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A Phase 1 Study of Pegilodecakin (LY3500518) in Participants With Advanced Solid Tumors (IVY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02009449
Recruitment Status : Active, not recruiting
First Posted : December 12, 2013
Last Update Posted : September 5, 2021
Sponsor:
Collaborator:
ARMO BioSciences
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE December 2, 2013
First Posted Date  ICMJE December 12, 2013
Last Update Posted Date September 5, 2021
Actual Study Start Date  ICMJE November 15, 2013
Actual Primary Completion Date February 19, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2014)
  • Safety and tolerability as measured by incidence of adverse events [ Time Frame: up to 12 months ]
  • Pharmacokinetic (PK) parameters [ Time Frame: up to 12 months ]
    PK parameters including the serum trough concentration (Minimal Drug Concentration (Cmin)), the maximal drug concentration (Cmax), area under the curve of serum concentration over time (Area Under the Curve/ AUC), and half-life (t½).
Original Primary Outcome Measures  ICMJE
 (submitted: December 9, 2013)
  • Safety and tolerability as measured by incidence of adverse events [ Time Frame: approximately 4 months ]
  • Pharmacokinetic (PK) parameters [ Time Frame: Approximately 4 months ]
    PK parameters including the serum trough concentration (Minimal Drug Concentration (Cmin)), the maximal drug concentration (Cmax), area under the curve of serum concentration over time (Area Under the Curve/ AUC), and half-life (t½).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
  • Change in tumor burden measured by volumetric Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) according to immune-related response criteria (irRC) [ Time Frame: up to 12 months ]
  • Progression in bone by bone scintigraphy according to Prostate Cancer Working Group 2 (PCWG2) for participants with metastatic castration resistant prostate cancer (CRPC) [ Time Frame: approximatley 4 months ]
  • Anti-Pegilodecakin antibody formation [ Time Frame: up to 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2013)
  • Change in tumor burden measured by volumetric Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) according to immune-related response criteria (irRC) [ Time Frame: approxinatetly 4 months ]
  • Progression in bone by bone scintigraphy according to Prostate Cancer Working Group 2 (PCWG2) for patients with metastatic castration resistant prostate cancer (CRPC) [ Time Frame: approximatley 4 months ]
  • Anti-AM0010 antibody formation [ Time Frame: approximately 4 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of Pegilodecakin (LY3500518) in Participants With Advanced Solid Tumors
Official Title  ICMJE A Phase 1, Open-Label Dose Escalation First-in-Human Study to Evaluate the Tolerability, Safety, Maximum Tolerated Dose, Preliminary Clinical Activity and Pharmacokinetics of AM0010 in Patients With Advanced Solid Tumors
Brief Summary This is a first-in-human, open-label, dose escalation study to evaluate the safety and tolerability of pegilodecakin in participants with advanced solid tumors, dosed daily subcutaneously as a monotherapy or in combination with chemotherapy or immunotherapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Melanoma
  • Prostate Cancer
  • Ovarian Cancer
  • Renal Cell Carcinoma
  • Colorectal Carcinoma
  • Pancreatic Carcinoma
  • Non-small Cell Lung Carcinoma
  • Solid Tumors
  • Breast Cancer
Intervention  ICMJE
  • Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
    • LY3500518
    • AM0010
    • PEGylated recombinant human Interleukin-10
    • PEG-rHuIL-10
  • Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
    Day 1 of every 21 day cycle
    Other Name: Taxol or taxotere and paraplatin or platinol
  • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
    Intravenous administration on Day 1 and 2 of every 14 day cycle
    Other Name: Eloxatin®/Leucovorin/5-FU
  • Drug: gemcitabine/nab-paclitaxel
    Intravenous administration of the gemcitabine/nab-paclitaxel regimen on Day 1, 8 and 15 of each 28 day treatment cycle.
    Other Name: Gemzar/Abraxane ABI-007
  • Drug: Capecitabine
    Capecitabine will be administered orally twice daily for 14 days out of every 21 days.
    Other Name: Xeloda
  • Drug: Pazopanib
    Pazopanib will be administered orally daily continuously
    Other Name: GW786034
  • Drug: Pembrolizumab
    Pembrolizumab will be administered intravenously on Day 1 of every 21 day cycle.
    Other Name: Keytruda, MK-3475
  • Drug: Paclitaxel

