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

NCT ID: NCT02009449

Last Updated: 2024-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 353 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-15
• Study Completion Date: 2023-07-22

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.

Conditions

Melanoma; Prostate Cancer; Ovarian Cancer; Renal Cell Carcinoma; Colorectal Carcinoma; Pancreatic Carcinoma; Non-small Cell Lung Carcinoma; Solid Tumors; Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: Dose Escalation Cohort 1

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Part A: Dose Escalation Cohort 2

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Part A: Dose Escalation Cohort 3

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Part A: Dose Escalation Cohort 4

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Part A: Dose Escalation Cohort 5

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Part A: Dose Escalation Cohort 6

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Part A: Dose Expansion Cohort 1

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Intervention Type: DRUG

Day 1 of every 21 day cycle

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Intervention Type: DRUG

Day 1 of every 21 day cycle

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Intervention Type: DRUG

Day 1 of every 21 day cycle

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Intervention Type: DRUG

Day 1 of every 21 day cycle

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

gemcitabine/nab-paclitaxel

Intervention Type: DRUG

Intravenous administration of the gemcitabine/nab-paclitaxel regimen on Day 1, 8 and 15 of each 28 day treatment cycle.

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Capecitabine

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Paclitaxel

Intervention Type: DRUG

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

• Paclitaxel 80 mg/ m2 IV

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Pazopanib

Intervention Type: DRUG

Pazopanib will be administered orally daily continuously

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

Group Type: EXPERIMENTAL

Pegilodecakin

Intervention Type: DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Pembrolizumab

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

nivolumab

Intervention Type: DRUG

Nivolumab on Day 1 of each cycle (14 days = 1 cycle)

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Gemcitabine/carboplatin

Intervention Type: DRUG

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

Interventions

Pegilodecakin

Daily subcutaneous injections of pegilodecakin up to 12 months

Intervention Type: DRUG

Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Day 1 of every 21 day cycle

Intervention Type: DRUG

FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

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

Intervention Type: DRUG

gemcitabine/nab-paclitaxel

Intravenous administration of the gemcitabine/nab-paclitaxel regimen on Day 1, 8 and 15 of each 28 day treatment cycle.

Intervention Type: DRUG

Capecitabine

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

Intervention Type: DRUG

Pazopanib

Pazopanib will be administered orally daily continuously

Intervention Type: DRUG

Pembrolizumab

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

Intervention Type: DRUG

Paclitaxel

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

• Paclitaxel 80 mg/ m2 IV

Intervention Type: DRUG

nivolumab

Nivolumab on Day 1 of each cycle (14 days = 1 cycle)

Intervention Type: DRUG

Gemcitabine/carboplatin

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

Intervention Type: DRUG

Other Intervention Names

LY3500518; AM0010; PEGylated recombinant human Interleukin-10; PEG-rHuIL-10; Taxol or taxotere and paraplatin or platinol; Eloxatin®/Leucovorin/5-FU; Gemzar/Abraxane ABI-007; Xeloda; GW786034; Keytruda, MK-3475; Keytruda; gemzar/paraplatin

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ARMO BioSciences

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

UCLA Medical Hematology & Oncology

Los Angeles, California, United States

UCSF

San Francisco, California, United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Florida Cancer Specialists & Research Institute

Sarasota, Florida, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Stephenson Cancer Center at Oklahoma University TSET Phase 1 Program

Oklahoma City, Oklahoma, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

Countries

United States

References

Naing A, Wong DJ, Infante JR, Korn WM, Aljumaily R, Papadopoulos KP, Autio KA, Pant S, Bauer TM, Drakaki A, Daver NG, Hung A, Ratti N, McCauley S, Van Vlasselaer P, Verma R, Ferry D, Oft M, Diab A, Garon EB, Tannir NM. Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial. Lancet Oncol. 2019 Nov;20(11):1544-1555. doi: 10.1016/S1470-2045(19)30514-5. Epub 2019 Sep 25.

Reference Type: DERIVED

PMID: 31563517 (View on PubMed)

Naing A, Papadopoulos KP, Autio KA, Ott PA, Patel MR, Wong DJ, Falchook GS, Pant S, Whiteside M, Rasco DR, Mumm JB, Chan IH, Bendell JC, Bauer TM, Colen RR, Hong DS, Van Vlasselaer P, Tannir NM, Oft M, Infante JR. Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors. J Clin Oncol. 2016 Oct 10;34(29):3562-3569. doi: 10.1200/JCO.2016.68.1106.

Reference Type: DERIVED

PMID: 27528724 (View on PubMed)

Other Identifiers

J1L-AM-JZGA

Identifier Type: OTHER

Identifier Source: secondary_id

AM0010-001

Identifier Type: OTHER

Identifier Source: secondary_id

17159

Identifier Type: -

Identifier Source: org_study_id