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

Lilly

Status and phase: Completed; 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: Capecitabine; Drug: Gemcitabine/carboplatin; Drug: gemcitabine/nab-paclitaxel; Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil); Drug: nivolumab; Drug: Pazopanib; Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin; Drug: Pembrolizumab; Drug: Paclitaxel; 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: 353 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)

---

353 participants in 23 patient groups

Part A: Pegilodecakin 0.08/0.1 mg

Experimental group

Description:

Participants received 0.08 or 0.1 mg of Pegilodecakin once daily (QD) administered subcutaneously (SC). Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Part A: Pegilodecakin 0.2/0.25 mg

Experimental group

Description:

Participants received 0.2 or 0.25 mg of Pegilodecakin QD administered SC. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Part A: Pegilodecakin 0.4/0.5 mg

Experimental group

Description:

Participants received 0.4 or 0.5 mg of Pegilodecakin QD administered SC. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Part A: Pegilodecakin 0.8/1 mg

Experimental group

Description:

Participants received 0.8 or 1 mg of Pegilodecakin QD administered SC. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Part A: Pegilodecakin 1.6/2 mg

Experimental group

Description:

Participants received 1.6 or 2 mg of Pegilodecakin QD administered SC. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Part A: Pegilodecakin 3.2/4 mg

Experimental group

Description:

Participants received 3.2 or 4 mg of Pegilodecakin QD administered SC. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Part B: Pegilodecakin 0.2/0.25 mg + Platinum/Taxane

Experimental group

Description:

Participants received 0.2 or 0.25 mg of Pegilodecakin QD administered SC along with Platinum/Taxane combination on Day 1 of each 21-day cycle for a maximum of 5 or 6 cycles. Participants received: Paclitaxel 200 or 175 mg/m² intravenously (IV) over 3 hours, or docetaxel 75 or 65 mg/m² IV over 1 hour, followed by carboplatin (AUC 6/5/4; max 6 × 150 mg) IV over 30 minutes or cisplatin 75 mg/m² IV over 6-8 hours. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Part B: Pegilodecakin 0.4/0.5 mg + Platinum/Taxane

Experimental group

Description:

Participants received 0.4 or 0.5 mg of Pegilodecakin QD administered SC along with Platinum/Taxane combination on Day 1 of each 21-day cycle for a maximum of 5 or 6 cycles. Participants received: Paclitaxel 200 or 175 mg/m² intravenously (IV) over 3 hours, or docetaxel 75 or 65 mg/m² IV over 1 hour, followed by carboplatin (AUC 6/5/4; max 6 × 150 mg) IV over 30 minutes or cisplatin 75 mg/m² IV over 6-8 hours. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Part B: Pegilodecakin 0.8/1 mg + Platinum/Taxane

Experimental group

Description:

Participants received 0.8 or 1 mg of Pegilodecakin QD administered SC along with Platinum/Taxane combination on Day 1 of each 21-day cycle for a maximum of 5 or 6 cycles. Participants received: Paclitaxel 200 or 175 mg/m² intravenously (IV) over 3 hours, or docetaxel 75 or 65 mg/m² IV over 1 hour, followed by carboplatin (AUC 6/5/4; max 6 × 150 mg) IV over 30 minutes or cisplatin 75 mg/m² IV over 6-8 hours. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin

Part C: Pegilodecakin 0.2/0.25 mg + FOLFOX

Experimental group

Description:

Participants received 0.2 or 0.25 mg of Pegilodecakin QD administered SC and FOLFOX treatment on Day 1 of each 14-day cycle for a maximum of 12 cycles. Participants received: oxaliplatin 85 mg/m2 IV over 2 hours, and leucovorin 200 mg/m2 IV over 2 hours, followed by 5-Fluorouracil (FU) 400 mg/m2 IV bolus over 2-4 minutes, 5-FU 600 mg/m2/day IV over 22 hours, and leucovorin 200 mg/m2 over 2 hours on Day 2 followed by 5-FU 400 mg/m2 IV bolus over 2-4 minutes, and 5-FU 600 mg/m2/day IV over 22 hours. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

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

Part C: Pegilodecakin 0.4/0.5 mg + FOLFOX

Experimental group

Description:

Participants received 0.4 or 0.5 mg of Pegilodecakin QD administered SC and FOLFOX treatment on Day 1 of each 14-day cycle for a maximum of 12 cycles. Participants received: oxaliplatin 85 mg/m2 IV over 2 hours, and leucovorin 200 mg/m2 IV over 2 hours, followed by 5-FU 400 mg/m2 IV bolus over 2-4 minutes, 5-FU 600 mg/m2/day IV over 22 hours, and leucovorin 200 mg/m2 over 2 hours on Day 2 followed by 5-FU 400 mg/m2 IV bolus over 2-4 minutes, and 5-FU 600 mg/m2/day IV over 22 hours. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

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

Part C: Pegilodecakin 0.8/1 mg + FOLFOX

Experimental group

Description:

Participants received 0.8 or 1 mg of Pegilodecakin QD administered SC and FOLFOX treatment on Day 1 of each 14-day cycle for a maximum of 12 cycles. Participants received: oxaliplatin 85 mg/m2 IV over 2 hours, and leucovorin 200 mg/m2 IV over 2 hours, followed by 5-FU 400 mg/m2 IV bolus over 2-4 minutes, 5-FU 600 mg/m2/day IV over 22 hours, and leucovorin 200 mg/m2 over 2 hours on Day 2 followed by 5-FU 400 mg/m2 IV bolus over 2-4 minutes, and 5-FU 600 mg/m2/day IV over 22 hours. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

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

Part D: Pegilodecakin 0.4/ 0.5 mg + Gemcitabine/Nab-Paclitaxel

Experimental group

Description:

Participants received 0.4 or 0.5 mg of Pegilodecakin QD administered SC with Gemcitabine 1000 mg/m2 IV over 30 minutes plus nab-paclitaxel 125 mg/m2 IV over 30 to 40 minutes on Days 1, 8, and 15 of every 28-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: gemcitabine/nab-paclitaxel

Part E: Pegilodecakin 0.8/1 mg + Capecitabine

Experimental group

Description:

Participants received 0.8 or 1 mg of Pegilodecakin QD administered SC with Capecitabine 1000 mg/m² orally twice daily (BID) on Days 1 through 14 of each 21-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Capecitabine

Part F: Pegilodecakin 0.8/ 1 mg + Paclitaxel

Experimental group

Description:

Participants received 0.8 or 1 mg of Pegilodecakin QD administered SC with Paclitaxel 80 mg/m2 IV over 3 hours on Days 1, 8, and 15 of every 28-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Paclitaxel

Part G: Pegilodecakin 0.8/1 mg + Pazopanib

Experimental group

Description:

Participants received a 0.8 or 1 mg of Pegilodecakin QD administered SC with Pazopanib 800 mg orally QD. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Pazopanib

Part H: Pegilodecakin 0.8/1 mg + Pembrolizumab

Experimental group

Description:

Participants received 0.8 or 1 mg of Pegilodecakin QD administered SC with Pembrolizumab 2 mg/kg bolus IV infusion over 30 minutes on Day 1 of each 21-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Pembrolizumab

Part H: Pegilodecakin 1.6/2 mg + Pembrolizumab

Experimental group

Description:

Participants received 1.6 or 2 mg of Pegilodecakin QD administered SC with Pembrolizumab 2 mg/kg bolus IV infusion over 30 minutes on Day 1 of each 21-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Pembrolizumab

Part H: Pegilodecakin 3.2/4 mg + Pembrolizumab

Experimental group

Description:

Participants received 3.2 or 4 mg of Pegilodecakin QD administered SC with Pembrolizumab 2 mg/kg bolus IV infusion over 30 minutes on Day 1 of each 21-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Pembrolizumab

Part J: Pegilodecakin 0.8/1 mg + Gemcitabine/Carboplatin

Experimental group

Description:

Participants received 0.8 or 1 mg of Pegilodecakin QD administered SC with gemcitabine 500 mg/m2 IV over 30 minutes followed by carboplatin targeting an Area Under the Curve of 2 mg/mL x min (AUC2) IV over 60 minutes on Days 1 and 8 of each 21-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Gemcitabine/carboplatin

Part I: Pegilodecakin 1.6/2 mg + Nivolumab

Experimental group

Description:

Participants received 1.6 or 2 mg of Pegilodecakin QD administered SC with Nivolumab 3 mg/kg IV infusion over 60 minutes on Day 1 of each 14-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: nivolumab

Part I: Pegilodecakin 0.8/1 mg + Nivolumab

Experimental group

Description:

Participants received 0.8 or 1 mg of Pegilodecakin QD administered SC with Nivolumab 3 mg/kg IV infusion over 60 minutes on Day 1 of each 14-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: nivolumab

Part J: Pegilodecakin 0.4/0.5 mg + Gemcitabine/Carboplatin

Experimental group

Description:

Participants received 0.4 or 0.5 mg of Pegilodecakin QD administered SC with gemcitabine 500 mg/m2 IV over 30 minutes followed by carboplatin targeting an AUC2 IV over 60 minutes on Days 1 and 8 of each 21-day cycle. Study treatment continued until disease progression, death, unacceptable toxicity, or end of trial.

Treatment:

Drug: Pegilodecakin

Drug: Gemcitabine/carboplatin