Cypress 1: Study of Pegilodecakin (LY3500518) With Pembrolizumab Compared to Pembrolizumab Alone First-line Tx in Participants With Metastatic Non-Small Cell Lung Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT03382899
Collaborator
ARMO BioSciences (Industry)
101
Enrollment
74
Locations
2
Arms
23.6
Actual Duration (Months)
1.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To compare the efficacy of pegilodecakin in combination with pembrolizumab versus pembrolizumab alone in participants with metastatic non-small cell lung cancer as measured by objective response rate.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

This is an open-label, multi-center, randomized, Phase 2 study designed to compare the efficacy and safety of pegilodecakin in combination with pembrolizumab versus pembrolizumab alone in participants with stage IV / metastatic wild type non-small cell lung cancer and tumors with high expression of PD-L1 (> 50%).

Study Design

Study Type:
Interventional
Actual Enrollment :
101 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase 2 Trial of AM0010 in Combination With Pembrolizumab vs. Pembrolizumab Alone as First-Line (1L) Therapy in Patients With Stage IV / Metastatic Wild Type (WT) Non-Small Cell Lung Cancer and Tumors With High Expression of PD-L1 (> 50%)
Actual Study Start Date :
Mar 19, 2018
Actual Primary Completion Date :
Dec 6, 2019
Actual Study Completion Date :
Mar 5, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Pegilodecakin + Pembrolizumab

Participants received pegilodecakin subcutaneously (SQ) at 0.8 milligrams (mg) (≤80 kilograms (kg) body weight) or 1.6 mg (>80 kg body weight) once daily (QD) in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an intravenous (IV) infusion at 200 mg on Day 1 of a 21-day cycle.

Biological: Pegilodecakin
Pegilodecakin plus Pembrolizumab
Other Names:
  • LY3500518
  • AM0010
  • Drug: Pembrolizumab
    Pembrolizumab Alone

    Active Comparator: Pembrolizumab

    Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.

    Drug: Pembrolizumab
    Pembrolizumab Alone

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Who Achieved an Objective Response Rate (ORR) [From Date of Randomization to Progressive Disease, Death from Any cause (Up to 24 Months)]

      ORR defined as the percentage of participants who achieve a CR or PR as assessed by RECIST v.1.1. The ORR is the number of participants with a complete response (CR) or partial response (PR) divided by the number of randomized participants recorded between the date of randomization and the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever comes first. Complete response (CR) is defined as disappearance of all target (and non-target) lesions, and normalization of tumor marker level. Partial response (PR) is defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters.

    Secondary Outcome Measures

    1. Overall Survival (OS) [From Date of Randomization to Death Due to Any Cause (Up to 24 Months)]

      OS is defined as the time from date of randomization to death due to any cause. Participants who were alive at the end of the follow-up period or lost to follow-up were censored on the last date the participant was known to be alive.

    2. Progression Free Survival (PFS) [From Date of Randomization to Progressive Disease (PD) or Death Due to Any Cause (Up to 24 Months)]

      PFS is defined as the time from date of randomization to the earlier of first documentation of disease progression or death due to any cause. Progressive disease (PD) is defined by at least a 20% increase in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters or the presence of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression determined by scans. Participants who did not progress, who discontinued treatment for toxicity or a reason other than documented progression, or who were lost to follow up before documented progression and death or were censored at the date of last adequate tumor assessment, participants or new anticancer therapy started and not tumor progression or death were censored at the last adequate tumor assessment before the start of new anticancer therapy.

    3. Percentage of Participants Who Achieved a Disease Control Rate (DCR) [From Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 24 Months)]

      DCR is defined as the percentage of participants in the analysis population who have achieved a complete response (CR), partial response (PR) or stable disease (SD) response prior to disease progression. CR is defined as disappearance of all target (and non-target) lesions, and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters. SD is defined as neither sufficient shrinkage of target lesions to qualify for partial response, nor sufficient increase to qualify for progressive disease, taking as reference the baseline sum of longest diameters.

