A Study of Pemetrexed and Carboplatin/Cisplatin or Gemcitabine and Carboplatin/Cisplatin With or Without IMC-1121B in Participants Previously Untreated With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC)

An Open-label, Multicenter, Randomized, Phase 2 Study of a Recombinant Human Anti-VEGFR-2 Monoclonal Antibody, IMC-1121B in Combination With Platinum-based Chemotherapy Versus Platinum-based Chemotherapy Alone as First-line Treatment of Patients With Recurrent or Advanced Non-small Cell Lung Cancer (NSCLC)

The purpose of this study is to determine if participants with Stage IV NSCLC have a better outcome when treated with IMC-1121B in combination with pemetrexed + carboplatin/cisplatin or gemcitabine + carboplatin/cisplatin than when treated with pemetrexed + carboplatin/cisplatin or gemcitabine + carboplatin/cisplatin alone.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Biological: IMC-1121B (ramucirumab); Drug: Pemetrexed; Drug: Carboplatin (AUC 6); Drug: Cisplatin; Drug: Gemcitabine; Drug: Carboplatin (AUC 5)

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
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  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
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• Germany
  • Berlin, Germany, 14165
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  • Erlangen, Germany, 91054
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  • Großhansdorf, Germany, 22927
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  • Hemer, Germany, 58675
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  • Karlsruhe, Germany, 76137
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  • Regensburg, Germany, 93053
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  • Ulm, Germany, 89081
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• Poland
  • Gdansk, Poland, 80-952
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  • Olsztyn, Poland, 10-357
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  • Warsaw, Poland, 02-781
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• United Kingdom
  • Gwynedo
    • Bangor, Gwynedo, United Kingdom, LL57 2PW
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  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
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• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
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    • Tucson, Arizona, United States, 85704
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  • California
    • Corona, California, United States, 92879
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    • Fountain Valley, California, United States, 92708
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    • Riverside, California, United States, 92501
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  • Colorado
    • Aurora, Colorado, United States, 80045
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  • Florida
    • Fort Myers, Florida, United States, 33916
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    • Miami, Florida, United States, 33176
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  • Illinois
    • Chicago, Illinois, United States, 60612
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    • Peoria, Illinois, United States, 61615
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  • Kentucky
    • Louisville, Kentucky, United States, 40202
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  • Louisiana
    • Alexandria, Louisiana, United States, 71301
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  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
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  • Missouri
    • Columbia, Missouri, United States, 65201
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  • Nebraska
    • Lincoln, Nebraska, United States, 68506
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  • New Jersey
    • Neptune, New Jersey, United States, 07754
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  • New York
    • Bronx, New York, United States, 10467
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    • Latham, New York, United States, 12110
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  • Pennsylvania
    • Langhorne, Pennsylvania, United States, 19047
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • South Carolina
    • Hilton Head Island, South Carolina, United States, 29926
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Texas
    • Bedford, Texas, United States, 76022
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Dallas, Texas, United States, 75231
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    • El Paso, Texas, United States, 79915
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    • Fort Worth, Texas, United States, 76104
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    • Kerrville, Texas, United States, 78028
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    • Longview, Texas, United States, 75601
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    • McAllen, Texas, United States, 78503
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    • Midland, Texas, United States, 79701
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    • Paris, Texas, United States, 75460
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • San Antonio, Texas, United States, 78229
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    • The Woodlands, Texas, United States, 77380
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    • Tyler, Texas, United States, 75702
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Waco, Texas, United States, 76712
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Virginia
    • Christiansburg, Virginia, United States, 24073
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Fairfax, Virginia, United States, 22031
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Washington
    • Seattle, Washington, United States, 98133
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Spokane Valley, Washington, United States, 99216
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

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:

• Confirmed NSCLC
• Stage IV disease at the time of study entry
• Measurable disease at the time of study entry
• Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (except alopecia)
• Adequate hematologic function, hepatic function, renal function and coagulation function
• If sexually active, must be post-menopausal, surgically sterile, or using effective contraception; and agrees to use adequate contraception during the study period and for up to 6 months after the last dose of study medication
• Female participants of childbearing potential must have a negative serum pregnancy test

Exclusion Criteria:

• Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
• Tumor wholly or partially contains small cell lung cancer
• Untreated central nervous system (CNS) metastases, eligible if they are clinically stable with regard to neurologic function, off all steroids after cranial irradiation at least 2 weeks prior or after surgical resection performed at least 4 weeks prior to randomization
• Concurrent active malignancy other than adequately treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years
• Received prior therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR)
• Receiving concurrent treatment with other anticancer therapy
• Has received previous chemotherapy for Stage IV NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 6 months prior to randomization)
• Has radiologically documented evidence of major blood vessel invasion or encasement by cancer
• Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions)
• Ongoing or active infection
• History of significant neurological or psychiatric disorders
• Experienced clinically relevant coronary artery disease, myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, or symptomatic poorly controlled arrhythmia
• Poorly-controlled hypertension
• Experienced any serious Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry
• Receiving chronic daily treatment with aspirin (> 325 mg/day) or other known inhibitors of platelet function
• Serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
• Major surgery within 28 days prior the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to randomization
• Elective or a planned major surgery
• Pregnant or lactating
• Any other serious uncontrolled medical disorders or psychological conditions
• Allergy / history of hypersensitivity reaction to any of the treatment components
• History of drug abuse

