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CompletedNCT04382664Updated Jan 14, 2025Results posted

UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma

A Phase 2 interventional study of UV1 and Sargramostim in Malignant Melanoma, sponsored by Ultimovacs ASA. Completed at 37 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-01-14.

Sponsored by Ultimovacs ASA · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
156
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Malignant Melanoma

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03

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 519 are open to participants now.

This study's enrollment of 156 is above the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

Ultimovacs ASA is the lead sponsor of 6 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
156 participants (actual)

Study arms

  • Experimental
    UV1 vaccination + nivolumab and ipilimumab

    UV1 vaccination + nivolumab and ipilimumab

    Biological: UV1 · Biological: Sargramostim · Biological: Ipilimumab · Biological: Nivolumab

  • Active comparator
    Nivolumab and ipilimumab

    Nivolumab and ipilimumab

    Biological: Ipilimumab · Biological: Nivolumab

Interventions

  • BiologicalUV1

    UV1 vaccine (300 μg) will be injected intradermally.

  • BiologicalSargramostim

    Sargramostim (75 μg) is used as a vaccine adjuvant.

    Also known as: Leukine

  • BiologicalIpilimumab

    Ipilimumab is dosed according to label.

    Also known as: Yervoy

  • BiologicalNivolumab

    Nivolumab is dosed according to label.

    Also known as: Opdivo

06

What researchers measure

Primary outcomes

  1. PFS Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (by Blinded Independent Central Review (BICR)

    Compare progression free survival (PFS) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab

    Time frame: Time from randomization to progressive disease (PD) or death from any cause (approximately 44 months)

Secondary outcomes

  1. Overall Survival

    Compare Overall Survival of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab .

    Time frame: Time from randomization to death from any cause /follow-up until 70 PFS events/18 months post rand, approximately 44 months.

  2. ORR Per RECIST 1.1

    Compare the objective response rate (ORR) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab.

    Time frame: Number of complete and partial responses during the study, approximately 44 months.

  3. DOR Per RECIST 1.1

    Compare duration of response (DOR) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab.

    Time frame: Time from first CR or PR to PD or death from any cause, approximately 44 months.

  4. Evaluation of Adverse Events, Vital Signs, Laboratory Assessments and ECOG Performance Status

    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).

    Time frame: Time from randomization to end of study, approximately 47 months.

Other outcomes

  1. Immunological Mechanisms

    To elucidate the immunological mechanisms underlying the interplay between immune activation provoked by UV1 vaccination and inhibition of tumor resistance mechanisms and peripheral immune tolerance induced by checkpoint blockade and how biological factors affect the efficacy of the combination therapy. This will be evaluated by change in immune- and tumor-related gene, cell, and protein profiles in blood over time in both treatment arms (analysis of plasma proteins, cell-free plasma DNA, and cellular genomic DNA).

    Time frame: Time from randomization to end of study to readout of primary objectives, approximately 44 months.

07

Results

Posted Jan 14, 2025

Participant flow

Participant flow — Overall Study
MilestoneUV1 Vaccination + Nivolumab and IpilimumabNivolumab and Ipilimumab
Started7878
Completed7576
Not completed32

Outcome measures

PrimaryPFS Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (by Blinded Independent Central Review (BICR)

Compare progression free survival (PFS) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab

Time frame:
Time from randomization to progressive disease (PD) or death from any cause (approximately 44 months)
Reported as:
Count of participants · Participants
PFS Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (by Blinded Independent Central Review (BICR)
ParticipantsUV1 Vaccination + Nivolumab and IpilimumabNivolumab and Ipilimumab
PFS Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (by Blinded Independent Central Review (BICR)3534
Statistical analysis
  • UV1 Vaccination + Nivolumab and Ipilimumab vs Nivolumab and Ipilimumab · Regression, Cox · p = 0.845 · Hazard ratio (hr): 0.95 · 80% CI 0.694 to 1.309
SecondaryOverall Survival

Compare Overall Survival of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab .

Time frame:
Time from randomization to death from any cause /follow-up until 70 PFS events/18 months post rand, approximately 44 months.

Results for this outcome have not been posted.

SecondaryORR Per RECIST 1.1

Compare the objective response rate (ORR) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab.

Time frame:
Number of complete and partial responses during the study, approximately 44 months.

Results for this outcome have not been posted.

SecondaryDOR Per RECIST 1.1

Compare duration of response (DOR) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab.

Time frame:
Time from first CR or PR to PD or death from any cause, approximately 44 months.

Results for this outcome have not been posted.

SecondaryEvaluation of Adverse Events, Vital Signs, Laboratory Assessments and ECOG Performance Status

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).

Time frame:
Time from randomization to end of study, approximately 47 months.

Results for this outcome have not been posted.

Other pre-specifiedImmunological Mechanisms

To elucidate the immunological mechanisms underlying the interplay between immune activation provoked by UV1 vaccination and inhibition of tumor resistance mechanisms and peripheral immune tolerance induced by checkpoint blockade and how biological factors affect the efficacy of the combination therapy. This will be evaluated by change in immune- and tumor-related gene, cell, and protein profiles in blood over time in both treatment arms (analysis of plasma proteins, cell-free plasma DNA, and cellular genomic DNA).

Time frame:
Time from randomization to end of study to readout of primary objectives, approximately 44 months.

Results for this outcome have not been posted.

Adverse events

Collected over 44 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
UV1 Vaccination + Nivolumab and Ipilimumab22/76 (28.9%)40/76 (52.6%)76/76 (100%)
Nivolumab and Ipilimumab17/78 (21.8%)43/78 (55.1%)78/78 (100%)
Most frequent serious events
Showing 10 of 105
Most frequent serious events
EventUV1 Vaccination + Nivolumab and IpilimumabNivolumab and Ipilimumab
ColitisGastrointestinal disorders4/767/78
Immune-mediated enterocolitisGastrointestinal disorders5/765/78
PyrexiaGeneral disorders4/760/78
Immune-mediated hepatitisHepatobiliary disorders4/763/78
HepatitisHepatobiliary disorders1/764/78
DiarrhoeaGastrointestinal disorders3/762/78
PneumoniaInfections and infestations3/761/78
HypophysitisEndocrine disorders1/763/78
VomitingGastrointestinal disorders0/763/78
HeadacheNervous system disorders0/763/78
Most frequent other events
Showing 10 of 56
Most frequent other events
EventUV1 Vaccination + Nivolumab and IpilimumabNivolumab and Ipilimumab
FatigueGeneral disorders31/7633/78
rfwGastrointestinal disorders26/7621/78
DiarrhoeaGastrointestinal disorders24/7622/78
RashSkin and subcutaneous tissue disorders19/7623/78
PyrexiaGeneral disorders21/7610/78
PruritusSkin and subcutaneous tissue disorders21/7621/78
Decreased appetiteMetabolism and nutrition disorders15/7611/78
Alanine aminotransferase increasedInvestigations11/7615/78
HeadacheNervous system disorders9/7615/78
VomitingGastrointestinal disorders13/7613/78

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)UV1 Vaccination + Nivolumab and IpilimumabNivolumab and IpilimumabTotal
<=18 years000
Between 18 and 65 years405595
>=65 years382361
Sex: Female, Male
Sex: Female, Male(Participants)UV1 Vaccination + Nivolumab and IpilimumabNivolumab and IpilimumabTotal
Female252954
Male5349102
Race (NIH/OMB)
Race (NIH/OMB)(Participants)UV1 Vaccination + Nivolumab and IpilimumabNivolumab and IpilimumabTotal
American Indian or Alaska Native000
Asian112
Native Hawaiian or Other Pacific Islander000
Black or African American000
White7576151
More than one race000
Unknown or Not Reported213
Region of Enrollment
Region of Enrollment(participants)UV1 Vaccination + Nivolumab and IpilimumabNivolumab and IpilimumabTotal
Belgium171128
United States293463
Norway111627
United Kingdom211738
08

Study locations

37 sites
  • Mayo Clinic Hospital
    Phoenix, Arizona 85016-4880, United States
  • Highlands Oncology Group
    Fayetteville, Arkansas 72703, United States
  • University of California Irvine Health
    Orange, California 92868, United States
  • California Cancer Associates for Research & Excellence (CCARE
    San Marcos, California 92083, United States
  • Ridley-Tree Cancer Center
    Santa Barbara, California 93105, United States
  • Saint John's Health Center - John Wayne Cancer Institute (JWCI)
    Santa Monica, California 90404, United States
  • University of Colorado Hospital - Anschutz Cancer Pavilion
    Aurora, Colorado 80045, United States
  • Holy Cross Medical Group
    Fort Lauderdale, Florida 33308, United States
  • Sylvester Comprehensive Cancer Center
    Miami, Florida 33136-1002, United States
  • Ocala Oncology Center
    Ocala, Florida 34474, United States
  • Rush University Medical Center - Rush University Cancer Center
    Chicago, Illinois 60612-3841, United States
  • NorthShore University Research Institute
    Evanston, Illinois 60201-1718, United States
  • Oncology Specialists, S.C.
    Park Ridge, Illinois 60068, United States
  • Norton Cancer Institute
    Louisville, Kentucky 40241, United States
  • Nebraska Cancer Specialists- Midwest Cancer Center
    Papillion, Nebraska 68046-5706, United States
  • Icahn School of Medicine at Mount Sinai
    New York, New York 10029, United States
  • State University of New York (SUNY) Upstate Medical University
    New York, New York 13210, United States
  • University of Rochester
    Rochester, New York 14642-0001, United States
  • NorthShore University HealthSystem
    Greenville, South Carolina 29607, United States
  • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    Dallas, Texas 75246-2092, United States
  • Antwerp University Hospital
    Antwerp, 2650, Belgium
  • Cliniques Universitaires Saint-Luc
    Brussel, 1200, Belgium
  • Leuven University Hospital
    Leuven, 3000, Belgium
  • GZA Hospital Sint-Augustinus
    Wilrijk, 2610, Belgium
  • Sykehuset Østfold HF
    Gralum, 1714, Norway
  • Sørlandet Sykehus HF(SSHF)
    Kristiansand, 4615, Norway
  • Oslo University Hospital - The Norwegian Radium Hospital
    Oslo, 4953, Norway
  • Stavanger University Hospital
    Stavanger, 4068, Norway
  • Universitetssykehuset Nord-Norge HF
    Tromsø, 9019, Norway
  • St. Olavs Hospital HF
    Trondheim, 7030, Norway
  • Ålesund Hospital- Helse Sunnmore HF
    Ålesund, 6026, Norway
  • University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre
    Bristol, BS2 8ED, United Kingdom
  • Velindre NHS Trust
    Cardiff, CF15 7QZ, United Kingdom
  • The Royal Free London NHS Foundation Trust - The Royal Free Hospital
    London, NW3 2QG, United Kingdom
  • Royal Marsden Hospital - Institute of Cancer Research - Chelsea
    London, SM2 7LN, United Kingdom
  • Cancer Research UK Manchester Institute
    Manchester, M20 4BX, United Kingdom
  • Oxford University Hospitals NHS Trust - Churchill Hospital
    Oxford, OX3 7LE, United Kingdom
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Sep 22, 2023

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 14, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04382664
Lead sponsor
Ultimovacs ASA
Responsible party
Sponsor
First posted
May 11, 2020
Start date
May 27, 2020
Primary completion
Jan 11, 2024
Completion
Apr 10, 2024
Results posted
Jan 14, 2025
Last update
Jan 14, 2025

Study contacts

Karl Lewis
principal investigator · University of Colorado Hospital - Anschutz Cancer Pavilion

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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