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
74
2
23.6
1.4
0.1

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 Disease Intervention/Treatment Phase
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

Arm Intervention/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

    Site City State Country Postal Code
    1 CCI - Clearview Cancer Institute Huntsville Alabama United States 35805
    2 Arizona Oncology Associates, P.C. Tempe Arizona United States 85284
    3 Beverly Hills Cancer Center Beverly Hills California United States 90211
    4 St. Joseph Heritage Medical Group Fullerton California United States 92835
    5 Glendale Adventist Medical Center Los Angeles California United States 90017
    6 Redlands Community Hospital Redlands California United States 92373
    7 Redwood Regional Oncology Center Santa Rosa California United States 95403
    8 The Oncology Institute of Hope and Innovation Whittier California United States 90602
    9 Memorial Hospital Colorado Springs Colorado United States 80909
    10 Kaiser Permanente Oncology Clinic Denver Colorado United States 80205
    11 Rocky Mountain Cancer Center Lone Tree Colorado United States 80124
    12 Veterans Affairs Connecticut Healthcare System West Haven Connecticut United States 06516-2770
    13 Medical Oncology Hematolgy Consultants, PA Newark Delaware United States 19713
    14 Lynn Cancer Institute Ctr for Hem-Onc Boca Raton Florida United States 33486
    15 Memorial Cancer Institute Pembroke Pines Florida United States 33028
    16 SCRI- Florida Cancer Specialists Tallahassee Florida United States 32308
    17 Tallahassee Memorial Cancer Center Tallahassee Florida United States 32308
    18 Florida Cancer Specialists East West Palm Beach Florida United States 33401
    19 Northeast Georgia Cancer Care, LLC Athens Georgia United States 30607
    20 Pacific Diabetes & Endocrine Center Honolulu Hawaii United States 96813
    21 AMITA Health Cancer Institute & Outpatient Center Hinsdale Illinois United States 60521
    22 Orchard Healthcare Research Inc Skokie Illinois United States 60077
    23 Goshen Health System Goshen Indiana United States 46526
    24 University of Iowa Iowa City Iowa United States 52242-1009
    25 Covenant Clinic Waterloo Iowa United States 50702
    26 Menorah Medical Center Overland Park Kansas United States 66209
    27 Baptist Health Medical Group Lexington Kentucky United States 40503
    28 Norton Cancer Institute Louisville Kentucky United States 40202
    29 MedStar Research Institute Baltimore Maryland United States 21237
    30 Maryland Oncology Hematology, P.A. Columbia Maryland United States 21044
    31 Frederick Memorial Hospital Frederick Maryland United States 21701
    32 St. Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    33 Henry Ford Hospital Detroit Detroit Michigan United States 48202
    34 Sparrow Health System Lansing Michigan United States 48912
    35 Minnesota Oncology/Hematology PA Minneapolis Minnesota United States 55404
    36 University of Minnesota Hospital Minneapolis Minnesota United States 55455
    37 Hattiesburg Clinic Hattiesburg Mississippi United States 39401
    38 St John's Mercy Medical Center Saint Louis Missouri United States 63141
    39 Nebraska Hematology-Oncology Lincoln Nebraska United States 68506
    40 Morristown Medical Center Morristown New Jersey United States 07962
    41 The Valley Hospital - Luckow Pavilion Westwood New Jersey United States 07675
    42 Clinical Research Alliance, Inc. Lake Success New York United States 11042
    43 Winthrop University Hospital Mineola New York United States 11501
    44 Stony Brook University Medical Center Stony Brook New York United States 11794
    45 DJL Clinical Research, PLLC Charlotte North Carolina United States 28207
    46 Southeastern Medical Oncology Center Jacksonville North Carolina United States 28546
    47 Gabrail Cancer Center Canton Ohio United States 44718
    48 Christ Hospital Cincinnati Ohio United States 45219
    49 University of Toledo Medical Center Toledo Ohio United States 43614-2598
    50 The Toledo Clinic Toledo Ohio United States 43623
    51 Oncology Associates of Oregon Eugene Oregon United States 97401
    52 Charleston Hematology Oncology Associates Charleston South Carolina United States 29414
    53 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    54 Chattanooga Oncology Hematology Associates Chattanooga Tennessee United States 37404
    55 Thompson Cancer Survival Center Knoxville Tennessee United States 37916
    56 Sarah Cannon Research Institute SCRI Nashville Tennessee United States 37203
    57 Texas Cancer Center (Abilene) Abilene Texas United States 79606
    58 Mamie McFaddin Ward Cancer Center Beaumont Texas United States 77702
    59 Texas Oncology - Dallas Presbyterian Hospital Dallas Texas United States 75231