    Paclitaxel will be administered intravenously on Days 1, 8, 15 of each cycle (28 days= 1 cycle)

    • Paclitaxel 80 mg/ m2 IV

  • Drug: nivolumab
    Nivolumab on Day 1 of each cycle (14 days = 1 cycle)
    Other Name: Keytruda
  • Drug: Gemcitabine/carboplatin
    gemcitabine and carboplatin on Days 1, 8 of each cycle (21 days = 1 cycle)
    Other Name: gemzar/paraplatin
Study Arms  ICMJE
  • Experimental: Part A: Dose Escalation Cohort 1
    Pegilodecakin (1 ug/kg) - Daily subcutaneous (SC) injections of pegilodecakin for up to 22 months
    Intervention: Drug: Pegilodecakin
  • Experimental: Part A: Dose Escalation Cohort 2
    Pegilodecakin (2.5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
    Intervention: Drug: Pegilodecakin
  • Experimental: Part A: Dose Escalation Cohort 3
    Pegilodecakin (5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
    Intervention: Drug: Pegilodecakin
  • Experimental: Part A: Dose Escalation Cohort 4
    Pegilodecakin (10 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
    Intervention: Drug: Pegilodecakin
  • Experimental: Part A: Dose Escalation Cohort 5
    Pegilodecakin (20 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
    Intervention: Drug: Pegilodecakin
  • Experimental: Part A: Dose Escalation Cohort 6
    Pegilodecakin (40 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
    Intervention: Drug: Pegilodecakin
  • Experimental: Part A: Dose Expansion Cohort 1
    at least 15 RCC participants will be dosed with pegilodecakin for up to 22 months
    Intervention: Drug: Pegilodecakin
  • Experimental: Part B: Dose Escalation Cohort 1

    Pegilodecakin (2.5 ug/kg) daily subcutaneous injections with Platinum / Taxane combination Every 21 days, (21 days = 1 cycle) for 5 cycles.

    Day 1

    • Paclitaxel 200/175 mg/m2 IV, or
    • Docetaxel 75/65 mg/m2 IV And
    • Carboplatin AUC 6/5/4 (max. 6x 150mg) IV or
    • Cisplatin 75mg/m2 IV
    Interventions:
    • Drug: Pegilodecakin
    • Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
  • Experimental: Part B: Dose Escalation Cohort 2

    Pegilodecakin (5 ug/kg) daily subcutaneous injections with Platinum / Taxane combination Every 21 days, (21 days = 1 cycle) for 5 cycles.

    Day 1

    • Paclitaxel 200/175 mg/m2 IV, or
    • Docetaxel 75/65 mg/m2 IV And
    • Carboplatin AUC 6/5/4 (max. 6x 150mg) IV or
    • Cisplatin 75mg/m2 IV
    Interventions:
    • Drug: Pegilodecakin
    • Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
  • Experimental: Part B: Dose Escalation Cohort 3

    Pegilodecakin (10 ug/kg) daily subcutaneous injections with Platinum / Taxane combination Every 21 days, (21 days = 1 cycle) for 5 cycles.

    Day 1

    • Paclitaxel 200/175 mg/m2 IV, or
    • Docetaxel 75/65 mg/m2 IV And
    • Carboplatin AUC 6/5/4 (max. 6x 150mg) IV or
    • Cisplatin 75mg/m2 IV
    Interventions:
    • Drug: Pegilodecakin
    • Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
  • Experimental: Part B: Dose Expansion Cohort

    Daily SC injection with pegilodecakin with Platinum / Taxane combination Every 21 days, (21 days = 1 cycle) for 5 cycles.