    4. Duration of Response (DOR) [From Date of Response to Death Due to Any Cause (Up to 24 Months)]

      DOR is defined as the time from the earliest date of qualifying response until earliest date of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Duration of response was analyzed in participants who had CR or PR. Duration of response was censored on the date of the last tumor assessment on trial for participants who did not have objective tumor progression and who did not die due to any cause while on trial. For participants who discontinued participation in the trial or discontinued from tumor scan assessments before disease progression, the duration of response was censored at the date of the last tumor assessment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Participants must have histologically or cytologically confirmed WT NSCLC that is stage IV / metastatic or recurrent

    2. Participants with tumor tissue high expression of PD-L1 as defined by Tumor Proportion Score (TPS) ≥ 50%

    3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    4. Participants with measurable disease by spiral CT or MRI per RECIST v.1.1 criteria.

    5. Participants that have completed prior radiotherapy or radiosurgery at least 2 weeks prior to randomization.

    6. Participants must be naïve to therapy for the advanced stage of the disease. Previous neoadjuvant or adjuvant therapy is allowed for participants who successfully underwent complete radical surgery and ONLY if the last treatment was administered more than 12 months prior to the start of the trial treatment

    Exclusion Criteria:
    1. Participants with active central nervous system (CNS) metastases or carcinomatous meningitis

    2. Participants with any serious or uncontrolled medical disorder or active infection with the hepatitis virus or the human immunodeficiency virus (HIV)

    3. Participants with Grade 1 (NCI-CTCAE v.4.03) toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue prior to randomization

    4. Participants that have received pembrolizumab

    5. Participants with a history of severe hypersensitivity reactions to monoclonal antibodies

    6. Pregnant or lactating women

    7. Participants receiving any investigational agent within 28 days of first administration of trial treatment

    8. Participants that have received therapy with anti-tumor vaccines or other immunostimulatory antitumor agents

    9. Participants that have received therapy with anti-PD-1, anti-PD-L1, anti-PD-L-2, anti-CD-137, and/or anti CTLA-4 antibodies

