UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma

Malignant Melanoma Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT04382664
• Other study ID #: UV1-202
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2020
• Est. completion date: April 10, 2024

Study information

• Verified date: April 2024
• Source: Ultimovacs ASA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: April 10, 2024
• Est. primary completion date: January 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

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

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Antwerp
Belgium	Cliniques Universitaires Saint-Luc	Brussel
Belgium	Leuven University Hospital	Leuven
Belgium	GZA Hospital Sint-Augustinus	Wilrijk
Norway	Ålesund Hospital- Helse Sunnmore HF	Ålesund
Norway	Sykehuset Østfold HF	Gralum
Norway	Sørlandet Sykehus HF(SSHF)	Kristiansand
Norway	Oslo University Hospital - The Norwegian Radium Hospital	Oslo
Norway	Stavanger University Hospital	Stavanger
Norway	Universitetssykehuset Nord-Norge HF	Tromsø
Norway	St. Olavs Hospital HF	Trondheim
United Kingdom	University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Velindre NHS Trust	Cardiff
United Kingdom	Royal Marsden Hospital - Institute of Cancer Research - Chelsea	London
United Kingdom	The Royal Free London NHS Foundation Trust - The Royal Free Hospital	London
United Kingdom	Cancer Research UK Manchester Institute	Manchester
United Kingdom	Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Rush University Medical Center - Rush University Cancer Center	Chicago	Illinois
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	NorthShore University Research Institute	Evanston	Illinois
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Holy Cross Medical Group	Fort Lauderdale	Florida
United States	NorthShore University HealthSystem	Greenville	South Carolina
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	State University of New York (SUNY) Upstate Medical University	New York	New York
United States	Ocala Oncology Center	Ocala	Florida
United States	University of California Irvine Health	Orange	California
United States	Nebraska Cancer Specialists- Midwest Cancer Center	Papillion	Nebraska
United States	Oncology Specialists, S.C.	Park Ridge	Illinois
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	University of Rochester	Rochester	New York
United States	California Cancer Associates for Research & Excellence (CCARE	San Marcos	California
United States	Ridley-Tree Cancer Center	Santa Barbara	California
United States	Saint John's Health Center - John Wayne Cancer Institute (JWCI)	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Ultimovacs ASA

Countries where clinical trial is conducted

United States,  Belgium,  Norway,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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.
Secondary	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.
Secondary	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