    Day 1

    • Paclitaxel 200/175 mg/m2 IV, or
    • Docetaxel 75/65 mg/m2 IV And
    • Carboplatin AUC 6/5/4 (max. 6x 150mg) IV or
    • Cisplatin 75mg/m2 IV
    Interventions:
    • Drug: Pegilodecakin
    • Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
  • Experimental: Part C: Dose Escalation Cohort 1

    Pegilodecakin (2.5 ug/kg) daily subcutaneous injections with FOLFOX4 every 14 days FOLFOX4; (14 days = 1 cycle) ;

    Day 1

    • Oxaliplatin 85 mg/m2 IV over 2 hours
    • Leucovorin 200 mg/m2 IV over 2 hours followed by
    • 5-FU 400 mg/m2 IV bolus and
    • 5-FU 600 mg/m2/day IV over 22 hours
    • Leucovorin 200 mg/m2 IV over 2 hours on Day 2 followed by
    • 5-FU 400 mg/m2 IV bolus and
    • 5-FU 600 mg/m2/day IV over 22 hours
    Interventions:
    • Drug: Pegilodecakin
    • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
  • Experimental: Part C: Dose Escalation Cohort 2

    Pegilodecakin (5 ug/kg) daily subcutaneous injections with FOLFOX4 every 14 days FOLFOX4; (14 days = 1 cycle) ;

    Day 1

    • Oxaliplatin 85 mg/m2 IV over 2 hours
    • Leucovorin 200 mg/m2 IV over 2 hours followed by
    • 5-FU 400 mg/m2 IV bolus and
    • 5-FU 600 mg/m2/day IV over 22 hours
    • Leucovorin 200 mg/m2 IV over 2 hours on Day 2 followed by
    • 5-FU 400 mg/m2 IV bolus and
    • 5-FU 600 mg/m2/day IV over 22 hours
    Interventions:
    • Drug: Pegilodecakin
    • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
  • Experimental: Part C: Dose Escalation Cohort 3

    Pegilodecakin (10 ug/kg) daily subcutaneous injections with FOLFOX4 every 14 days FOLFOX4; (14 days = 1 cycle) ;

    Day 1

    • Oxaliplatin 85 mg/m2 IV over 2 hours
    • Leucovorin 200 mg/m2 IV over 2 hours followed by
    • 5-FU 400 mg/m2 IV bolus and
    • 5-FU 600 mg/m2/day IV over 22 hours
    • Leucovorin 200 mg/m2 IV over 2 hours on Day 2 followed by
    • 5-FU 400 mg/m2 IV bolus and
    • 5-FU 600 mg/m2/day IV over 22 hours
    Interventions:
    • Drug: Pegilodecakin
    • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
  • Experimental: Part C: Dose Expansion Cohort 1

    Daily SC injection with pegilodecakin with FOLFOX4 Every 14 days FOLFOX4; (14 days = 1 cycle) ;

    Day 1

    • Oxaliplatin 85 mg/m2 IV over 2 hours
    • Leucovorin 200 mg/m2 IV over 2 hours followed by
    • 5-FU 400 mg/m2 IV bolus and
    • 5-FU 600 mg/m2/day IV over 22 hours
    • Leucovorin 200 mg/m2 IV over 2 hours on Day 2 followed by
    • 5-FU 400 mg/m2 IV bolus and
    • 5-FU 600 mg/m2/day IV over 22 hours
    Interventions:
    • Drug: Pegilodecakin
    • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
  • Experimental: Part D: Dose Escalation Cohort 1

    Pegilodecakin (5 ug/kg) daily subcutaneous injections with Gemcitabine and nab-paclitaxel on Days 1, 8, 15 of each cycle (28 days = 1 cycle).

    Nab-paclitaxel 125 mg/m2 IV over 30 minutes followed by

    • Gemcitabine 1000 mg/m2 IV.

    Interventions:
    • Drug: Pegilodecakin
    • Drug: gemcitabine/nab-paclitaxel
  • Experimental: Part E: Dose Escalation Cohort 1

    Pegilodecakin (10 ug/kg) daily subcutaneous injections with capecitabine BID daily for 14 days of each cycle (21 days= 1 cycle).