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1CCI - Clearview Cancer InstituteHuntsvilleAlabamaUnited States35805
    2Arizona Oncology Associates, P.C.TempeArizonaUnited States85284
    3Beverly Hills Cancer CenterBeverly HillsCaliforniaUnited States90211
    4St. Joseph Heritage Medical GroupFullertonCaliforniaUnited States92835
    5Glendale Adventist Medical CenterLos AngelesCaliforniaUnited States90017
    6Redlands Community HospitalRedlandsCaliforniaUnited States92373
    7Redwood Regional Oncology CenterSanta RosaCaliforniaUnited States95403
    8The Oncology Institute of Hope and InnovationWhittierCaliforniaUnited States90602
    9Memorial HospitalColorado SpringsColoradoUnited States80909
    10Kaiser Permanente Oncology ClinicDenverColoradoUnited States80205
    11Rocky Mountain Cancer CenterLone TreeColoradoUnited States80124
    12Veterans Affairs Connecticut Healthcare SystemWest HavenConnecticutUnited States06516-2770
    13Medical Oncology Hematolgy Consultants, PANewarkDelawareUnited States19713
    14Lynn Cancer Institute Ctr for Hem-OncBoca RatonFloridaUnited States33486
    15Memorial Cancer InstitutePembroke PinesFloridaUnited States33028
    16SCRI- Florida Cancer SpecialistsTallahasseeFloridaUnited States32308
    17Tallahassee Memorial Cancer CenterTallahasseeFloridaUnited States32308
    18Florida Cancer Specialists EastWest Palm BeachFloridaUnited States33401
    19Northeast Georgia Cancer Care, LLCAthensGeorgiaUnited States30607
    20Pacific Diabetes & Endocrine CenterHonoluluHawaiiUnited States96813
    21AMITA Health Cancer Institute & Outpatient CenterHinsdaleIllinoisUnited States60521
    22Orchard Healthcare Research IncSkokieIllinoisUnited States60077
    23Goshen Health SystemGoshenIndianaUnited States46526
    24University of IowaIowa CityIowaUnited States52242-1009
    25Covenant ClinicWaterlooIowaUnited States50702
    26Menorah Medical CenterOverland ParkKansasUnited States66209
    27Baptist Health Medical GroupLexingtonKentuckyUnited States40503
    28Norton Cancer InstituteLouisvilleKentuckyUnited States40202
    29MedStar Research InstituteBaltimoreMarylandUnited States21237
    30Maryland Oncology Hematology, P.A.ColumbiaMarylandUnited States21044
    31Frederick Memorial HospitalFrederickMarylandUnited States21701
    32St. Joseph Mercy HospitalAnn ArborMichiganUnited States48106
    33Henry Ford Hospital DetroitDetroitMichiganUnited States48202
    34Sparrow Health SystemLansingMichiganUnited States48912
    35Minnesota Oncology/Hematology PAMinneapolisMinnesotaUnited States55404
    36University of Minnesota HospitalMinneapolisMinnesotaUnited States55455
    37Hattiesburg ClinicHattiesburgMississippiUnited States39401
    38St John's Mercy Medical CenterSaint LouisMissouriUnited States63141
    39Nebraska Hematology-OncologyLincolnNebraskaUnited States68506
    40Morristown Medical CenterMorristownNew JerseyUnited States07962
    41The Valley Hospital - Luckow PavilionWestwoodNew JerseyUnited States07675
    42Clinical Research Alliance, Inc.Lake SuccessNew YorkUnited States11042
    43Winthrop University HospitalMineolaNew YorkUnited States11501
    44Stony Brook University Medical CenterStony BrookNew YorkUnited States11794
    45DJL Clinical Research, PLLCCharlotteNorth CarolinaUnited States28207
    46Southeastern Medical Oncology CenterJacksonvilleNorth CarolinaUnited States28546
    47Gabrail Cancer CenterCantonOhioUnited States44718
    48Christ HospitalCincinnatiOhioUnited States45219
    49University of Toledo Medical CenterToledoOhioUnited States43614-2598
    50The Toledo ClinicToledoOhioUnited States43623
    51Oncology Associates of OregonEugeneOregonUnited States97401
    52Charleston Hematology Oncology AssociatesCharlestonSouth CarolinaUnited States29414
    53Avera Cancer InstituteSioux FallsSouth DakotaUnited States57105
    54Chattanooga Oncology Hematology AssociatesChattanoogaTennesseeUnited States37404
    55Thompson Cancer Survival CenterKnoxvilleTennesseeUnited States37916
    56Sarah Cannon Research Institute SCRINashvilleTennesseeUnited States37203
    57Texas Cancer Center (Abilene)AbileneTexasUnited States79606
    58Mamie McFaddin Ward Cancer CenterBeaumontTexasUnited States77702
    59Texas Oncology - Dallas Presbyterian HospitalDallasTexasUnited States75231
    60Texas Oncology-Baylor Charles A. Sammons Cancer CenterDallasTexasUnited States75246
    61Texas Oncology-Memorial CityHoustonTexasUnited States77024
    62Millennium OncologyHoustonTexasUnited States77090
    63Joe Arrington Cancer CenterLubbockTexasUnited States79410
    64Texas Oncology - Midland Allison Cancer CenterMidlandTexasUnited States79701
    65Texas Oncology-ShermanShermanTexasUnited States75090-0504
    66US OncologyThe WoodlandsTexasUnited States77380
    67Texas Oncology - TylerTylerTexasUnited States75702
    68Texas Oncology-Deke Slayton Cancer CenterWebsterTexasUnited States77598-4219
    69Texas Oncology-Wichital Falls Texoma Cancer CenterWichita FallsTexasUnited States76310
    70Fairfax Northern Virginia Hematology Oncology, PCFairfaxVirginiaUnited States22031
    71Oncology and Hematology Associates of Southwest Virginia IncRoanokeVirginiaUnited States24014
    72Shenandoah Oncology, P.C.WinchesterVirginiaUnited States22601
    73MultiCare Regional Cancer Center - AuburnTacomaWashingtonUnited States98002
    74The Richland HospitalWaukeshaWisconsinUnited States53188

    Sponsors and Collaborators

    • Eli Lilly and Company
    • ARMO BioSciences

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT03382899
    Other Study ID Numbers:
    • 17160
    • J1L-AM-JZGC
    • AM0010-201
    First Posted:
    Dec 26, 2017
    Last Update Posted:
    Jan 20, 2021
    Last Verified:
    Jul 1, 2020
    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailParticipants that had a recorded death on study or are alive and being followed at the end of the trial but off treatment are considered as completed group
    Arm/Group TitlePegilodecakin + PembrolizumabPembrolizumab
    Arm/Group DescriptionParticipants received pegilodecakin subcutaneously (SQ) at 0.8 milligrams (mg) (≤80 kilograms (kg) body weight) or 1.6 mg (>80 kg body weight) once daily (QD) in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an intravenous (IV) infusion at 200 mg on Day 1 of a 21-day cycle.Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.
    Period Title: Overall Study
    STARTED5150
    Received at Least 1 Dose of Study Drug5048
    COMPLETED2015
    NOT COMPLETED3135

