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Study of Pegilodecakin (LY3500518) With Nivolumab Compared to Nivolumab Alone Second-line Tx in Participants With Metastatic Non-Small Cell Lung Cancer (Cypress 2)

Primary Purpose

Non Small Cell Lung Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pegilodecakin
Nivolumab
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Participants must have histologically or cytologically confirmed Wild Type NSCLC that is stage IV / metastatic or recurrent
  2. Participants must have received at least one prior systemic therapy that was not an anti-PD-1, anti-PD-L1 and/or anti-CTLA-4 treatment for the advanced stage of the disease
  3. Participants with tumor tissue low expression of PD-L1 as defined by Tumor Proportion Score (TPS) 0% - 49%
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Participants with measurable disease by spiral computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumor (RECIST) v.1.1 criteria
  6. Participants that have completed prior radiotherapy or radiosurgery at least 2 weeks prior to randomization

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 nivolumab
  5. Participants that have received therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents
  6. Participants with a history of severe hypersensitivity reactions to monoclonal antibodies
  7. 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
  8. Participants receiving any investigational agent within 28 days of first administration of trial treatment
  9. Pregnant or lactating women

Sites / Locations

  • Arizona Oncology Associates, P.C.
  • Beverly Hills Cancer Center
  • Glendale Adventist Medical Center
  • Redwood Regional Oncology Center
  • The Oncology Institute of Hope and Innovation
  • Rocky Mountain Cancer Center
  • John B. Amos Cancer Center
  • Covenant Clinic
  • Baptist Health Medical Group
  • MedStar Health Research Institute
  • Maryland Oncology Hematology, P.A.
  • Frederick Memorial Hospital
  • Sparrow Health System
  • Hattiesburg Clinic
  • The Valley Hospital - Luckow Pavilion
  • Broome Oncology LLC
  • Winthrop University Hospital
  • Clinical Research Alliance, Inc.
  • Stony Brook University Medical Center
  • Gabrail Cancer Center
  • Christ Hospital
  • University of Toledo Medical Center
  • Charleston Hematology Oncology Associates
  • Mamie McFaddin Ward Cancer Center
  • Texas Oncology - Dallas Presbyterian Hospital
  • Texas Oncology-Baylor Charles A. Sammons Cancer Center
  • Texas Oncology-Memorial City
  • Millennium Oncology
  • Joe Arrington Cancer Center
  • Texas Oncology - Midland Allison Cancer Center
  • US Oncology
  • Texas Oncology - Tyler
  • Fairfax Northern Virginia Hematology Oncology, PC
  • Oncology and Hematology Associates of Southwest Virginia Inc
  • MultiCare Regional Cancer Center - Auburn

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pegilodecakin+Nivolumab

Nivolumab

Arm Description

Participants received Pegilodecakin subcutaneously 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. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every 2 weeks (Q2W), or 480 mg every 4 weeks (Q4W).

Participants received Nivolumab on day 1 of each 14- or 28- day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every two weeks (Q2W), or 480 mg every 4 weeks (Q4W).

Outcomes

Primary Outcome Measures

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

Secondary Outcome Measures

Overall Survival (OS)
OS is defined as the time from first day of therapy to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up, OS was censored on the last date the participant was known to be alive.
Progression Free Survival (PFS)
PFS is defined as the time from the day of randomization to the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria or death from any cause. Progressive Disease (PD) is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment.
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD)
Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Duration of Response
Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.

Full Information

First Posted
December 18, 2017
Last Updated
August 22, 2020
Sponsor
Eli Lilly and Company
Collaborators
ARMO BioSciences
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1. Study Identification