    • Capecitabine 1000 mg/m2 po BID

    Interventions:
    • Drug: Pegilodecakin
    • Drug: Capecitabine
  • Experimental: Part F: Dose Escalation Cohort 1

    Pegilodecakin (10 ug/kg) daily subcutaneous injections with paclitaxel on Days 1, 8, 15 of each cycle (28 days= 1 cycle)

    • Paclitaxel 80 mg/ m2 IV

    Interventions:
    • Drug: Pegilodecakin
    • Drug: Paclitaxel
  • Experimental: Part G: Dose Escalation Cohort 1

    Pegilodecakin (10 ug/kg) daily subcutaneous injections with pazopanib orally given daily for 14 days of each cycle (21 days= 1 cycle)

    • Pazopanib 800 mg po QD

    Interventions:
    • Drug: Pegilodecakin
    • Drug: Pazopanib
  • Experimental: Part H: Dose Escalation Cohort 1

    Pegilodecakin (10 ug/kg) daily subcutaneous injections with pembrolizumab on Day 1 of each cycle (21 days= 1 cycle).

    • Pembrolizumab 2 mg/kg IV over 30 min

    Interventions:
    • Drug: Pegilodecakin
    • Drug: Pembrolizumab
  • Experimental: Part I: Dose Escalation Cohort 1

    Pegilodecakin (20 ug/kg) daily subcutaneous injections with nivolumab on Day 1 of each cycle (14 days= 1 cycle).

    • Nivolumab 3 mg/kg IV over 60 min

    Intervention: Drug: nivolumab
  • Experimental: Part H: Dose Escalation Cohort 2

    Pegilodecakin (20 ug/kg) daily subcutaneous injections with pembrolizumab on Day 1 of each cycle (21 days= 1 cycle).

    • Pembrolizumab 2 mg/kg IV over 30 min

    Intervention: Drug: Pembrolizumab
  • Experimental: Part H: Dose Escalation Cohort 3

    Pegilodecakin (40 ug/kg) daily subcutaneous injections with pembrolizumab on Day 1 of each cycle (21 days= 1 cycle).

    • Pembrolizumab 2 mg/kg IV over 30 min

    Intervention: Drug: Pembrolizumab
  • Experimental: Part J: Dose Escalation Cohort 1
    Pegilodecakin (10 ug/kg) daily subcutaneous injections with gemcitabine and carbolplatin on Days 1,8 of each cycle (21 days=1 cycle) until disease progression gemcitabine 1000mg/m2 IV over 30 minutes followed by carboplatin AUC2 over 60 minutes
    Intervention: Drug: Gemcitabine/carboplatin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 15, 2017)
350
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2013)
45
Estimated Study Completion Date  ICMJE November 15, 2022
Actual Primary Completion Date February 19, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Part A Escalation Cohorts:

o Histologically or cytologically confirmed advanced malignant solid tumor, limited to melanoma, castrate resistant prostate cancer (CRPC), ovarian cancer (OVCA), renal cell carcinoma, colorectal carcinoma (CRC), pancreatic carcinoma or non-small cell lung carcinoma (NSCLC) that is refractory to, intolerant of, for which no standard of therapy is available or where the participant refuses existing therapies

Part A Expansion Cohorts, Part B and C Escalation and Expansion Cohorts:

  • Tumors with all histological diagnosis or tissue origin may be enrolled
  • Participants must have failed prior standard curative chemotherapy for their disease, refuse existing therapies OR the proposed chemotherapy regimen to which pegilodecakin is added represents an acceptable standard treatment for their disease.

    • Measurable or evaluable disease according to irRC or bone metastatic disease evaluable by Prostate Cancer Working Group 2 criteria (PCWG2) for castration-resistant prostate cancer (CRPC)
    • At least 18 years of age
    • Performance Status of 0 or 1
    • Adequate organ function

Exclusion Criteria:

  • Hematologic malignancies
  • Pregnant or lactating
  • Present or history of neurological disorders such as Multiple Sclerosis and Guillain Barre or inflammatory central nervous system/peripheral nervous system (CNS/PNS) disorders
  • Myocardial infarction within the last 6 months
  • Unstable angina, or unstable cardiac arrhythmia requiring medication
  • Surgery within the last 28 days
  • Systemic fungal, bacterial, viral, or other infection
  • History of bleeding diathesis within the last 6 months
  • Positive for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02009449
Other Study ID Numbers  ICMJE 17159
J1L-AM-JZGA ( Other Identifier: Eli Lilly and Company )
AM0010-001 ( Other Identifier: ARMO BioSciences )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE ARMO BioSciences
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP