UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma

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)

UV1 is a therapeutic cancer vaccine that has been explored in prostate, lung cancer, in combination with ipilimumab in malignant melanoma and in combination with pembrolizumab in metastatic melanoma. This study will explore the Efficacy and Safety of UV1 administered with GM-CSF in combination with nivolumab and ipilimumab.

Study Overview

• Status: Completed
• Conditions: Malignant Melanoma
• Intervention / Treatment: Biological: UV1; Biological: Sargramostim; Biological: Ipilimumab; Biological: Nivolumab

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.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Øivind Foss; Phone Number: 0047 970 08 357; Email: oivind.foss@ultimovacs.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UV1 vaccination + nivolumab and ipilimumab	Biological: UV1; UV1 vaccine (300 μg) will be injected intradermally.; Biological: Sargramostim; Sargramostim (75 μg) is used as a vaccine adjuvant.; Other Names: Leukine; Biological: Ipilimumab; Ipilimumab is dosed according to label.; Other Names: Yervoy; Biological: Nivolumab; Nivolumab is dosed according to label.; Other Names: Opdivo
Active Comparator: Nivolumab and ipilimumab; nivolumab and ipilimumab	Biological: Ipilimumab; Ipilimumab is dosed according to label.; Other Names: Yervoy; Biological: Nivolumab; Nivolumab is dosed according to label.; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Compare progression free survival (PFS) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab	Time from randomization to progressive disease (PD) or death from any cause, estimated up to 27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Compare Overall Survival of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab .	Time from randomization to death from any cause /follow-up until 70 PFS, estimated up to 51 months
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 from first ORR or death from any cause, estimated up to 27 months.
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 from first CR or PR to PD or death from any cause, estimated up to 27 months.
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 from randomization to end of study, estimated up to 27 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 from randomization to end of study, estimated up to 27 months

Collaborators and Investigators

• Sponsor: Ultimovacs ASA
• Investigators: Principal Investigator: Karl Lewis, University of Colorado Hospital - Anschutz Cancer Pavilion

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): January 11, 2024
• Study Completion (Actual): April 10, 2024

Study Registration Dates

• First Submitted: April 27, 2020
• First Submitted That Met QC Criteria: May 7, 2020
• First Posted (Actual): May 11, 2020

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab; Sargramostim
• Other Study ID Numbers: UV1-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No