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

Lilly

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Drug: gemcitabine/nab-paclitaxel; Drug: Capecitabine; Drug: nivolumab; Drug: Gemcitabine/carboplatin; Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil); Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin; Drug: Paclitaxel; Drug: Pembrolizumab; Drug: Pazopanib; Drug: Pegilodecakin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02009449

J1L-AM-JZGA (Other Identifier)

AM0010-001 (Other Identifier)

17159

Details and patient eligibility

About

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.

Enrollment: 350 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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350 participants in 24 patient groups

Part A: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 2

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 3

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 4

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 5

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Part A: Dose Escalation Cohort 6

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Part A: Dose Expansion Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Part B: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Part B: Dose Escalation Cohort 2

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Part B: Dose Escalation Cohort 3

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Part B: Dose Expansion Cohort

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Part C: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

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

Part C: Dose Escalation Cohort 2

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

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

Part C: Dose Escalation Cohort 3

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

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

Part C: Dose Expansion Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

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

Part D: Dose Escalation Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: Pegilodecakin

Drug: gemcitabine/nab-paclitaxel

Part E: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Drug: Capecitabine

Part F: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel

Part G: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pazopanib

Drug: Pegilodecakin

Part H: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Pegilodecakin

Drug: Pembrolizumab

Part I: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: nivolumab

Part H: Dose Escalation Cohort 2

Experimental group

Description:

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

Treatment:

Drug: Pembrolizumab

Part H: Dose Escalation Cohort 3

Experimental group

Description:

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

Treatment:

Drug: Pembrolizumab

Part J: Dose Escalation Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Gemcitabine/carboplatin