Cypress 1: Study of Pegilodecakin (LY3500518) With Pembrolizumab Compared to Pembrolizumab Alone First-line Tx in Participants With Metastatic Non-Small Cell Lung Cancer
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
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:
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
- 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
- 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.
- 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.
- 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.
- 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
Inclusion Criteria:
-
Participants must have histologically or cytologically confirmed WT NSCLC that is stage IV / metastatic or recurrent
-
Participants with tumor tissue high expression of PD-L1 as defined by Tumor Proportion Score (TPS) ≥ 50%
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Participants with measurable disease by spiral CT or MRI per RECIST v.1.1 criteria.
-
Participants that have completed prior radiotherapy or radiosurgery at least 2 weeks prior to randomization.
-
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:
-
Participants with active central nervous system (CNS) metastases or carcinomatous meningitis
-
Participants with any serious or uncontrolled medical disorder or active infection with the hepatitis virus or the human immunodeficiency virus (HIV)
-
Participants with Grade 1 (NCI-CTCAE v.4.03) toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue prior to randomization
-
Participants that have received pembrolizumab
-
Participants with a history of severe hypersensitivity reactions to monoclonal antibodies
-
Pregnant or lactating women
-
Participants receiving any investigational agent within 28 days of first administration of trial treatment
-
Participants that have received therapy with anti-tumor vaccines or other immunostimulatory antitumor agents
-
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.- 17160
- J1L-AM-JZGC
- AM0010-201
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
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. |
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. |
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. |
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. |
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
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 |
www.ClinicalTrials.gov@lilly.com |
- 17160
- J1L-AM-JZGC
- AM0010-201