Clinical Trials /

UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma

NCT04382664

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: UV1-202
  • NCT ID: NCT04382664

Conditions

  • Malignant Melanoma

Interventions

DrugSynonymsArms
UV1UV1 vaccination + nivolumab and ipilimumab
SargramostimLeukineUV1 vaccination + nivolumab and ipilimumab
IpilimumabYervoyNivolumab and ipilimumab
NivolumabOpdivoNivolumab and ipilimumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
UV1 vaccination + nivolumab and ipilimumabExperimentalUV1 vaccination + nivolumab and ipilimumab
  • UV1
  • Sargramostim
  • Ipilimumab
  • Nivolumab
Nivolumab and ipilimumabActive Comparatornivolumab and ipilimumab
  • Ipilimumab
  • Nivolumab

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. Serum creatinine ≤1.5 x upper limit of normal (ULN) Hepatic

               5. Serum 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Compare progression free survival (PFS) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:Time from randomization to death from any cause /follow-up until 70 PFS, estimated up to 27 months
Safety Issue:
Description:Compare Overall Survival of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab .
Measure:ORR per RECIST 1.1
Time Frame:Time from first ORR or death from any cause, estimated up to 27 months.
Safety Issue:
Description:Compare the objective response rate (ORR) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab.
Measure: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.
Safety Issue:
Description:Compare duration of response (DOR) of UV1 vaccination in combination with nivolumab and ipilimumab to that of nivolumab and ipilimumab.
Measure: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
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ultimovacs ASA

Last Updated

May 27, 2020