Clinical trial NCT04382664: UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma
Official title: Efficacy and Safety of UV1 Vaccination in Combination With Nivolumab and Ipilimumab as First Line Treatment of Patients With Unresectable or Metastatic Melanoma (INITIUM Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Melanoma
Lead sponsor: Ultimovacs ASA
Sponsor class: INDUSTRY
First posted: 2020-05-11
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients at least 18 years of age at the time of signing the ICF.
2. Histologically confirmed diagnosis of unresectable stage IIIB D, or unresectable stage IV malignant melanoma.
3. Eligible for combination treatment with nivolumab and ipilimumab.
4. An ECOG performance status of 0 or 1.
5. Adequate organ function as indicated by the following laboratory values:

   Hematological
   1. Absolute neutrophil count ≥1,500/µL
   2. Platelet count ≥100 x 103/µL
   3. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L Renal
   4. Creatinine ≤1.5 x upper limit of normal (ULN) Hepatic
   5. Total bilirubin ≤1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels \>1.5 ULN
   6. 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.
6. Male patients who are sexually active with a female of childbearing potential must agree to use an adequate method of contraception.
7. Women of childbearing potential (WOCBP) must have a negative urine or serum/plasma pregnancy test.
8. WOCBP must use adequate contraception.

Exclusion Criteria:

1. 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.
2. Known brain metastases or leptomeningeal metastases. If a patient experiences neurological symptoms indicative of brain metastases, a brain MRI should be performed.
3. Diagnosis of uveal or ocular melanoma.
4. Known history or any evidence of active, non-infectious pneumonitis.
5. History of New York Heart Association class 3-4 congestive heart failure or history of myocardial infarction within 6 months of starting induction therapy.
6. Active infection requiring systemic treatment.
7. Diagnosis of immunodeficiency.
8. Known history of severe hypersensitivity reactions to nivolumab, ipilimumab, sargramostim, or their excipients.
9. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
10. History of or active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (hepatitis C virus antibody).
11. Women who are breastfeeding.
12. Prior systemic treatment for unresectable stage IIIB D or unresectable stage IV malignant melanoma.
13. 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.
14. Receipt of a live vaccine within 30 days prior to start of induction therapy.
15. Receipt of any other investigational treatment within 4 weeks of the first dose of induction therapy.
16. 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.

Primary outcomes:
measure: PFS Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (by Blinded Independent Central Review (BICR)
timeFrame: Time from randomization to progressive disease (PD) or death from any cause (approximately 44 months)
Secondary outcomes:
measure: Overall Survival
timeFrame: Time from randomization to death from any cause /follow-up until 70 PFS events/18 months post rand, approximately 44 months.
measure: ORR Per RECIST 1.1
timeFrame: Number of complete and partial responses during the study, approximately 44 months.
measure: DOR Per RECIST 1.1
timeFrame: Time from first CR or PR to PD or death from any cause, approximately 44 months.
measure: Evaluation of Adverse Events, Vital Signs, Laboratory Assessments and ECOG Performance Status
timeFrame: Time from randomization to end of study, approximately 47 months.
Other outcomes:
measure: Immunological Mechanisms
timeFrame: Time from randomization to end of study to readout of primary objectives, approximately 44 months.
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Orange
country: United States
facility: University of California Irvine Health
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research & Excellence (CCARE
state: California
city: Santa Barbara
country: United States
facility: Ridley-Tree Cancer Center
state: California
city: Santa Monica
country: United States
facility: Saint John's Health Center - John Wayne Cancer Institute (JWCI)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Fort Lauderdale
country: United States
facility: Holy Cross Medical Group
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center - Rush University Cancer Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Research Institute
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, S.C.
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Papillion
country: United States
facility: Nebraska Cancer Specialists- Midwest Cancer Center
state: Nebraska
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: State University of New York (SUNY) Upstate Medical University
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Greenville
country: United States
facility: NorthShore University HealthSystem
state: South Carolina
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Antwerp
country: Belgium
facility: Antwerp University Hospital
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: Leuven University Hospital
city: Wilrijk
country: Belgium
facility: GZA Hospital Sint-Augustinus
city: Gralum
country: Norway
facility: Sykehuset Østfold HF
city: Kristiansand
country: Norway
facility: Sørlandet Sykehus HF(SSHF)
city: Oslo
country: Norway
facility: Oslo University Hospital - The Norwegian Radium Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge HF
city: Trondheim
country: Norway
facility: St. Olavs Hospital HF
city: Ålesund
country: Norway
facility: Ålesund Hospital- Helse Sunnmore HF
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust
city: London
country: United Kingdom
facility: The Royal Free London NHS Foundation Trust - The Royal Free Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Institute of Cancer Research - Chelsea
city: Manchester
country: United Kingdom
facility: Cancer Research UK Manchester Institute
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust - Churchill Hospital
Study officials:
affiliation: University of Colorado Hospital - Anschutz Cancer Pavilion
name: Karl Lewis
role: PRINCIPAL_INVESTIGATOR
References: