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

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

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.

Study Overview

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

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%).

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Arizona Oncology Associates, P.C.
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Los Angeles, California, United States, 90017
      • Glendale Adventist Medical Center
    • Santa Rosa, California, United States, 95403
      • Redwood Regional Oncology Center
    • Whittier, California, United States, 90602
      • The Oncology Institute of Hope and Innovation
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
  • Iowa
    • Waterloo, Iowa, United States, 50702
      • Covenant Clinic
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MedStar Health Research Institute
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A.
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Sparrow Health System
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic
  • New Jersey
    • Westwood, New Jersey, United States, 07675
      • The Valley Hospital - Luckow Pavilion
  • New York
    • Johnson City, New York, United States, 13790
      • Broome Oncology LLC
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New Hyde Park, New York, United States, 11042
      • Clinical Research Alliance, Inc.
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Cincinnati, Ohio, United States, 45219
      • Christ Hospital
    • Toledo, Ohio, United States, 43614-2598
      • University of Toledo Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates
  • Texas
    • 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
    • The Woodlands, Texas, United States, 77380
      • US Oncology
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • 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
  • Washington
    • Tacoma, Washington, United States, 98002
      • MultiCare Regional Cancer Center - Auburn

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pegilodecakin+Nivolumab; 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).	Biological: Pegilodecakin; Pegilodecakin plus Nivolumab; Other Names: LY3500518; AM0010; Drug: Nivolumab; Nivolumab Alone
ACTIVE_COMPARATOR: Nivolumab; 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).	Drug: Nivolumab; Nivolumab Alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Date of Randomization to Progressive Disease, Death from Any cause (Up to 6 months after the last participant randomized)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized)
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.	From Date of Randomization to Progressive Disease or Death Due to Any Cause (Up to 6 months after the last participant randomized)
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.	From Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months after the last participant randomization)
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.	From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized)

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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 22, 2018
• Primary Completion (ACTUAL): August 28, 2019
• Study Completion (ACTUAL): March 3, 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): September 11, 2020
• Last Update Submitted That Met QC Criteria: August 22, 2020
• Last Verified: June 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: 17161; J1L-AM-JZGD (OTHER: Eli Lilly and Company); AM0010-202 (OTHER: ARMO BioSciences)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 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