UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma
- Conditions
- Malignant Melanoma
- Interventions
- Registration Number
- NCT04382664
- Lead Sponsor
- Ultimovacs ASA
- Brief Summary
This is a randomized, open label study to investigate efficacy and safety of UV1 vaccination in combination with nivolumab and ipilimumab as first line treatment of adult patients with histologically confirmed unresectable metastatic melanoma.
- Detailed Description
This is a randomized, open label study to investigate efficacy and safety of UV1 vaccination in combination with nivolumab and ipilimumab as first line treatment of adult patients with histologically confirmed unresectable metastatic melanoma.
Patients in the experimental arm will receive 8 UV1 vaccinations over 4 cycles of nivolumab and ipilimumab. Patients in the control arm will receive 4 cycles of nivolumab and ipilimumab. Patients in both arms will start maintenance therapy 6 weeks after the last dose of induction therapy, nivolumab at a dose of 480 mg every 4 weeks.
All patients will be followed up until death or until the end of the study.
To support the Extended Exploratory Cohort of the study, an additional 20 patients at selected sites will be enrolled in a single arm UV1 cohort for collection of additional biological material. These patients are in addition to the 156 randomized patients in the main part of the study and will not be included in the main analysis of the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 156
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Male or female patients at least 18 years of age at the time of signing the ICF.
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Histologically confirmed diagnosis of unresectable stage IIIB D, or unresectable stage IV malignant melanoma.
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Eligible for combination treatment with nivolumab and ipilimumab.
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An ECOG performance status of 0 or 1.
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Adequate organ function as indicated by the following laboratory values:
Hematological
- Absolute neutrophil count ≥1,500/µL
- Platelet count ≥100 x 103/µL
- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L Renal
- Creatinine ≤1.5 x upper limit of normal (ULN) Hepatic
- Total bilirubin ≤1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 ULN
- Aspartate aminotransferase/serum glutamic oxaloacetic transaminase and alanine aminotransferase/serum glutamic pyruvic transaminase ≤2.5 x ULN for patients without liver metastasis or ≤5 x ULN for patients with liver metastasis.
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Male patients who are sexually active with a female of childbearing potential must agree to use an adequate method of contraception.
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Women of childbearing potential (WOCBP) must have a negative urine or serum/plasma pregnancy test.
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WOCBP must use adequate contraception.
- Previous non melanoma malignancies unless curatively treated and complete remission was achieved at least 2 years prior to randomization. Patients with prior curatively treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or carcinoma in situ of the breast, or other in situ cancers are allowed irrespective of time passed since curative treatment. Patients with prior completely resected malignant melanoma are also allowed.
- Known brain metastases or leptomeningeal metastases. If a patient experiences neurological symptoms indicative of brain metastases, a brain MRI should be performed.
- Diagnosis of uveal or ocular melanoma.
- Known history or any evidence of active, non-infectious pneumonitis.
- History of New York Heart Association class 3-4 congestive heart failure or history of myocardial infarction within 6 months of starting induction therapy.
- Active infection requiring systemic treatment.
- Diagnosis of immunodeficiency.
- Known history of severe hypersensitivity reactions to nivolumab, ipilimumab, sargramostim, or their excipients.
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- History of or active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (hepatitis C virus antibody).
- Women who are breastfeeding.
- Prior systemic treatment for unresectable stage IIIB D or unresectable stage IV malignant melanoma.
- Systemic corticosteroid treatment (doses exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive treatment within 7 days prior to the first dose of induction therapy.
- Receipt of a live vaccine within 30 days prior to start of induction therapy.
- Receipt of any other investigational treatment within 4 weeks of the first dose of induction therapy.
- Any medical, psychological, or social condition that would make it difficult for the patient to participate in the study and comply with the study procedures, restrictions and requirements.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description UV1 vaccination + nivolumab and ipilimumab UV1 UV1 vaccination + nivolumab and ipilimumab UV1 vaccination + nivolumab and ipilimumab Sargramostim UV1 vaccination + nivolumab and ipilimumab UV1 vaccination + nivolumab and ipilimumab Ipilimumab UV1 vaccination + nivolumab and ipilimumab UV1 vaccination + nivolumab and ipilimumab Nivolumab UV1 vaccination + nivolumab and ipilimumab Nivolumab and ipilimumab Ipilimumab Nivolumab and ipilimumab Nivolumab and ipilimumab Nivolumab Nivolumab and ipilimumab UV1 vaccination + nivolumab and ipilimumab UV1 UV1 vaccination + nivolumab and ipilimumab Nivolumab and ipilimumab Nivolumab nivolumab and ipilimumab UV1 vaccination + nivolumab and ipilimumab Sargramostim UV1 vaccination + nivolumab and ipilimumab UV1 vaccination + nivolumab and ipilimumab Ipilimumab UV1 vaccination + nivolumab and ipilimumab Nivolumab and ipilimumab Ipilimumab nivolumab and ipilimumab UV1 vaccination + nivolumab and ipilimumab Nivolumab UV1 vaccination + nivolumab and ipilimumab
- Primary Outcome Measures
Name Time Method PFS Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (by Blinded Independent Central Review (BICR) Time from randomization to progressive disease (PD) or death from any cause (approximately 44 months) Compare progression free survival (PFS) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab
- Secondary Outcome Measures
Name Time Method Overall Survival Time from randomization to death from any cause /follow-up until 70 PFS events/18 months post rand, approximately 44 months. Compare Overall Survival of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab .
ORR Per RECIST 1.1 Number of complete and partial responses during the study, approximately 44 months. Compare the objective response rate (ORR) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab.
DOR Per RECIST 1.1 Time from first CR or PR to PD or death from any cause, approximately 44 months. Compare duration of response (DOR) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab.
Evaluation of Adverse Events, Vital Signs, Laboratory Assessments and ECOG Performance Status Time from randomization to end of study, approximately 47 months. Compare the safety of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab. Safety will be listed and summarized descriptively by treatment arm comparing number of participants with observation and changes from baseline and at each visit related to AEs, deaths, vital signs (weight (kg), systolic and diastolic blood pressure (mmHg), pulse rate (bpm), body temperature (°C)), laboratory assessments and ECOG performance status (Grade 0 - Grade 5).
Trial Locations
- Locations (37)
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
California Cancer Associates for Research & Excellence (CCARE
🇺🇸San Marcos, California, United States
University of California Irvine Health
🇺🇸Orange, California, United States
Saint John's Health Center - John Wayne Cancer Institute (JWCI)
🇺🇸Santa Monica, California, United States
Holy Cross Medical Group
🇺🇸Fort Lauderdale, Florida, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Rush University Medical Center - Rush University Cancer Center
🇺🇸Chicago, Illinois, United States
NorthShore University Research Institute
🇺🇸Evanston, Illinois, United States
Oncology Specialists, S.C.
🇺🇸Park Ridge, Illinois, United States
State University of New York (SUNY) Upstate Medical University
🇺🇸New York, New York, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Antwerp University Hospital
🇧🇪Antwerp, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussel, Belgium
Sørlandet Sykehus HF(SSHF)
🇳🇴Kristiansand, Norway
St. Olavs Hospital HF
🇳🇴Trondheim, Norway
Velindre NHS Trust
🇬🇧Cardiff, United Kingdom
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Oxford University Hospitals NHS Trust - Churchill Hospital
🇬🇧Oxford, United Kingdom
Cancer Research UK Manchester Institute
🇬🇧Manchester, United Kingdom
The Royal Free London NHS Foundation Trust - The Royal Free Hospital
🇬🇧London, United Kingdom
Universitetssykehuset Nord-Norge HF
🇳🇴Tromsø, Norway
Ålesund Hospital- Helse Sunnmore HF
🇳🇴Ålesund, Norway
Sykehuset Østfold HF
🇳🇴Gralum, Norway
Oslo University Hospital - The Norwegian Radium Hospital
🇳🇴Oslo, Norway
Stavanger University Hospital
🇳🇴Stavanger, Norway
NorthShore University HealthSystem
🇺🇸Greenville, South Carolina, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Nebraska Cancer Specialists- Midwest Cancer Center
🇺🇸Papillion, Nebraska, United States
University of Rochester
🇺🇸Rochester, New York, United States
Leuven University Hospital
🇧🇪Leuven, Belgium
GZA Hospital Sint-Augustinus
🇧🇪Wilrijk, Belgium
Royal Marsden Hospital - Institute of Cancer Research - Chelsea
🇬🇧London, United Kingdom
Ridley-Tree Cancer Center
🇺🇸Santa Barbara, California, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States