A Phase 1 Study of Pegilodecakin (LY3500518) in Participants With Advanced Solid Tumors
Phase 1
Completed
- Conditions
- Prostate CancerPancreatic CarcinomaSolid TumorsBreast CancerMelanomaRenal Cell CarcinomaNon-small Cell Lung CarcinomaOvarian CancerColorectal Carcinoma
- Interventions
- Drug: Gemcitabine/carboplatinDrug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)Drug: gemcitabine/nab-paclitaxel
- Registration Number
- NCT02009449
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 353
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part B: Dose Expansion Cohort Paclitaxel or Docetaxel and Carboplatin or Cisplatin 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 Part B: Dose Escalation Cohort 2 Paclitaxel or Docetaxel and Carboplatin or Cisplatin 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 Part C: Dose Escalation Cohort 1 FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil) 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 Part C: Dose Expansion Cohort 1 FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil) 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 Part B: Dose Escalation Cohort 1 Paclitaxel or Docetaxel and Carboplatin or Cisplatin 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 Part C: Dose Escalation Cohort 3 FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil) 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 Part D: Dose Escalation Cohort 1 gemcitabine/nab-paclitaxel 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. Part B: Dose Escalation Cohort 3 Paclitaxel or Docetaxel and Carboplatin or Cisplatin 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 Part C: Dose Escalation Cohort 2 FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil) 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 Part J: Dose Escalation Cohort 1 Gemcitabine/carboplatin 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 Part A: Dose Escalation Cohort 3 Pegilodecakin Pegilodecakin (5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months Part C: Dose Escalation Cohort 3 Pegilodecakin 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 Part E: Dose Escalation Cohort 1 Capecitabine 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 Part F: Dose Escalation Cohort 1 Pegilodecakin 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 Part G: Dose Escalation Cohort 1 Pazopanib 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 Part F: Dose Escalation Cohort 1 Paclitaxel 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 Part H: Dose Escalation Cohort 1 Pembrolizumab 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 Part I: Dose Escalation Cohort 1 nivolumab 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 Part H: Dose Escalation Cohort 2 Pembrolizumab 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 Part H: Dose Escalation Cohort 3 Pembrolizumab 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 Part A: Dose Escalation Cohort 1 Pegilodecakin Pegilodecakin (1 ug/kg) - Daily subcutaneous (SC) injections of pegilodecakin for up to 22 months Part A: Dose Escalation Cohort 2 Pegilodecakin Pegilodecakin (2.5 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months Part A: Dose Escalation Cohort 4 Pegilodecakin Pegilodecakin (10 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months Part A: Dose Escalation Cohort 5 Pegilodecakin Pegilodecakin (20 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months Part A: Dose Escalation Cohort 6 Pegilodecakin Pegilodecakin (40 ug/kg) - Daily subcutaneous injections of pegilodecakin for up to 22 months Part A: Dose Expansion Cohort 1 Pegilodecakin at least 15 RCC participants will be dosed with pegilodecakin for up to 22 months Part B: Dose Escalation Cohort 1 Pegilodecakin 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 Part B: Dose Escalation Cohort 3 Pegilodecakin 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 Part B: Dose Escalation Cohort 2 Pegilodecakin 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 Part B: Dose Expansion Cohort Pegilodecakin 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 Part C: Dose Escalation Cohort 2 Pegilodecakin 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 Part C: Dose Escalation Cohort 1 Pegilodecakin 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 Part C: Dose Expansion Cohort 1 Pegilodecakin 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 Part D: Dose Escalation Cohort 1 Pegilodecakin 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. Part E: Dose Escalation Cohort 1 Pegilodecakin 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 Part G: Dose Escalation Cohort 1 Pegilodecakin 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 Part H: Dose Escalation Cohort 1 Pegilodecakin 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
- Primary Outcome Measures
Name Time Method Pharmacokinetic (PK) parameters 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 up to 12 months
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (10)
UCLA Medical Hematology & Oncology
🇺🇸Los Angeles, California, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Florida Cancer Specialists & Research Institute
🇺🇸Sarasota, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics
🇺🇸San Antonio, Texas, United States
UCSF
🇺🇸San Francisco, California, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
Stephenson Cancer Center at Oklahoma University TSET Phase 1 Program
🇺🇸Oklahoma City, Oklahoma, United States