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

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%)

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.

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Biological: Pegilodecakin; Drug: Pembrolizumab

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 Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • CCI - Clearview Cancer Institute
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Arizona Oncology Associates, P.C.
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Fullerton, California, United States, 92835
      • St. Joseph Heritage Medical Group
    • Los Angeles, California, United States, 90017
      • Glendale Adventist Medical Center
    • Redlands, California, United States, 92373
      • Redlands Community Hospital
    • Santa Rosa, California, United States, 95403
      • Redwood Regional Oncology Center
    • Whittier, California, United States, 90602
      • The Oncology Institute of Hope and Innovation
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente Oncology Clinic
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Center
  • Connecticut
    • West Haven, Connecticut, United States, 06516-2770
      • Veterans Affairs Connecticut Healthcare System
  • Delaware
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematolgy Consultants, PA
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute Ctr for Hem-Onc
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Cancer Institute
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Cancer Center
    • Tallahassee, Florida, United States, 32308
      • SCRI- Florida Cancer Specialists
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists East
  • Georgia
    • Athens, Georgia, United States, 30607
      • Northeast Georgia Cancer Care, LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Pacific Diabetes & Endocrine Center
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • AMITA Health Cancer Institute & Outpatient Center
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research Inc
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Goshen Health System
  • Iowa
    • Iowa City, Iowa, United States, 52242-1009
      • University of Iowa
    • Waterloo, Iowa, United States, 50702
      • Covenant Clinic
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Medical Group
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Medstar Research Institute
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A.
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital Detroit
    • Lansing, Michigan, United States, 48912
      • Sparrow Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Hospital
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology/Hematology PA
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • St John's Mercy Medical Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Nebraska Hematology-Oncology
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Medical Center
    • Westwood, New Jersey, United States, 07675
      • The Valley Hospital - Luckow Pavilion
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance, Inc.
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • DJL Clinical Research, PLLC
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Cincinnati, Ohio, United States, 45219
      • Christ Hospital
    • Toledo, Ohio, United States, 43623
      • The Toledo Clinic
    • Toledo, Ohio, United States, 43614-2598
      • University of Toledo Medical Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oncology Associates of Oregon
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology Hematology Associates
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute SCRI
  • Texas
    • Abilene, Texas, United States, 79606
      • Texas Cancer Center (Abilene)
    • Beaumont, Texas, United States, 77702
      • Mamie McFaddin Ward Cancer Center
    • Dallas, Texas, United States, 75231
      • Texas Oncology - Dallas Presbyterian Hospital
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77024
      • Texas Oncology-Memorial City
    • Houston, Texas, United States, 77090
      • Millennium Oncology
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Center
    • Midland, Texas, United States, 79701
      • Texas Oncology - Midland Allison Cancer Center
    • Sherman, Texas, United States, 75090-0504
      • Texas Oncology-Sherman
    • The Woodlands, Texas, United States, 77380
      • US Oncology
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
    • Webster, Texas, United States, 77598-4219
      • Texas Oncology-Deke Slayton Cancer Center
    • Wichita Falls, Texas, United States, 76310
      • Texas Oncology-Wichital Falls Texoma Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Fairfax Northern Virginia Hematology Oncology, PC
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia Inc
    • Winchester, Virginia, United States, 22601
      • Shenandoah Oncology, P.C.
  • Washington
    • Tacoma, Washington, United States, 98002
      • MultiCare Regional Cancer Center - Auburn
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • The Richland Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved an Objective Response Rate (ORR)	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.	From Date of Randomization to Progressive Disease, Death from Any cause (Up to 24 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	From Date of Randomization to Death Due to Any Cause (Up to 24 Months)
Progression Free Survival (PFS)	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.	From Date of Randomization to Progressive Disease (PD) or Death Due to Any Cause (Up to 24 Months)
Percentage of Participants Who Achieved a Disease Control Rate (DCR)	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.	From Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 24 Months)
Duration of Response (DOR)	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.	From Date of Response to Death Due to Any Cause (Up to 24 Months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: ARMO BioSciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2018
• Primary Completion (Actual): December 6, 2019
• Study Completion (Actual): March 5, 2020

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: December 21, 2017
• First Posted (Actual): December 26, 2017

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: 17160; J1L-AM-JZGC (Other Identifier: Eli Lilly and Company); AM0010-201 (Other Identifier: ARMO BioSciences)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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 European Union (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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No