0.9%) 0/210 (0%)
    Blood bilirubin increased 0/216 (0%) 1/210 (0.5%)
    Body temperature increased 0/216 (0%) 1/210 (0.5%)
    Electrocardiogram QT prolonged 1/216 (0.5%) 0/210 (0%)
    General physical condition abnormal 1/216 (0.5%) 0/210 (0%)
    Haemoglobin decreased 1/216 (0.5%) 0/210 (0%)
    Neutrophil count decreased 1/216 (0.5%) 0/210 (0%)
    Occult blood positive 0/216 (0%) 1/210 (0.5%)
    Transaminases increased 1/216 (0.5%) 0/210 (0%)
    Weight decreased 1/216 (0.5%) 0/210 (0%)
    White blood cell count decreased 1/216 (0.5%) 1/210 (0.5%)
    Metabolism and nutrition disorders
    Cachexia 0/216 (0%) 1/210 (0.5%)
    Decreased appetite 0/216 (0%) 1/210 (0.5%)
    Dehydration 3/216 (1.4%) 3/210 (1.4%)
    Failure to thrive 1/216 (0.5%) 0/210 (0%)
    Hypercalcaemia 0/216 (0%) 1/210 (0.5%)
    Hyperglycaemia 1/216 (0.5%) 1/210 (0.5%)
    Hypoglycaemia 0/216 (0%) 1/210 (0.5%)
    Hypokalaemia 1/216 (0.5%) 0/210 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/216 (0%) 1/210 (0.5%)
    Muscular weakness 0/216 (0%) 1/210 (0.5%)
    Neck pain 0/216 (0%) 1/210 (0.5%)
    Osteolysis 0/216 (0%) 1/210 (0.5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 1/216 (0.5%) 1/210 (0.5%)
    Metastases to meninges 0/216 (0%) 1/210 (0.5%)
    Oesophageal carcinoma 0/216 (0%) 1/210 (0.5%)
    Tumour haemorrhage 1/216 (0.5%) 0/210 (0%)
    Tumour necrosis 1/216 (0.5%) 0/210 (0%)
    Nervous system disorders
    Carotid arteriosclerosis 1/216 (0.5%) 0/210 (0%)
    Cerebrovascular accident 1/216 (0.5%) 2/210 (1%)
    Headache 0/216 (0%) 1/210 (0.5%)
    Hydrocephalus 0/216 (0%) 1/210 (0.5%)
    Hypoaesthesia 0/216 (0%) 1/210 (0.5%)
    Neurological decompensation 0/216 (0%) 1/210 (0.5%)
    Peripheral sensory neuropathy 1/216 (0.5%) 0/210 (0%)
    Seizure 0/216 (0%) 1/210 (0.5%)
    Syncope 2/216 (0.9%) 1/210 (0.5%)
    Transient ischaemic attack 0/216 (0%) 1/210 (0.5%)
    Vocal cord paralysis 0/216 (0%) 1/210 (0.5%)
    Product Issues
    Device dislocation 0/216 (0%) 1/210 (0.5%)
    Renal and urinary disorders
    Acute kidney injury 2/216 (0.9%) 2/210 (1%)
    Nephritis 0/216 (0%) 1/210 (0.5%)
    Nephrolithiasis 0/216 (0%) 1/210 (0.5%)
    Renal failure 0/216 (0%) 1/210 (0.5%)
    Urine flow decreased 0/216 (0%) 1/210 (0.5%)
    Reproductive system and breast disorders
    Prostatitis 0/216 (0%) 1/210 (0.5%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/216 (0%) 1/210 (0.5%)
    Acute respiratory failure 1/216 (0.5%) 0/210 (0%)
    Chronic obstructive pulmonary disease 1/216 (0.5%) 0/210 (0%)
    Dyspnoea 4/216 (1.9%) 1/210 (0.5%)
    Pleural effusion 1/216 (0.5%) 1/210 (0.5%)
    Pneumonitis 2/216 (0.9%) 0/210 (0%)
    Pneumothorax 1/216 (0.5%) 1/210 (0.5%)
    Pulmonary embolism 8/216 (3.7%) 13/210 (6.2%)
    Respiratory distress 1/216 (0.5%) 0/210 (0%)
    Respiratory failure 3/216 (1.4%) 1/210 (0.5%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 1/216 (0.5%) 0/210 (0%)
    Swelling face 0/216 (0%) 1/210 (0.5%)
    Vascular disorders
    Arteriosclerosis 0/216 (0%) 1/210 (0.5%)
    Deep vein thrombosis 3/216 (1.4%) 0/210 (0%)
    Embolism 0/216 (0%) 1/210 (0.5%)
    Peripheral venous disease 0/216 (0%) 1/210 (0.5%)
    Poor venous access 3/216 (1.4%) 0/210 (0%)
    Venous thrombosis 0/216 (0%) 1/210 (0.5%)
    Other (Not Including Serious) Adverse Events
    Andecaliximab + mFOLFOX6 Placebo + mFOLFOX6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 209/216 (96.8%) 203/210 (96.7%)