    60 Texas Oncology-Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    61 Texas Oncology-Memorial City Houston Texas United States 77024
    62 Millennium Oncology Houston Texas United States 77090
    63 Joe Arrington Cancer Center Lubbock Texas United States 79410
    64 Texas Oncology - Midland Allison Cancer Center Midland Texas United States 79701
    65 Texas Oncology-Sherman Sherman Texas United States 75090-0504
    66 US Oncology The Woodlands Texas United States 77380
    67 Texas Oncology - Tyler Tyler Texas United States 75702
    68 Texas Oncology-Deke Slayton Cancer Center Webster Texas United States 77598-4219
    69 Texas Oncology-Wichital Falls Texoma Cancer Center Wichita Falls Texas United States 76310
    70 Fairfax Northern Virginia Hematology Oncology, PC Fairfax Virginia United States 22031
    71 Oncology and Hematology Associates of Southwest Virginia Inc Roanoke Virginia United States 24014
    72 Shenandoah Oncology, P.C. Winchester Virginia United States 22601
    73 MultiCare Regional Cancer Center - Auburn Tacoma Washington United States 98002
    74 The Richland Hospital Waukesha Wisconsin United States 53188

    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 Detail Participants 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 Title Pegilodecakin + Pembrolizumab Pembrolizumab
    Arm/Group Description 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. Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle.
    Period Title: Overall Study
    STARTED 51 50
    Received at Least 1 Dose of Study Drug 50 48
    COMPLETED 20 15
    NOT COMPLETED 31 35

    Baseline Characteristics

    Arm/Group Title Pegilodecakin + Pembrolizumab Pebrolizumab Total
    Arm/Group Description Participants 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 Participants 51 50 101
    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
    Title Percentage of Participants Who Achieved an Objective Response Rate (ORR)
    Description 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.
    Time Frame From 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 Title Pegilodecakin + Pembrolizumab Pembrolizumab
    Arm/Group Description Participants 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 Participants 51 50
    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 Hypothesis p-Value 0.7626
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.1
    Confidence Interval (2-Sided) 95%
    0.5 to 2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds 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
    Title Overall Survival (OS)
    Description 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.
    Time Frame From 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 Title Pegilodecakin + Pembrolizumab Pembrolizumab
    Arm/Group Description Participants 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 Participants 51 50
    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 Hypothesis p-Value 0.263
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.530
    Confidence Interval (2-Sided) 95%
    0.722 to 3.243
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard 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
    Title Progression Free Survival (PFS)
    Description 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.
    Time Frame From 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 Title Pegilodecakin + Pembrolizumab Pembrolizumab
    Arm/Group Description Participants 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 Participants 51 50
    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 Hypothesis p-Value 0.20
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.975
    Confidence Interval (2-Sided) 95%
    0.571 to 1.663
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard Ratio stratified by histology type, squamous versus non-squamous based on IWRS. 95% CIs were estimated using the Kaplan-Meier method.
    4. Secondary Outcome
    Title Percentage of Participants Who Achieved a Disease Control Rate (DCR)
    Description 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.
    Time Frame From 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 Title Pegilodecakin + Pembrolizumab Pembrolizumab
    Arm/Group Description Participants 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 Participants 51 50
    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 Hypothesis p-Value 0.9418
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    0.5 to 2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds Ratio stratified by histology type, squamous versus non-squamous based on IWRS. 95% CIs were estimated using the Clopper-Pearson method.
    5. Secondary Outcome
    Title Duration of Response (DOR)
    Description 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.
