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
Overview
- Phase
- Phase 1
- Intervention
- Pegilodecakin
- Conditions
- Melanoma
- Sponsor
- Eli Lilly and Company
- Enrollment
- 353
- Locations
- 10
- Primary Endpoint
- Pharmacokinetic (PK) parameters
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
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
Arms & Interventions
Part A: Dose Escalation Cohort 1
Pegilodecakin (1 ug/kg) - Daily subcutaneous (SC) injections of pegilodecakin for up to 22 months
Intervention: Pegilodecakin
Part A: Dose Escalation Cohort 2
Pegilodecakin (2.5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
Intervention: Pegilodecakin
Part A: Dose Escalation Cohort 3
Pegilodecakin (5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
Intervention: Pegilodecakin
Part A: Dose Escalation Cohort 4
Pegilodecakin (10 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
Intervention: Pegilodecakin
Part A: Dose Escalation Cohort 5
Pegilodecakin (20 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
Intervention: Pegilodecakin
Part A: Dose Escalation Cohort 6
Pegilodecakin (40 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months
Intervention: Pegilodecakin
Part A: Dose Expansion Cohort 1
at least 15 RCC participants will be dosed with pegilodecakin for up to 22 months
Intervention: Pegilodecakin
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
Intervention: Pegilodecakin
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
Intervention: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
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
Intervention: Pegilodecakin
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
Intervention: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
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
Intervention: Pegilodecakin
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
Intervention: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
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
Intervention: Pegilodecakin
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
Intervention: Paclitaxel or Docetaxel and Carboplatin or Cisplatin
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
Intervention: Pegilodecakin
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
Intervention: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
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
Intervention: Pegilodecakin
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
Intervention: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
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
Intervention: Pegilodecakin
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
Intervention: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
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
Intervention: Pegilodecakin
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
Intervention: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)
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.
Intervention: Pegilodecakin
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.
Intervention: gemcitabine/nab-paclitaxel
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
Intervention: Pegilodecakin
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
Intervention: Capecitabine
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
Intervention: Pegilodecakin
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
Intervention: Paclitaxel
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
Intervention: Pegilodecakin
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
Intervention: Pazopanib
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
Intervention: Pegilodecakin
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
Intervention: Pembrolizumab
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
Intervention: nivolumab
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
Intervention: Pembrolizumab
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
Intervention: Pembrolizumab
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
Intervention: Gemcitabine/carboplatin
Outcomes
Primary Outcomes
Pharmacokinetic (PK) parameters
Time Frame: up to 12 months
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).
Safety and tolerability as measured by incidence of adverse events
Time Frame: up to 12 months
Secondary Outcomes
- 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)
- 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)
- Anti-Pegilodecakin antibody formation(up to 12 months)