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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02009449
Collaborator
ARMO BioSciences (Industry)
350
Enrollment
10
Locations
24
Arms
108
Anticipated Duration (Months)
35
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
350 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Nov 15, 2013
Actual Primary Completion Date :
Feb 19, 2019
Anticipated Study Completion Date :
Nov 15, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A: Dose Escalation Cohort 1

Pegilodecakin (1 ug/kg) - Daily subcutaneous (SC) injections of pegilodecakin for up to 22 months

Drug: Pegilodecakin
Daily subcutaneous injections of pegilodecakin up to 12 months
Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    		•
    Experimental: Part A: Dose Escalation Cohort 2

    Pegilodecakin (2.5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    		•
    Experimental: Part A: Dose Escalation Cohort 3

    Pegilodecakin (5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    		•
    Experimental: Part A: Dose Escalation Cohort 4

    Pegilodecakin (10 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    		•
    Experimental: Part A: Dose Escalation Cohort 5

    Pegilodecakin (20 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    		•
    Experimental: Part A: Dose Escalation Cohort 6

    Pegilodecakin (40 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    		•
    Experimental: Part A: Dose Expansion Cohort 1

    at least 15 RCC participants will be dosed with pegilodecakin for up to 22 months

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    		•
    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

    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 Names:
  • Taxol or taxotere and paraplatin or platinol

    		•
    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

    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 Names:
  • Taxol or taxotere and paraplatin or platinol

    		•
    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

    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 Names:
  • Taxol or taxotere and paraplatin or platinol

    		•
    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

    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 Names:
  • Taxol or taxotere and paraplatin or platinol

    		•
    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

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
    Intravenous administration on Day 1 and 2 of every 14 day cycle
    Other Names:
  • Eloxatin®/Leucovorin/5-FU

    		•
    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

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
    Intravenous administration on Day 1 and 2 of every 14 day cycle
    Other Names:
  • Eloxatin®/Leucovorin/5-FU

    		•
    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

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
    Intravenous administration on Day 1 and 2 of every 14 day cycle
    Other Names:
  • Eloxatin®/Leucovorin/5-FU

    		•
    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

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    • Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
    Intravenous administration on Day 1 and 2 of every 14 day cycle
    Other Names:
  • Eloxatin®/Leucovorin/5-FU

    		•
    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.

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    • 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 Names:
  • Gemzar/Abraxane ABI-007

    		•
    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

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    • Drug: Capecitabine
    Capecitabine will be administered orally twice daily for 14 days out of every 21 days.
    Other Names:
  • Xeloda

    		•
    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

    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
    Paclitaxel will be administered intravenously on Days 1, 8, 15 of each cycle (28 days= 1 cycle) • Paclitaxel 80 mg/ m2 IV
    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

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    • Drug: Pazopanib
    Pazopanib will be administered orally daily continuously
    Other Names:
  • GW786034

    		•
    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

    Drug: Pegilodecakin
    Daily subcutaneous injections of pegilodecakin up to 12 months
    Other Names:
  • LY3500518
  • AM0010
  • PEGylated recombinant human Interleukin-10
  • PEG-rHuIL-10

    • Drug: Pembrolizumab
    Pembrolizumab will be administered intravenously on Day 1 of every 21 day cycle.
    Other Names:
  • Keytruda, MK-3475

    		•
    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

    Drug: nivolumab
    Nivolumab on Day 1 of each cycle (14 days = 1 cycle)
    Other Names:
  • Keytruda

    		•
    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

    Drug: Pembrolizumab
    Pembrolizumab will be administered intravenously on Day 1 of every 21 day cycle.
    Other Names:
  • Keytruda, MK-3475

    		•
    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

    Drug: Pembrolizumab
    Pembrolizumab will be administered intravenously on Day 1 of every 21 day cycle.
    Other Names:
  • Keytruda, MK-3475

    		•
    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

    Drug: Gemcitabine/carboplatin
    gemcitabine and carboplatin on Days 1, 8 of each cycle (21 days = 1 cycle)
    Other Names:
  • gemzar/paraplatin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety and tolerability as measured by incidence of adverse events [up to 12 months]

    2. Pharmacokinetic (PK) parameters [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).

    Secondary Outcome Measures

    1. Change in tumor burden measured by volumetric Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) according to immune-related response criteria (irRC) [up to 12 months]

    2. Progression in bone by bone scintigraphy according to Prostate Cancer Working Group 2 (PCWG2) for participants with metastatic castration resistant prostate cancer (CRPC) [approximatley 4 months]

    3. Anti-Pegilodecakin antibody formation [up to 12 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCLA Medical Hematology & Oncology Los Angeles California United States 90024
    2 UCSF San Francisco California United States
    3 Sarah Cannon Research Institute at HealthONE Denver Colorado United States 80218
    4 Florida Cancer Specialists & Research Institute Sarasota Florida United States 34232
    5 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    6 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    7 Stephenson Cancer Center at Oklahoma University TSET Phase 1 Program Oklahoma City Oklahoma United States 73104
    8 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    9 The University of Texas M.D. Anderson Cancer Center Houston Texas United States 77030
    10 South Texas Accelerated Research Therapeutics San Antonio Texas United States 78229

    Sponsors and Collaborators

    • Eli Lilly and Company
    • ARMO BioSciences

    Investigators

    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02009449
    Other Study ID Numbers:
    • 17159
    • J1L-AM-JZGA
    • AM0010-001
    First Posted:
    Dec 12, 2013
    Last Update Posted:
    Sep 5, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Eli Lilly and Company
    Phase 1/Phase 1b
    Oncology
    Cancer
    Solid Tumors
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Renal Cell
    Colorectal Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Pancreatic Neoplasms
    Leucovorin
    Gemcitabine
    Paclitaxel
    Docetaxel
    Albumin-Bound Paclitaxel
    Carboplatin
    Pembrolizumab
    Fluorouracil
    Capecitabine
    Oxaliplatin
    Nivolumab
    Levoleucovorin

    Study Results

    No Results Posted as of Sep 5, 2021