    Time Frame From Date of Response to Death Due to Any Cause (Up to 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Pegilodecakin + Pembrolizumab Pembrolizumab
    Arm/Group Description Participants 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 Participants 51 50
    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 Hypothesis p-Value 0.8312
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.124
    Confidence Interval (2-Sided) 95%
    0.384 to 3.289
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard 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 Frame Baseline 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 Title Pegilodecakin + Pembrolizumab Pembrolizumab
    Arm/Group Description Participants 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 + Pembrolizumab Pembrolizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/50 (38%) 13/48 (27.1%)
    Serious Adverse Events
    Pegilodecakin + Pembrolizumab Pembrolizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 28/50 (56%) 25/48 (52.1%)
    Blood and lymphatic system disorders
    Anaemia 4/50 (8%) 4 1/48 (2.1%) 1
    Thrombocytopenia 0/50 (0%) 0 1/48 (2.1%) 1
    Cardiac disorders
    Cardiac arrest 0/50 (0%) 0 1/48 (2.1%) 1
    Cardiac failure congestive 1/50 (2%) 1 0/48 (0%) 0
    Cardio-respiratory arrest 1/50 (2%) 1 0/48 (0%) 0
    Pericardial effusion 0/50 (0%) 0 1/48 (2.1%) 1
    Pericarditis 0/50 (0%) 0 1/48 (2.1%) 1
    Tachycardia 0/50 (0%) 0 1/48 (2.1%) 1
    Endocrine disorders
    Adrenal insufficiency 1/50 (2%) 1 1/48 (2.1%) 1
    Hyperthyroidism 1/50 (2%) 1 0/48 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 1/50 (2%) 2 0/48 (0%) 0
    Abdominal pain upper 1/50 (2%) 1 0/48 (0%) 0
    Colitis microscopic 1/50 (2%) 1 0/48 (0%) 0
    Diarrhoea 0/50 (0%) 0 2/48 (4.2%) 2
    Diverticular perforation 1/50 (2%) 1 0/48 (0%) 0
    Gastric haemorrhage 1/50 (2%) 1 0/48 (0%) 0
    Gastritis 1/50 (2%) 1 0/48 (0%) 0
    Vomiting 1/50 (2%) 1 0/48 (0%) 0
    General disorders
    Fatigue 1/50 (2%) 1 2/48 (4.2%) 2
    Localised oedema 0/50 (0%) 0 1/48 (2.1%) 1
    Non-cardiac chest pain 1/50 (2%) 1 0/48 (0%) 0
    Pyrexia 1/50 (2%) 1 0/48 (0%) 0
    Systemic inflammatory response syndrome 1/50 (2%) 1 0/48 (0%) 0
    Hepatobiliary disorders
    Autoimmune hepatitis 0/50 (0%) 0 1/48 (2.1%) 1
    Drug-induced liver injury 1/50 (2%) 1 0/48 (0%) 0
    Infections and infestations
    Pneumonia 9/50 (18%) 10 6/48 (12.5%) 6
    Sepsis 5/50 (10%) 6 0/48 (0%) 0
    Septic shock 1/50 (2%) 1 0/48 (0%) 0
    Streptococcal bacteraemia 1/50 (2%) 1 0/48 (0%) 0
    Injury, poisoning and procedural complications
    Ankle fracture 0/50 (0%) 0 1/48 (2.1%) 1
    Clavicle fracture 0/50 (0%) 0 1/48 (2.1%) 1
    Fibula fracture 0/50 (0%) 0 1/48 (2.1%) 1
    Overdose 0/50 (0%) 0 1/48 (2.1%) 1
    Spinal compression fracture 1/50 (2%) 1 0/48 (0%) 0
    Spinal fracture 1/50 (2%) 1 0/48 (0%) 0
    Investigations
    Alanine aminotransferase increased 1/50 (2%) 1 0/48 (0%) 0
    Aspartate aminotransferase increased 1/50 (2%) 2 0/48 (0%) 0