    Baseline Characteristics

    Arm/Group TitlePegilodecakin + PembrolizumabPebrolizumabTotal
    Arm/Group DescriptionParticipants received pegilodecakin SQ at 0.8 mg (≤80 kg body weight) or 1.6 mg (>80 kg body weight) QD in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an IV infusion at 200 mg on Day 1 of a 21-day cycle.Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.Total of all reporting groups
    Overall Participants5150101
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    67.5
    (7.7)
    67.1
    (9.0)
    67.3
    (8.3)
    Sex: Female, Male (Count of Participants)
    Female
    23
    45.1%
    18
    36%
    41
    40.6%
    Male
    28
    54.9%
    32
    64%
    60
    59.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    5.9%
    2
    4%
    5
    5%
    Not Hispanic or Latino
    40
    78.4%
    47
    94%
    87
    86.1%
    Unknown or Not Reported
    8
    15.7%
    1
    2%
    9
    8.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    3
    6%
    3
    3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    6
    11.8%
    4
    8%
    10
    9.9%
    White
    39
    76.5%
    38
    76%
    77
    76.2%
    More than one race
    3
    5.9%
    4
    8%
    7
    6.9%
    Unknown or Not Reported
    3
    5.9%
    1
    2%
    4
    4%
    Region of Enrollment (Count of Participants)
    United States
    51
    100%
    50
    100%
    101
    100%

