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

Study Overview
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Brief Summary
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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.

Official Title
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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

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

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Dose Escalation Cohort 1<br>Pegilodecakin (1 ug/kg) - Daily subcutaneous (SC) injections of pegilodecakin for up to 22 months | Drug: Pegilodecakin<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;|
| Experimental: Part A: Dose Escalation Cohort 2<br>Pegilodecakin (2.5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months | Drug: Pegilodecakin<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;|
| Experimental: Part A: Dose Escalation Cohort 3<br>Pegilodecakin (5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months | Drug: Pegilodecakin<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;|
| Experimental: Part A: Dose Escalation Cohort 4<br>Pegilodecakin (10 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months | Drug: Pegilodecakin<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;|
| Experimental: Part A: Dose Escalation Cohort 5<br>Pegilodecakin (20 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months | Drug: Pegilodecakin<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;|
| Experimental: Part A: Dose Escalation Cohort 6<br>Pegilodecakin (40 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months | Drug: Pegilodecakin<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;|
| Experimental: Part A: Dose Expansion Cohort 1<br>at least 15 RCC participants will be dosed with pegilodecakin for up to 22 months | Drug: Pegilodecakin<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;|
| Experimental: Part B: Dose Escalation Cohort 1<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin<br>* Day 1 of every 21 day cycle<br>* Other names: Taxol or taxotere and paraplatin or platinol;|
| Experimental: Part B: Dose Escalation Cohort 2<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin<br>* Day 1 of every 21 day cycle<br>* Other names: Taxol or taxotere and paraplatin or platinol;|
| Experimental: Part B: Dose Escalation Cohort 3<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin<br>* Day 1 of every 21 day cycle<br>* Other names: Taxol or taxotere and paraplatin or platinol;|
| Experimental: Part B: Dose Expansion Cohort<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: Paclitaxel or Docetaxel and Carboplatin or Cisplatin<br>* Day 1 of every 21 day cycle<br>* Other names: Taxol or taxotere and paraplatin or platinol;|
| Experimental: Part C: Dose Escalation Cohort 1<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)<br>* Intravenous administration on Day 1 and 2 of every 14 day cycle<br>* Other names: Eloxatin®/Leucovorin/5-FU;|
| Experimental: Part C: Dose Escalation Cohort 2<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)<br>* Intravenous administration on Day 1 and 2 of every 14 day cycle<br>* Other names: Eloxatin®/Leucovorin/5-FU;|
| Experimental: Part C: Dose Escalation Cohort 3<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)<br>* Intravenous administration on Day 1 and 2 of every 14 day cycle<br>* Other names: Eloxatin®/Leucovorin/5-FU;|
| Experimental: Part C: Dose Expansion Cohort 1<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)<br>* Intravenous administration on Day 1 and 2 of every 14 day cycle<br>* Other names: Eloxatin®/Leucovorin/5-FU;|
| Experimental: Part D: Dose Escalation Cohort 1<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: gemcitabine/nab-paclitaxel<br>* Intravenous administration of the gemcitabine/nab-paclitaxel regimen on Day 1, 8 and 15 of each 28 day treatment cycle.<br>* Other names: Gemzar/Abraxane ABI-007;|
| Experimental: Part E: Dose Escalation Cohort 1<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: Capecitabine<br>* Capecitabine will be administered orally twice daily for 14 days out of every 21 days.<br>* Other names: Xeloda;|
| Experimental: Part F: Dose Escalation Cohort 1<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: Paclitaxel<br>* Paclitaxel will be administered intravenously on Days 1, 8, 15 of each cycle (28 days= 1 cycle) • Paclitaxel 80 mg/ m2 IV<br>|
| Experimental: Part G: Dose Escalation Cohort 1<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: Pazopanib<br>* Pazopanib will be administered orally daily continuously<br>* Other names: GW786034;|
| Experimental: Part H: Dose Escalation Cohort 1<br>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<br>* Daily subcutaneous injections of pegilodecakin up to 12 months<br>* Other names: PEG-rHuIL-10;Drug: Pembrolizumab<br>* Pembrolizumab will be administered intravenously on Day 1 of every 21 day cycle.<br>* Other names: Keytruda, MK-3475;|
| Experimental: Part I: Dose Escalation Cohort 1<br>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<br>* Nivolumab on Day 1 of each cycle (14 days = 1 cycle)<br>* Other names: Keytruda;|
| Experimental: Part H: Dose Escalation Cohort 2<br>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<br>* Pembrolizumab will be administered intravenously on Day 1 of every 21 day cycle.<br>* Other names: Keytruda, MK-3475;|
| Experimental: Part H: Dose Escalation Cohort 3<br>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<br>* Pembrolizumab will be administered intravenously on Day 1 of every 21 day cycle.<br>* Other names: Keytruda, MK-3475;|
| Experimental: Part J: Dose Escalation Cohort 1<br>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<br>* gemcitabine and carboplatin on Days 1, 8 of each cycle (21 days = 1 cycle)<br>* Other names: gemzar/paraplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Phase 1/Phase 1b, Oncology, Solid Tumors