    Blood bilirubin increased 2/50 (4%) 2 0/48 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 5/50 (10%) 7 0/48 (0%) 0
    Failure to thrive 1/50 (2%) 1 1/48 (2.1%) 1
    Hyperglycaemia 1/50 (2%) 1 0/48 (0%) 0
    Hypoalbuminaemia 0/50 (0%) 0 1/48 (2.1%) 1
    Hypokalaemia 1/50 (2%) 1 0/48 (0%) 0
    Hyponatraemia 3/50 (6%) 3 1/48 (2.1%) 1
    Musculoskeletal and connective tissue disorders
    Myalgia 0/50 (0%) 0 1/48 (2.1%) 1
    Nervous system disorders
    Brain oedema 1/50 (2%) 1 0/48 (0%) 0
    Cerebrovascular accident 1/50 (2%) 1 1/48 (2.1%) 1
    Dizziness 0/50 (0%) 0 2/48 (4.2%) 2
    Ischaemic cerebral infarction 0/50 (0%) 0 1/48 (2.1%) 1
    Loss of consciousness 0/50 (0%) 0 1/48 (2.1%) 1
    Myelopathy 0/50 (0%) 0 1/48 (2.1%) 1
    Psychiatric disorders
    Confusional state 1/50 (2%) 1 1/48 (2.1%) 1
    Renal and urinary disorders
    Acute kidney injury 2/50 (4%) 2 0/48 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/50 (2%) 1 1/48 (2.1%) 1
    Chronic obstructive pulmonary disease 0/50 (0%) 0 1/48 (2.1%) 1
    Dyspnoea 3/50 (6%) 5 4/48 (8.3%) 5
    Hypoxia 0/50 (0%) 0 3/48 (6.3%) 3
    Pleural effusion 0/50 (0%) 0 3/48 (6.3%) 4
    Pneumonitis 2/50 (4%) 2 2/48 (4.2%) 2
    Pneumothorax 1/50 (2%) 1 0/48 (0%) 0
    Pulmonary embolism 2/50 (4%) 2 1/48 (2.1%) 1
    Pulmonary hypertension 0/50 (0%) 0 1/48 (2.1%) 1
    Respiratory failure 2/50 (4%) 3 2/48 (4.2%) 3
    Vascular disorders
    Capillary leak syndrome 1/50 (2%) 3 0/48 (0%) 0
    Deep vein thrombosis 0/50 (0%) 0 1/48 (2.1%) 1
    Hypotension 3/50 (6%) 3 0/48 (0%) 0
    Other (Not Including Serious) Adverse Events
    Pegilodecakin + Pembrolizumab Pembrolizumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 48/50 (96%) 48/48 (100%)
    Blood and lymphatic system disorders
    Anaemia 30/50 (60%) 92 10/48 (20.8%) 18
    Thrombocytopenia 14/50 (28%) 28 5/48 (10.4%) 9
    Cardiac disorders
    Sinus tachycardia 4/50 (8%) 4 1/48 (2.1%) 1
    Tachycardia 4/50 (8%) 4 0/48 (0%) 0
    Endocrine disorders
    Hypothyroidism 1/50 (2%) 2 3/48 (6.3%) 3
    Gastrointestinal disorders
    Abdominal pain 3/50 (6%) 3 2/48 (4.2%) 4
    Constipation 5/50 (10%) 6 16/48 (33.3%) 19
    Diarrhoea 12/50 (24%) 23 11/48 (22.9%) 16
    Dry mouth 5/50 (10%) 5 3/48 (6.3%) 4
    Dyspepsia 1/50 (2%) 1 4/48 (8.3%) 4
    Dysphagia 1/50 (2%) 1 3/48 (6.3%) 3
    Nausea 14/50 (28%) 16 10/48 (20.8%) 12
    Stomatitis 3/50 (6%) 3 2/48 (4.2%) 3
    Vomiting 3/50 (6%) 3 5/48 (10.4%) 7
    General disorders
    Asthenia 4/50 (8%) 4 3/48 (6.3%) 3
    Chills 7/50 (14%) 8 1/48 (2.1%) 2
    Fatigue 27/50 (54%) 41 23/48 (47.9%) 25
    Injection site reaction 4/50 (8%) 5 2/48 (4.2%) 3
    Localised oedema 1/50 (2%) 1 3/48 (6.3%) 3
    Malaise 1/50 (2%) 6 3/48 (6.3%) 3
    Non-cardiac chest pain 5/50 (10%) 6 1/48 (2.1%) 1
    Oedema peripheral 9/50 (18%) 9 10/48 (20.8%) 12
    Pyrexia 13/50 (26%) 16 3/48 (6.3%) 3
    Hepatobiliary disorders
    Hyperbilirubinaemia 4/50 (8%) 6 0/48 (0%) 0
    Infections and infestations
    Pneumonia 4/50 (8%) 5 2/48 (4.2%) 2
    Sinusitis 2/50 (4%) 2 3/48 (6.3%) 3
    Upper respiratory tract infection 2/50 (4%) 2 4/48 (8.3%) 4
    Urinary tract infection 7/50 (14%) 9 4/48 (8.3%) 4
    Injury, poisoning and procedural complications
    Fall 3/50 (6%) 3 6/48 (12.5%) 7
    Investigations
    Activated partial thromboplastin time prolonged 0/50 (0%) 0 3/48 (6.3%) 3
    Alanine aminotransferase increased 4/50 (8%) 9 2/48 (4.2%) 3
    Aspartate aminotransferase increased 5/50 (10%) 8 4/48 (8.3%) 7
    Blood alkaline phosphatase increased 4/50 (8%) 5 1/48 (2.1%) 1
    Blood bilirubin increased 3/50 (6%) 5 1/48 (2.1%) 4
    Blood creatinine increased 6/50 (12%) 15 2/48 (4.2%) 2
    Blood urea increased 0/50 (0%) 0 3/48 (6.3%) 3
    Platelet count decreased 6/50 (12%) 13 4/48 (8.3%) 9
    Weight decreased 5/50 (10%) 6 8/48 (16.7%) 11
    Metabolism and nutrition disorders
    Decreased appetite 19/50 (38%) 21 16/48 (33.3%) 16
    Dehydration 11/50 (22%) 12 3/48 (6.3%) 4
    Hyperglycaemia 3/50 (6%) 5 5/48 (10.4%) 9
    Hypoalbuminaemia 4/50 (8%) 4 2/48 (4.2%) 2
    Hypokalaemia 4/50 (8%) 4 1/48 (2.1%) 1
    Hypomagnesaemia 5/50 (10%) 6 1/48 (2.1%) 1
    Hyponatraemia 5/50 (10%) 6 4/48 (8.3%) 7
    Musculoskeletal and connective tissue disorders
    Arthralgia 9/50 (18%) 15 11/48 (22.9%) 12
    Back pain 3/50 (6%) 3 7/48 (14.6%) 7
    Muscle spasms 5/50 (10%) 5 3/48 (6.3%) 3
    Muscular weakness 4/50 (8%) 6 5/48 (10.4%) 5
    Musculoskeletal chest pain 3/50 (6%) 4 3/48 (6.3%) 4
    Myalgia 5/50 (10%) 12 1/48 (2.1%) 1
    Pain in extremity 1/50 (2%) 2 3/48 (6.3%) 3
    Nervous system disorders
    Dizziness 7/50 (14%) 8 3/48 (6.3%) 3
    Dysgeusia 4/50 (8%) 4 2/48 (4.2%) 2
    Headache 9/50 (18%) 10 6/48 (12.5%) 10
    Psychiatric disorders
    Anxiety 6/50 (12%) 6 2/48 (4.2%) 3
    Depression 4/50 (8%) 4 4/48 (8.3%) 4
    Insomnia 6/50 (12%) 9 6/48 (12.5%) 6
    Renal and urinary disorders
    Acute kidney injury 3/50 (6%) 3 0/48 (0%) 0
    Reproductive system and breast disorders
    Vaginal discharge 0/22 (0%) 0 1/18 (5.6%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough 11/50 (22%) 13 13/48 (27.1%) 16
    Dyspnoea 16/50 (32%) 28 13/48 (27.1%) 24
    Haemoptysis 2/50 (4%) 2 4/48 (8.3%) 5
    Nasal congestion 2/50 (4%) 2 4/48 (8.3%) 5
    Productive cough 3/50 (6%) 3 1/48 (2.1%) 1
    Upper-airway cough syndrome 0/50 (0%) 0 4/48 (8.3%) 4
    Wheezing 1/50 (2%) 1 3/48 (6.3%) 3
    Skin and subcutaneous tissue disorders
    Dermatitis 4/50 (8%) 5 1/48 (2.1%) 1
    Dry skin 3/50 (6%) 3 8/48 (16.7%) 8
    Night sweats 6/50 (12%) 6 0/48 (0%) 0
    Pruritus 8/50 (16%) 8 8/48 (16.7%) 11
    Rash 13/50 (26%) 21 7/48 (14.6%) 7
    Rash maculo-papular 3/50 (6%) 4 7/48 (14.6%) 12
    Vascular disorders
    Deep vein thrombosis 0/50 (0%) 0 3/48 (6.3%) 4
    Hypertension 0/50 (0%) 0 3/48 (6.3%) 3
    Hypotension 13/50 (26%) 17 3/48 (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/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone (800) 545-5979
    Email www.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