    Outcome Measures

    1. Primary Outcome
    TitlePercentage of Participants Who Achieved an Objective Response Rate (ORR)
    DescriptionORR defined as the percentage of participants who achieve a CR or PR as assessed by RECIST v.1.1. The ORR is the number of participants with a complete response (CR) or partial response (PR) divided by the number of randomized participants recorded between the date of randomization and the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever comes first. Complete response (CR) is defined as disappearance of all target (and non-target) lesions, and normalization of tumor marker level. Partial response (PR) is defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters.
    Time FrameFrom Date of Randomization to Progressive Disease, Death from Any cause (Up to 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who had adequate baseline and at least 1 post-baseline tumor assessments.
    Arm/Group TitlePegilodecakin + PembrolizumabPembrolizumab
    Arm/Group DescriptionParticipants received pegilodecakin SQ at 0.8 mg (≤80 kg body weight) or 1.6 mg (>80 kg body weight) QD in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an IV infusion at 200 mg on Day 1 of a 21-day cycle.Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.
    Measure Participants5150
    Number (95% Confidence Interval) [percentage of participants]
    47.1
    92.4%
    44.0
    88%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pegilodecakin + Pembrolizumab, Pembrolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.7626
    Comments
    MethodCochran-Mantel-Haenszel
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value1.1
    Confidence Interval (2-Sided) 95%
    0.5 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation CommentsOdds Ratio stratified by histology type, squamous versus non-squamous based on interactive web response system (IWRS). 95% Confidence intervals (CIs) were estimated using the Clopper-Pearson method.
    2. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS is defined as the time from date of randomization to death due to any cause. Participants who were alive at the end of the follow-up period or lost to follow-up were censored on the last date the participant was known to be alive.
    Time FrameFrom Date of Randomization to Death Due to Any Cause (Up to 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Censored participants in the Pegilodecakin + Pembrolizumab arm is 32 and the Pembrolizumab arm is 39.
    Arm/Group TitlePegilodecakin + PembrolizumabPembrolizumab
    Arm/Group DescriptionParticipants received pegilodecakin SQ at 0.8 mg (≤80 kg body weight) or 1.6 mg (>80 kg body weight) QD in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an IV infusion at 200 mg on Day 1 of a 21-day cycle.Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.
    Measure Participants5150
    Median (95% Confidence Interval) [Months]
    16.33
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pegilodecakin + Pembrolizumab, Pembrolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.263
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.530
    Confidence Interval (2-Sided) 95%
    0.722 to 3.243
    Parameter Dispersion Type:
    Value:
    Estimation CommentsHazard Ratio stratified by histology type, squamous versus non-squamous based on IWRS. 95% CIs were estimated using the methods of Brookmeyer and Crowley, and Greenwood, respectively.
    3. Secondary Outcome
    TitleProgression Free Survival (PFS)
    DescriptionPFS is defined as the time from date of randomization to the earlier of first documentation of disease progression or death due to any cause. Progressive disease (PD) is defined by at least a 20% increase in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters or the presence of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression determined by scans. Participants who did not progress, who discontinued treatment for toxicity or a reason other than documented progression, or who were lost to follow up before documented progression and death or were censored at the date of last adequate tumor assessment, participants or new anticancer therapy started and not tumor progression or death were censored at the last adequate tumor assessment before the start of new anticancer therapy.
    Time FrameFrom Date of Randomization to Progressive Disease (PD) or Death Due to Any Cause (Up to 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Censored participants in the Pegilodecakin + Pembrolizumab arm is 24 and Pembrolizumab arm is 22.
    Arm/Group TitlePegilodecakin + PembrolizumabPembrolizumab
    Arm/Group DescriptionParticipants received pegilodecakin SQ at 0.8 mg (≤80 kg body weight) or 1.6 mg (>80 kg body weight) QD in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an IV infusion at 200 mg on Day 1 of a 21-day cycle.Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.
    Measure Participants5150
    Median (95% Confidence Interval) [Months]
    6.28
    6.08
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pegilodecakin + Pembrolizumab, Pembrolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.20
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.975
    Confidence Interval (2-Sided) 95%
    0.571 to 1.663
    Parameter Dispersion Type:
    Value:
    Estimation CommentsHazard Ratio stratified by histology type, squamous versus non-squamous based on IWRS. 95% CIs were estimated using the Kaplan-Meier method.
    4. Secondary Outcome
    TitlePercentage of Participants Who Achieved a Disease Control Rate (DCR)
    DescriptionDCR is defined as the percentage of participants in the analysis population who have achieved a complete response (CR), partial response (PR) or stable disease (SD) response prior to disease progression. CR is defined as disappearance of all target (and non-target) lesions, and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters. SD is defined as neither sufficient shrinkage of target lesions to qualify for partial response, nor sufficient increase to qualify for progressive disease, taking as reference the baseline sum of longest diameters.
    Time FrameFrom Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group TitlePegilodecakin + PembrolizumabPembrolizumab
    Arm/Group DescriptionParticipants received pegilodecakin SQ at 0.8 mg (≤80 kg body weight) or 1.6 mg (>80 kg body weight) QD in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an IV infusion at 200 mg on Day 1 of a 21-day cycle.Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.
    Measure Participants5150
    Number (95% Confidence Interval) [percentage of participants]
    62.7
    122.9%
    62.0
    124%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pegilodecakin + Pembrolizumab, Pembrolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.9418
    Comments
    MethodCochran-Mantel-Haenszel
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value1.0
    Confidence Interval (2-Sided) 95%
    0.5 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation CommentsOdds Ratio stratified by histology type, squamous versus non-squamous based on IWRS. 95% CIs were estimated using the Clopper-Pearson method.
    5. Secondary Outcome
    TitleDuration of Response (DOR)
    DescriptionDOR is defined as the time from the earliest date of qualifying response until earliest date of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Duration of response was analyzed in participants who had CR or PR. Duration of response was censored on the date of the last tumor assessment on trial for participants who did not have objective tumor progression and who did not die due to any cause while on trial. For participants who discontinued participation in the trial or discontinued from tumor scan assessments before disease progression, the duration of response was censored at the date of the last tumor assessment.
    Time FrameFrom Date of Response to Death Due to Any Cause (Up to 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group TitlePegilodecakin + PembrolizumabPembrolizumab
    Arm/Group DescriptionParticipants received pegilodecakin SQ at 0.8 mg (≤80 kg body weight) or 1.6 mg (>80 kg body weight) QD in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an IV infusion at 200 mg on Day 1 of a 21-day cycle.Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.
    Measure Participants5150
    Median (95% Confidence Interval) [Months]
    14.23
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pegilodecakin + Pembrolizumab, Pembrolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.8312
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.124
    Confidence Interval (2-Sided) 95%
    0.384 to 3.289
    Parameter Dispersion Type:
    Value:
    Estimation CommentsHazard Ratio stratified by histology type, squamous versus non-squamous based on IWRS. 95% CIs were estimated using the methods of Brookmeyer and Crowley, and Greenwood, respectively.

