Trial | NCT02009449  Report issue

Title

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

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Active, not recruiting

  • Study Participants

    350
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.
Study Started
Nov 15
2013
Primary Completion
Feb 19
2019
Study Completion
Nov 17
2023
Anticipated
Last Update
Nov 16
2022

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

Drug FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

Intravenous administration on Day 1 and 2 of every 14 day cycle

  • Other names: 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 names: Gemzar/Abraxane ABI-007

Drug Capecitabine

Capecitabine will be administered orally twice daily for 14 days out of every 21 days.

  • Other names: Xeloda

Drug Pazopanib

Pazopanib will be administered orally daily continuously

  • Other names: GW786034

Drug Pembrolizumab

Pembrolizumab will be administered intravenously on Day 1 of every 21 day cycle.

  • Other names: 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 names: Keytruda

Drug Gemcitabine/carboplatin

gemcitabine and carboplatin on Days 1, 8 of each cycle (21 days = 1 cycle)

  • Other names: gemzar/paraplatin

Part A: Dose Escalation Cohort 1 Experimental

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

Part A: Dose Escalation Cohort 2 Experimental

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

Part A: Dose Escalation Cohort 3 Experimental

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

Part A: Dose Escalation Cohort 4 Experimental

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

Part A: Dose Escalation Cohort 5 Experimental

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

Part A: Dose Escalation Cohort 6 Experimental

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

Part A: Dose Expansion Cohort 1 Experimental

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

Part B: Dose Escalation Cohort 1 Experimental

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

Part B: Dose Escalation Cohort 2 Experimental

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

Part B: Dose Escalation Cohort 3 Experimental

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

Part B: Dose Expansion Cohort Experimental

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

Part C: Dose Escalation Cohort 1 Experimental

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

Part C: Dose Escalation Cohort 2 Experimental

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

Part C: Dose Escalation Cohort 3 Experimental

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

Part C: Dose Expansion Cohort 1 Experimental

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

Part D: Dose Escalation Cohort 1 Experimental

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.

Part E: Dose Escalation Cohort 1 Experimental

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

Part F: Dose Escalation Cohort 1 Experimental

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

Part G: Dose Escalation Cohort 1 Experimental

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

Part H: Dose Escalation Cohort 1 Experimental

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

Part I: Dose Escalation Cohort 1 Experimental

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

Part H: Dose Escalation Cohort 2 Experimental

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

Part H: Dose Escalation Cohort 3 Experimental

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

Part J: Dose Escalation Cohort 1 Experimental

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

Criteria 

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
No Results Posted