    Blood and lymphatic system disorders
    Anaemia 61/216 (28.2%) 62/210 (29.5%)
    Neutropenia 76/216 (35.2%) 73/210 (34.8%)
    Thrombocytopenia 38/216 (17.6%) 32/210 (15.2%)
    Gastrointestinal disorders
    Abdominal distension 14/216 (6.5%) 14/210 (6.7%)
    Abdominal pain 41/216 (19%) 37/210 (17.6%)
    Abdominal pain upper 19/216 (8.8%) 26/210 (12.4%)
    Ascites 11/216 (5.1%) 13/210 (6.2%)
    Constipation 61/216 (28.2%) 61/210 (29%)
    Diarrhoea 87/216 (40.3%) 88/210 (41.9%)
    Dry mouth 8/216 (3.7%) 12/210 (5.7%)
    Dyspepsia 20/216 (9.3%) 8/210 (3.8%)
    Dysphagia 21/216 (9.7%) 19/210 (9%)
    Flatulence 11/216 (5.1%) 10/210 (4.8%)
    Gastrooesophageal reflux disease 9/216 (4.2%) 14/210 (6.7%)
    Nausea 106/216 (49.1%) 118/210 (56.2%)
    Stomatitis 24/216 (11.1%) 21/210 (10%)
    Vomiting 63/216 (29.2%) 62/210 (29.5%)
    General disorders
    Asthenia 62/216 (28.7%) 52/210 (24.8%)
    Chest pain 7/216 (3.2%) 11/210 (5.2%)
    Fatigue 79/216 (36.6%) 72/210 (34.3%)
    Mucosal inflammation 25/216 (11.6%) 26/210 (12.4%)
    Oedema peripheral 18/216 (8.3%) 20/210 (9.5%)
    Pyrexia 25/216 (11.6%) 18/210 (8.6%)
    Temperature intolerance 12/216 (5.6%) 12/210 (5.7%)
    Infections and infestations
    Upper respiratory tract infection 16/216 (7.4%) 8/210 (3.8%)
    Urinary tract infection 16/216 (7.4%) 11/210 (5.2%)
    Investigations
    Alanine aminotransferase increased 11/216 (5.1%) 12/210 (5.7%)
    Aspartate aminotransferase increased 13/216 (6%) 11/210 (5.2%)
    Blood alkaline phosphatase increased 15/216 (6.9%) 9/210 (4.3%)
    Neutrophil count decreased 30/216 (13.9%) 25/210 (11.9%)
    Platelet count decreased 19/216 (8.8%) 17/210 (8.1%)
    Weight decreased 29/216 (13.4%) 23/210 (11%)
    Metabolism and nutrition disorders
    Decreased appetite 63/216 (29.2%) 72/210 (34.3%)
    Dehydration 16/216 (7.4%) 16/210 (7.6%)
    Hyperglycaemia 13/216 (6%) 6/210 (2.9%)
    Hypoalbuminaemia 12/216 (5.6%) 8/210 (3.8%)
    Hypokalaemia 28/216 (13%) 22/210 (10.5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 14/216 (6.5%) 10/210 (4.8%)
    Back pain 25/216 (11.6%) 20/210 (9.5%)
    Musculoskeletal pain 12/216 (5.6%) 4/210 (1.9%)
    Myalgia 11/216 (5.1%) 4/210 (1.9%)
    Nervous system disorders
    Dizziness 19/216 (8.8%) 26/210 (12.4%)
    Dysaesthesia 15/216 (6.9%) 12/210 (5.7%)
    Dysgeusia 21/216 (9.7%) 15/210 (7.1%)
    Headache 18/216 (8.3%) 15/210 (7.1%)
    Neuropathy peripheral 28/216 (13%) 21/210 (10%)
    Neurotoxicity 10/216 (4.6%) 11/210 (5.2%)
    Paraesthesia 27/216 (12.5%) 24/210 (11.4%)
    Peripheral sensory neuropathy 73/216 (33.8%) 72/210 (34.3%)
    Taste disorder 7/216 (3.2%) 11/210 (5.2%)
    Psychiatric disorders
    Insomnia 27/216 (12.5%) 22/210 (10.5%)
    Respiratory, thoracic and mediastinal disorders
    Cough 25/216 (11.6%) 23/210 (11%)
    Dyspnoea 20/216 (9.3%) 22/210 (10.5%)
    Epistaxis 16/216 (7.4%) 19/210 (9%)
    Hiccups 11/216 (5.1%) 9/210 (4.3%)
    Pulmonary embolism 10/216 (4.6%) 12/210 (5.7%)
    Skin and subcutaneous tissue disorders
    Alopecia 14/216 (6.5%) 16/210 (7.6%)
    Rash 13/216 (6%) 11/210 (5.2%)
    Vascular disorders
    Hypertension 9/216 (4.2%) 11/210 (5.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02545504
    Other Study ID Numbers:
    • GS-US-296-1080
    • 2015-001526-42
    First Posted:
    Sep 10, 2015
    Last Update Posted:
    May 26, 2020
    Last Verified:
    May 1, 2020