    Adverse Events

    Time FrameBaseline Up To 24 Months
    Adverse Event Reporting Description All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
    Arm/Group TitlePegilodecakin + PembrolizumabPembrolizumab
    Arm/Group DescriptionParticipants received pegilodecakin SQ at 0.8 mg (≤80 kg body weight) or 1.6 mg (>80 kg body weight) QD in the abdomen, thigh or back of upper arm. Pembrolizumab administered as an IV infusion at 200 mg on Day 1 of a 21-day cycle.Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.
    All Cause Mortality
    Pegilodecakin + PembrolizumabPembrolizumab
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total19/50 (38%) 13/48 (27.1%)
    Serious Adverse Events
    Pegilodecakin + PembrolizumabPembrolizumab
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total28/50 (56%) 25/48 (52.1%)
    Blood and lymphatic system disorders
    Anaemia4/50 (8%) 41/48 (2.1%) 1
    Thrombocytopenia0/50 (0%) 01/48 (2.1%) 1
    Cardiac disorders
    Cardiac arrest0/50 (0%) 01/48 (2.1%) 1
    Cardiac failure congestive1/50 (2%) 10/48 (0%) 0
    Cardio-respiratory arrest1/50 (2%) 10/48 (0%) 0
    Pericardial effusion0/50 (0%) 01/48 (2.1%) 1
    Pericarditis0/50 (0%) 01/48 (2.1%) 1
    Tachycardia0/50 (0%) 01/48 (2.1%) 1
    Endocrine disorders
    Adrenal insufficiency1/50 (2%) 11/48 (2.1%) 1
    Hyperthyroidism1/50 (2%) 10/48 (0%) 0
    Gastrointestinal disorders
    Abdominal distension1/50 (2%) 20/48 (0%) 0
    Abdominal pain upper1/50 (2%) 10/48 (0%) 0
    Colitis microscopic1/50 (2%) 10/48 (0%) 0
    Diarrhoea0/50 (0%) 02/48 (4.2%) 2
    Diverticular perforation1/50 (2%) 10/48 (0%) 0
    Gastric haemorrhage1/50 (2%) 10/48 (0%) 0
    Gastritis1/50 (2%) 10/48 (0%) 0
    Vomiting1/50 (2%) 10/48 (0%) 0
    General disorders
    Fatigue1/50 (2%) 12/48 (4.2%) 2
    Localised oedema0/50 (0%) 01/48 (2.1%) 1
    Non-cardiac chest pain1/50 (2%) 10/48 (0%) 0
    Pyrexia1/50 (2%) 10/48 (0%) 0
    Systemic inflammatory response syndrome1/50 (2%) 10/48 (0%) 0
    Hepatobiliary disorders
    Autoimmune hepatitis0/50 (0%) 01/48 (2.1%) 1
    Drug-induced liver injury1/50 (2%) 10/48 (0%) 0
    Infections and infestations
    Pneumonia9/50 (18%) 106/48 (12.5%) 6
    Sepsis5/50 (10%) 60/48 (0%) 0
    Septic shock1/50 (2%) 10/48 (0%) 0
    Streptococcal bacteraemia1/50 (2%) 10/48 (0%) 0
    Injury, poisoning and procedural complications
    Ankle fracture0/50 (0%) 01/48 (2.1%) 1
    Clavicle fracture0/50 (0%) 01/48 (2.1%) 1
    Fibula fracture0/50 (0%) 01/48 (2.1%) 1
    Overdose0/50 (0%) 01/48 (2.1%) 1
    Spinal compression fracture1/50 (2%) 10/48 (0%) 0
    Spinal fracture1/50 (2%) 10/48 (0%) 0
    Investigations
    Alanine aminotransferase increased1/50 (2%) 10/48 (0%) 0
    Aspartate aminotransferase increased1/50 (2%) 20/48 (0%) 0
    Blood bilirubin increased2/50 (4%) 20/48 (0%) 0
    Metabolism and nutrition disorders
    Dehydration5/50 (10%) 70/48 (0%) 0
    Failure to thrive1/50 (2%) 11/48 (2.1%) 1
    Hyperglycaemia1/50 (2%) 10/48 (0%) 0
    Hypoalbuminaemia0/50 (0%) 01/48 (2.1%) 1
