UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma

• ClinicalTrials.gov Identifier: NCT04382664
• Recruitment Status: Completed
• First Posted: May 11, 2020
• Last Update Posted: April 18, 2024
• Sponsor: Ultimovacs ASA
• Information provided by (Responsible Party): Ultimovacs ASA

Tracking Information

• First Submitted Date: April 27, 2020
• First Posted Date: May 11, 2020
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: June 15, 2020
• Actual Primary Completion Date: January 11, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2020)

PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: Time from randomization to progressive disease (PD) or death from any cause, estimated up to 27 months ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 15, 2021)

• Overall Survival [ Time Frame: Time from randomization to death from any cause /follow-up until 70 PFS, estimated up to 51 months ]
  Compare Overall Survival of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab .
• ORR per RECIST 1.1 [ Time Frame: Time from first ORR or death from any cause, estimated up to 27 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 Frame: Time from first CR or PR to PD or death from any cause, estimated up to 27 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 Frame: Time from randomization to end of study, estimated up to 27 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).

Original Secondary Outcome Measures (submitted: May 7, 2020)

• Overall Survival [ Time Frame: Time from randomization to death from any cause /follow-up until 70 PFS, estimated up to 27 months ]
  Compare Overall Survival of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab .
• ORR per RECIST 1.1 [ Time Frame: Time from first ORR or death from any cause, estimated up to 27 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 Frame: Time from first CR or PR to PD or death from any cause, estimated up to 27 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 Frame: Time from randomization to end of study, estimated up to 27 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).

Current Other Pre-specified Outcome Measures (submitted: May 7, 2020)

Immunological mechanisms [ Time Frame: Time from randomization to end of study, estimated up to 27 months ]

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).

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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)
• Brief Summary: 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Malignant Melanoma

Intervention

• Biological: UV1
  UV1 vaccine (300 μg) will be injected intradermally.
• Biological: Sargramostim
  Sargramostim (75 μg) is used as a vaccine adjuvant.
  Other Name: Leukine
• Biological: Ipilimumab
  Ipilimumab is dosed according to label.
  Other Name: Yervoy
• Biological: Nivolumab
  Nivolumab is dosed according to label.
  Other Name: Opdivo

Study Arms

• Experimental: UV1 vaccination + nivolumab and ipilimumab
  UV1 vaccination + nivolumab and ipilimumab
  Interventions:

  • Biological: UV1
  • Biological: Sargramostim
  • Biological: Ipilimumab
  • Biological: Nivolumab
• Active Comparator: Nivolumab and ipilimumab
  nivolumab and ipilimumab
  Interventions:

  • Biological: Ipilimumab
  • Biological: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 20, 2023): 156
• Original Estimated Enrollment (submitted: May 7, 2020): 154
• Actual Study Completion Date: April 10, 2024
• Actual Primary Completion Date: January 11, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Norway, United Kingdom, United States

Administrative Information

• NCT Number: NCT04382664
• Other Study ID Numbers: UV1-202
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ultimovacs ASA
• Original Responsible Party: Same as current
• Current Study Sponsor: Ultimovacs ASA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Karl Lewis; University of Colorado Hospital - Anschutz Cancer Pavilion

• PRS Account: Ultimovacs ASA
• Verification Date: April 2024