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

NCT02009449 | Completed Phase 1 FDA Drug

• 3 other identifiers: 17159J1L-AM-JZGAAM0010-001
• Study Type: interventional
• Target: 353
• Locations: 1 country
• Sites: 10

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

Keywords

Phase 1/Phase 1b; Oncology; Cancer; Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability as measured by incidence of adverse events

  up to 12 months

• Pharmacokinetic (PK) parameters

  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).

  up to 12 months

Secondary Outcomes (3)

• 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

• 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

• Anti-Pegilodecakin antibody formation

  up to 12 months

Study Arms (24)

Part A: Dose Escalation Cohort 1

EXPERIMENTAL

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

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 2

EXPERIMENTAL

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

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 3

EXPERIMENTAL

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

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 4

EXPERIMENTAL

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

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 5

EXPERIMENTAL

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

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 6

EXPERIMENTAL

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

Drug: Pegilodecakin

Part A: Dose Expansion Cohort 1

EXPERIMENTAL

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

Drug: Pegilodecakin

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

Drug: Pegilodecakin; Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

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

Drug: Pegilodecakin; Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

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

Drug: Pegilodecakin; Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

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

Drug: Pegilodecakin; Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

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

Drug: Pegilodecakin; Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

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

Drug: Pegilodecakin; Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

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

Drug: Pegilodecakin; Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

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

Drug: Pegilodecakin; Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

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.

Drug: Pegilodecakin; Drug: gemcitabine/nab-paclitaxel

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

Drug: Pegilodecakin; Drug: Capecitabine

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

Drug: Pegilodecakin; Drug: Paclitaxel

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

Drug: Pegilodecakin; Drug: Pazopanib

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

Drug: Pegilodecakin; Drug: Pembrolizumab

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

Drug: nivolumab

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

Drug: Pembrolizumab

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

Drug: Pembrolizumab

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

Drug: Gemcitabine/carboplatin

Interventions

Pegilodecakin DRUG

Daily subcutaneous injections of pegilodecakin up to 12 months

Also known as: LY3500518, AM0010, PEGylated recombinant human Interleukin-10, PEG-rHuIL-10

Part A: Dose Escalation Cohort 1; Part A: Dose Escalation Cohort 2; Part A: Dose Escalation Cohort 3; Part A: Dose Escalation Cohort 4; Part A: Dose Escalation Cohort 5; Part A: Dose Escalation Cohort 6; Part A: Dose Expansion Cohort 1; Part B: Dose Escalation Cohort 1; Part B: Dose Escalation Cohort 2; Part B: Dose Escalation Cohort 3; Part B: Dose Expansion Cohort; Part C: Dose Escalation Cohort 1; Part C: Dose Escalation Cohort 2; Part C: Dose Escalation Cohort 3; Part C: Dose Expansion Cohort 1; Part D: Dose Escalation Cohort 1; Part E: Dose Escalation Cohort 1; Part F: Dose Escalation Cohort 1; Part G: Dose Escalation Cohort 1; Part H: Dose Escalation Cohort 1

Paclitaxel or Docetaxel and Carboplatin or Cisplatin DRUG

Day 1 of every 21 day cycle

Also known as: Taxol or taxotere and paraplatin or platinol

Part B: Dose Escalation Cohort 1; Part B: Dose Escalation Cohort 2; Part B: Dose Escalation Cohort 3; Part B: Dose Expansion Cohort

FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil) DRUG

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

Also known as: Eloxatin®/Leucovorin/5-FU

Part C: Dose Escalation Cohort 1; Part C: Dose Escalation Cohort 2; Part C: Dose Escalation Cohort 3; Part C: Dose Expansion Cohort 1

gemcitabine/nab-paclitaxel DRUG

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

Also known as: Gemzar/Abraxane ABI-007

Part D: Dose Escalation Cohort 1

Capecitabine DRUG

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

Also known as: Xeloda

Part E: Dose Escalation Cohort 1

Pazopanib DRUG

Pazopanib will be administered orally daily continuously

Also known as: GW786034

Part G: Dose Escalation Cohort 1

Pembrolizumab DRUG

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

Also known as: Keytruda, MK-3475

Part H: Dose Escalation Cohort 1; Part H: Dose Escalation Cohort 2; Part H: Dose Escalation Cohort 3

Paclitaxel DRUG

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

Part F: Dose Escalation Cohort 1

nivolumab DRUG

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

Also known as: Keytruda

Part I: Dose Escalation Cohort 1

Gemcitabine/carboplatin DRUG

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

Also known as: gemzar/paraplatin

Part J: Dose Escalation Cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• ARMO BioSciences: collaborator

Study Sites (10)

UCLA Medical Hematology & Oncology

Los Angeles, California, 90024, United States

Location

UCSF

San Francisco, California, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists & Research Institute

Sarasota, Florida, 34232, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Stephenson Cancer Center at Oklahoma University TSET Phase 1 Program

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• 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.

  PMID: 31563517 DERIVED

• 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.

  PMID: 27528724 DERIVED

MeSH Terms

Conditions

Melanoma; Prostatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Colorectal Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Neoplasms

Interventions

pegilodecakin; AM0010; Paclitaxel; Docetaxel; Carboplatin; Cisplatin; Folfox protocol; Oxaliplatin; Gemcitabine; Capecitabine; pazopanib; pembrolizumab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Neoplasms, Female; Endocrine System Diseases; Gonadal Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pancreatic Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2013
• First Posted: December 12, 2013
• Study Start: November 15, 2013
• Primary Completion: February 19, 2019
• Study Completion: July 22, 2023
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)