    Hypokalaemia1/50 (2%) 10/48 (0%) 0
    Hyponatraemia3/50 (6%) 31/48 (2.1%) 1
    Musculoskeletal and connective tissue disorders
    Myalgia0/50 (0%) 01/48 (2.1%) 1
    Nervous system disorders
    Brain oedema1/50 (2%) 10/48 (0%) 0
    Cerebrovascular accident1/50 (2%) 11/48 (2.1%) 1
    Dizziness0/50 (0%) 02/48 (4.2%) 2
    Ischaemic cerebral infarction0/50 (0%) 01/48 (2.1%) 1
    Loss of consciousness0/50 (0%) 01/48 (2.1%) 1
    Myelopathy0/50 (0%) 01/48 (2.1%) 1
    Psychiatric disorders
    Confusional state1/50 (2%) 11/48 (2.1%) 1
    Renal and urinary disorders
    Acute kidney injury2/50 (4%) 20/48 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure1/50 (2%) 11/48 (2.1%) 1
    Chronic obstructive pulmonary disease0/50 (0%) 01/48 (2.1%) 1
    Dyspnoea3/50 (6%) 54/48 (8.3%) 5
    Hypoxia0/50 (0%) 03/48 (6.3%) 3
    Pleural effusion0/50 (0%) 03/48 (6.3%) 4
    Pneumonitis2/50 (4%) 22/48 (4.2%) 2
    Pneumothorax1/50 (2%) 10/48 (0%) 0
    Pulmonary embolism2/50 (4%) 21/48 (2.1%) 1
    Pulmonary hypertension0/50 (0%) 01/48 (2.1%) 1
    Respiratory failure2/50 (4%) 32/48 (4.2%) 3
    Vascular disorders
    Capillary leak syndrome1/50 (2%) 30/48 (0%) 0
    Deep vein thrombosis0/50 (0%) 01/48 (2.1%) 1
    Hypotension3/50 (6%) 30/48 (0%) 0
    Other (Not Including Serious) Adverse Events
    Pegilodecakin + PembrolizumabPembrolizumab
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total48/50 (96%) 48/48 (100%)
    Blood and lymphatic system disorders
    Anaemia30/50 (60%) 9210/48 (20.8%) 18
    Thrombocytopenia14/50 (28%) 285/48 (10.4%) 9
    Cardiac disorders
    Sinus tachycardia4/50 (8%) 41/48 (2.1%) 1
    Tachycardia4/50 (8%) 40/48 (0%) 0
    Endocrine disorders
    Hypothyroidism1/50 (2%) 23/48 (6.3%) 3
    Gastrointestinal disorders
    Abdominal pain3/50 (6%) 32/48 (4.2%) 4
    Constipation5/50 (10%) 616/48 (33.3%) 19
    Diarrhoea12/50 (24%) 2311/48 (22.9%) 16
    Dry mouth5/50 (10%) 53/48 (6.3%) 4
    Dyspepsia1/50 (2%) 14/48 (8.3%) 4
    Dysphagia1/50 (2%) 13/48 (6.3%) 3
    Nausea14/50 (28%) 1610/48 (20.8%) 12
    Stomatitis3/50 (6%) 32/48 (4.2%) 3
    Vomiting3/50 (6%) 35/48 (10.4%) 7
    General disorders
    Asthenia4/50 (8%) 43/48 (6.3%) 3
    Chills7/50 (14%) 81/48 (2.1%) 2
    Fatigue27/50 (54%) 4123/48 (47.9%) 25
    Injection site reaction4/50 (8%) 52/48 (4.2%) 3
    Localised oedema1/50 (2%) 13/48 (6.3%) 3
    Malaise1/50 (2%) 63/48 (6.3%) 3
    Non-cardiac chest pain5/50 (10%) 61/48 (2.1%) 1
    Oedema peripheral9/50 (18%) 910/48 (20.8%) 12
    Pyrexia13/50 (26%) 163/48 (6.3%) 3
    Hepatobiliary disorders
    Hyperbilirubinaemia4/50 (8%) 60/48 (0%) 0
    Infections and infestations
    Pneumonia4/50 (8%) 52/48 (4.2%) 2
    Sinusitis2/50 (4%) 23/48 (6.3%) 3
    Upper respiratory tract infection2/50 (4%) 24/48 (8.3%) 4
    Urinary tract infection7/50 (14%) 94/48 (8.3%) 4
    Injury, poisoning and procedural complications
    Fall3/50 (6%) 36/48 (12.5%) 7
    Investigations
    Activated partial thromboplastin time prolonged0/50 (0%) 03/48 (6.3%) 3