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMC-1121B + Pemetrexed + Carboplatin (AUC 6) or Cisplatin; IMC-1121B + Pemetrexed + Carboplatin [Area Under the Concentration Time Curve 6 (AUC 6)] or Cisplatin	Biological: IMC-1121B (ramucirumab); 10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1; Other Names: LY3009806; IMC-1121B; ramucirumab; Drug: Pemetrexed; 500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle; Drug: Carboplatin (AUC 6); Day 1 of every 21-day cycle; Drug: Cisplatin; 75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle
Active Comparator: Pemetrexed + Carboplatin (AUC 6) or Cisplatin	Drug: Pemetrexed; 500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle; Drug: Carboplatin (AUC 6); Day 1 of every 21-day cycle; Drug: Cisplatin; 75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle
Experimental: IMC-1121B + Gemcitabine + Carboplatin (AUC 5) or Cisplatin; IMC-1121B + Gemcitabine + Carboplatin [Area Under the Concentration Time Curve 5 (AUC 5)] or Cisplatin	Biological: IMC-1121B (ramucirumab); 10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1; Other Names: LY3009806; IMC-1121B; ramucirumab; Drug: Cisplatin; 75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle; Drug: Gemcitabine; 1000 mg/m² on Days 1 and 8 of every 21-day cycle; Drug: Carboplatin (AUC 5); Day 1 of every 21-day cycle
Active Comparator: Gemcitabine + Carboplatin (AUC 5) or Cisplatin	Drug: Cisplatin; 75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle; Drug: Gemcitabine; 1000 mg/m² on Days 1 and 8 of every 21-day cycle; Drug: Carboplatin (AUC 5); Day 1 of every 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was the time from randomization to the first objective progression as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1) or death from any cause, whichever occurred first. Progressive disease (PD) was defined as ≥20% increase in sum of diameter (SOD) of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 millimeters (mm); appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants alive and without disease progression were censored at the time of the last objective tumor assessment. Participants who did not progress and were lost to follow-up were censored at their last radiographic assessment. If no baseline or post baseline radiologic assessments were available, participants were censored at date of randomization.	Randomization to PD or death (up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]	Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100.	Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)
Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of death from any cause. If the participant was alive at the end of the follow-up period or was lost to follow-up, OS was censored on the last date the participant was known to be alive.	Randomization to the date of death from any cause (up to 31.3 months)
Duration of Response (DOR)	DOR was measured from the time criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death. Response was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker level of non-target lesions. PR was defined as ≥30% decrease SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who did not relapse were censored at the day of their last objective tumor assessment.	Time of first response (CR or PR) until PD or death (up to 24 months)
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died	Data presented are the number of participants with at least 1 treatment-emergent adverse event (TEAE) and treatment-emergent serious adverse event (SAE), as well as, the number of participants who died during the study. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). A summary of SAEs and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.	Day 1, Cycle 1 (3-week cycles) Up to 3 Years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)]	DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)*100.	Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)
Change in Tumor Size (CTS)	CTS was defined as the log ratio of tumor size at 6 weeks to tumor size at baseline. CTS at 6 weeks=Log (Sum of Target Lesion Measurements at 6 Weeks)-Log (Sum of Target Lesion Measurements at Baseline).	Baseline, 6 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Doebele RC, Spigel D, Tehfe M, Thomas S, Reck M, Verma S, Eakle J, Bustin F, Goldschmidt J Jr, Cao D, Alexandris E, Yurasov S, Camidge DR, Bonomi P. Phase 2, randomized, open-label study of ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in patients with nonsquamous, advanced/metastatic non-small cell lung cancer. Cancer. 2015 Mar 15;121(6):883-92. doi: 10.1002/cncr.29132. Epub 2014 Nov 6.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: July 8, 2010
• First Submitted That Met QC Criteria: July 9, 2010
• First Posted (Estimate): July 12, 2010

Study Record Updates

• Last Update Posted (Actual): September 13, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Lung cancer; Non-small Cell Lung Cancer; Lung neoplasms; pemetrexed; squamous; nonsquamous
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Folic Acid Antagonists; Gemcitabine; Carboplatin; Ramucirumab; Antibodies, Monoclonal; Pemetrexed
• Other Study ID Numbers: 13916; I4T-IE-JVBL (Other Identifier: Eli Lilly and Company); CP12-0917 (Other Identifier: ImClone Systems); 2009-016784-11 (EudraCT Number)

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 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