Unique Protocol Identification Number
NCT03382912
Brief Title
Study of Pegilodecakin (LY3500518) With Nivolumab Compared to Nivolumab Alone Second-line Tx in Participants With Metastatic Non-Small Cell Lung Cancer
Acronym
Cypress 2
Official Title
A Randomized Phase 2 Trial of AM0010 in Combination With Nivolumab vs. Nivolumab Alone as Second-Line Therapy in Subjects With Stage IV / Metastatic Wild Type Non-Small Cell Lung Cancer and Low Tumor Expression of PD-L1
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
The CYPRESS-2 trial was closed early after the planned final analysis because the risk benefit ratio is unfavorable.
Study Start Date
March 22, 2018 (Actual)
Primary Completion Date
August 28, 2019 (Actual)
Study Completion Date
March 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
Collaborators
ARMO BioSciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To compare the efficacy of pegilodecakin in combination with nivolumab versus nivolumab alone in participants with metastatic non-small cell lung cancer as measured by objective response rate.
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 nivolumab versus nivolumab alone in participants with stage IV / metastatic wild type non-small cell lung cancer and tumors with low tumor expression of PD-L1 (0-49%).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pegilodecakin+Nivolumab
Arm Type
Experimental
Arm Description
Participants received Pegilodecakin subcutaneously 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. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every 2 weeks (Q2W), or 480 mg every 4 weeks (Q4W).
Arm Title
Nivolumab
Arm Type
Active Comparator
Arm Description
Participants received Nivolumab on day 1 of each 14- or 28- day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every two weeks (Q2W), or 480 mg every 4 weeks (Q4W).
Intervention Type
Biological
Intervention Name(s)
Pegilodecakin
Other Intervention Name(s)
LY3500518, AM0010
Intervention Description
Pegilodecakin plus Nivolumab
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
Nivolumab Alone
Primary Outcome Measure Information:
Title
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Description
Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Time Frame
From Date of Randomization to Progressive Disease, Death from Any cause (Up to 6 months after the last participant randomized)
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS is defined as the time from first day of therapy to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up, OS was 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 6 months after the last participant randomized)
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from the day of randomization to the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria or death from any cause. Progressive Disease (PD) is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment.
Time Frame
From Date of Randomization to Progressive Disease or Death Due to Any Cause (Up to 6 months after the last participant randomized)
Title
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD)
Description
Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time Frame
From Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months after the last participant randomization)
Title
Duration of Response
Description
Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.
Time Frame
From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have histologically or cytologically confirmed Wild Type NSCLC that is stage IV / metastatic or recurrent Participants must have received at least one prior systemic therapy that was not an anti-PD-1, anti-PD-L1 and/or anti-CTLA-4 treatment for the advanced stage of the disease Participants with tumor tissue low expression of PD-L1 as defined by Tumor Proportion Score (TPS) 0% - 49% Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Participants with measurable disease by spiral computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumor (RECIST) v.1.1 criteria Participants that have completed prior radiotherapy or radiosurgery at least 2 weeks prior to randomization 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 nivolumab Participants that have received therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents Participants with a history of severe hypersensitivity reactions to monoclonal antibodies 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 Participants receiving any investigational agent within 28 days of first administration of trial treatment Pregnant or lactating women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology Associates, P.C.
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85284
Country
United States
Facility Name
Beverly Hills Cancer Center
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Glendale Adventist Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90017
Country
United States
Facility Name
Redwood Regional Oncology Center
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
Facility Name
The Oncology Institute of Hope and Innovation
City
Whittier
State/Province
California
ZIP/Postal Code
90602
Country
United States
Facility Name
Rocky Mountain Cancer Center
City
Lone Tree
State/Province
Colorado
ZIP/Postal Code
80124
Country
United States
Facility Name
John B. Amos Cancer Center
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
Covenant Clinic
City
Waterloo
State/Province
Iowa
ZIP/Postal Code
50702
Country
United States
Facility Name
Baptist Health Medical Group
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Facility Name
MedStar Health Research Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21237
Country
United States
Facility Name
Maryland Oncology Hematology, P.A.
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21044
Country
United States
Facility Name
Frederick Memorial Hospital
City
Frederick
State/Province
Maryland
ZIP/Postal Code
21701
Country
United States
Facility Name
Sparrow Health System
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48912
Country
United States
Facility Name
Hattiesburg Clinic
City
Hattiesburg
State/Province
Mississippi
ZIP/Postal Code
39401
Country
United States
Facility Name
The Valley Hospital - Luckow Pavilion
City
Westwood
State/Province
New Jersey
ZIP/Postal Code
07675
Country
United States
Facility Name
Broome Oncology LLC
City
Johnson City
State/Province
New York
ZIP/Postal Code
13790
Country
United States
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Clinical Research Alliance, Inc.
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Stony Brook University Medical Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
University of Toledo Medical Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614-2598
Country
United States
Facility Name
Charleston Hematology Oncology Associates
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29414
Country
United States
Facility Name
Mamie McFaddin Ward Cancer Center
City
Beaumont
State/Province
Texas
ZIP/Postal Code
77702
Country
United States
Facility Name
Texas Oncology - Dallas Presbyterian Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Texas Oncology-Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Texas Oncology-Memorial City
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
Millennium Oncology
City
Houston
State/Province
Texas
ZIP/Postal Code
77090
Country
United States
Facility Name
Joe Arrington Cancer Center
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
Texas Oncology - Midland Allison Cancer Center
City
Midland
State/Province
Texas
ZIP/Postal Code
79701
Country
United States
Facility Name
US Oncology
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77380
Country
United States
Facility Name
Texas Oncology - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Fairfax Northern Virginia Hematology Oncology, PC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Oncology and Hematology Associates of Southwest Virginia Inc
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24014
Country
United States
Facility Name
MultiCare Regional Cancer Center - Auburn
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98002
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Yes Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
http://www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
33166722
Citation
Spigel D, Jotte R, Nemunaitis J, Shum M, Schneider J, Goldschmidt J, Eisenstein J, Berz D, Seneviratne L, Socoteanu M, Bhanderi V, Konduri K, Xia M, Wang H, Hozak RR, Gueorguieva I, Ferry D, Gandhi L, Chao BH, Rybkin I. Randomized Phase 2 Studies of Checkpoint Inhibitors Alone or in Combination With Pegilodecakin in Patients With Metastatic NSCLC (CYPRESS 1 and CYPRESS 2). J Thorac Oncol. 2021 Feb;16(2):327-333. doi: 10.1016/j.jtho.2020.10.001. Epub 2020 Nov 6.
Results Reference
derived
PubMed Identifier
32808556
Citation
Albrethsen M, Creeden J, Morand S, DeBiase J, Berry B, Stanbery L, Edelman G, Nemunaitis J. Relationship of hypothyroidism and immune response to pegylated IL-10/nivolumab. Immunotherapy. 2020 Oct;12(14):1041-1046. doi: 10.2217/imt-2020-0016. Epub 2020 Aug 18.
Results Reference
derived

Learn more about this trial

Study of Pegilodecakin (LY3500518) With Nivolumab Compared to Nivolumab Alone Second-line Tx in Participants With Metastatic Non-Small Cell Lung Cancer

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