    Alanine aminotransferase increased4/50 (8%) 92/48 (4.2%) 3
    Aspartate aminotransferase increased5/50 (10%) 84/48 (8.3%) 7
    Blood alkaline phosphatase increased4/50 (8%) 51/48 (2.1%) 1
    Blood bilirubin increased3/50 (6%) 51/48 (2.1%) 4
    Blood creatinine increased6/50 (12%) 152/48 (4.2%) 2
    Blood urea increased0/50 (0%) 03/48 (6.3%) 3
    Platelet count decreased6/50 (12%) 134/48 (8.3%) 9
    Weight decreased5/50 (10%) 68/48 (16.7%) 11
    Metabolism and nutrition disorders
    Decreased appetite19/50 (38%) 2116/48 (33.3%) 16
    Dehydration11/50 (22%) 123/48 (6.3%) 4
    Hyperglycaemia3/50 (6%) 55/48 (10.4%) 9
    Hypoalbuminaemia4/50 (8%) 42/48 (4.2%) 2
    Hypokalaemia4/50 (8%) 41/48 (2.1%) 1
    Hypomagnesaemia5/50 (10%) 61/48 (2.1%) 1
    Hyponatraemia5/50 (10%) 64/48 (8.3%) 7
    Musculoskeletal and connective tissue disorders
    Arthralgia9/50 (18%) 1511/48 (22.9%) 12
    Back pain3/50 (6%) 37/48 (14.6%) 7
    Muscle spasms5/50 (10%) 53/48 (6.3%) 3
    Muscular weakness4/50 (8%) 65/48 (10.4%) 5
    Musculoskeletal chest pain3/50 (6%) 43/48 (6.3%) 4
    Myalgia5/50 (10%) 121/48 (2.1%) 1
    Pain in extremity1/50 (2%) 23/48 (6.3%) 3
    Nervous system disorders
    Dizziness7/50 (14%) 83/48 (6.3%) 3
    Dysgeusia4/50 (8%) 42/48 (4.2%) 2
    Headache9/50 (18%) 106/48 (12.5%) 10
    Psychiatric disorders
    Anxiety6/50 (12%) 62/48 (4.2%) 3
    Depression4/50 (8%) 44/48 (8.3%) 4
    Insomnia6/50 (12%) 96/48 (12.5%) 6
    Renal and urinary disorders
    Acute kidney injury3/50 (6%) 30/48 (0%) 0
    Reproductive system and breast disorders
    Vaginal discharge0/22 (0%) 01/18 (5.6%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough11/50 (22%) 1313/48 (27.1%) 16
    Dyspnoea16/50 (32%) 2813/48 (27.1%) 24
    Haemoptysis2/50 (4%) 24/48 (8.3%) 5
    Nasal congestion2/50 (4%) 24/48 (8.3%) 5
    Productive cough3/50 (6%) 31/48 (2.1%) 1
    Upper-airway cough syndrome0/50 (0%) 04/48 (8.3%) 4
    Wheezing1/50 (2%) 13/48 (6.3%) 3
    Skin and subcutaneous tissue disorders
    Dermatitis4/50 (8%) 51/48 (2.1%) 1
    Dry skin3/50 (6%) 38/48 (16.7%) 8
    Night sweats6/50 (12%) 60/48 (0%) 0
    Pruritus8/50 (16%) 88/48 (16.7%) 11
    Rash13/50 (26%) 217/48 (14.6%) 7
    Rash maculo-papular3/50 (6%) 47/48 (14.6%) 12
    Vascular disorders
    Deep vein thrombosis0/50 (0%) 03/48 (6.3%) 4
    Hypertension0/50 (0%) 03/48 (6.3%) 3
    Hypotension13/50 (26%) 173/48 (6.3%) 8

    Limitations/Caveats

    Study was terminated early after completion of primary analysis; hence, no mature data were available for final analysis.

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 120 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/TitleChief Medical Officer
    OrganizationEli Lilly and Company
    Phone(800) 545-5979
    Emailwww.ClinicalTrials.gov@lilly.com
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT03382899
    Other Study ID Numbers:
    • 17160
    • J1L-AM-JZGC
    • AM0010-201
    First Posted:
    Dec 26, 2017
    Last Update Posted:
    Jan 20, 2021
    Last Verified:
    Jul 1, 2020