Safety of UV1 Vaccination in Combination With Ipilimumab in Patients With Unresectable or Metastatic Malignant Melanoma

This study, with 20 patients participating, will examine the safety and tolerability for the ipilimumab/UV1 combination in patients with unresectable or metastatic malignant melanoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Melanoma
• Intervention / Treatment: Drug: Ipilimumab; Biological: UV1 vaccine; Biological: GM-CSF

Detailed Description

This is a phase I/IIa, national, open label, single arm, interventional study examining safety and tolerability for the ipilimumab/UV1 combination in patients with unresectable or metastatic malignant melanoma. Patients that have signed the informed consent form will be asked to take part in the study. All patients will receive ipilimumab together with the UV1 vaccine and rranulocyte-macrophage colony-stimulating factor (GM-CSF). Ipilimumab will be given every 3rd week for a total of 4 doses. The UV1 vaccine and GM-CSF will be given before and between treatments of ipilimumab. The maximum number of UV1/GM-CSF will be 10 doses.

Immunoresponders maybe followed up every third months for 5 years after the first UV1 treatment. Follow-up is onging.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0379
    • Oslo University Hospital, Radiumhospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of unresectable or metastatic malignant melanoma, including cutaneous, ocular, mucosal and unknown primary tumour.
2. Unresectable Stage III or Stage IV melanoma (AJCC 2010)
3. Prior adjuvant melanoma therapy is permitted; any number of previous treatments for melanoma is permitted.
4. ECOG performance status of 0 or 1 (see Error! Reference source not found.).
5. Men and women ≥ 18 years of age

6. Adequate hematologic, renal and hepatic function, specifically:

   1. WBC ≥ 2500/μL
   2. Absolute neutrophil count (ANC) ≥ 1000/uL
   3. Platelets ≥ 75 x 103/μL
   4. Haemoglobin ≥ 9 g/dL
   5. Creatinine ≤ 2.5 x ULN
   6. AST/ALT ≤ 3 x ULN for patients without liver metastasis; ≤ 5 x ULN for patients with liver metastasis
   7. Total bilirubin ≤ 3 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
7. Women of childbearing potential and men must be using an acceptable method as described in the protocol to prevent pregnancy.
8. Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.

Exclusion Criteria:

1. History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (e.g. Guillain-Barre syndrome). Patients with vitiligo are not excluded.
2. MRI detected active brain metastasis witch require other therapies such as surgery and/or radiation therapy. Patients already treated for their brain metastasis, surgery or radiation therapy, and have had stable disease for more than two month and NOT requiring steroids may however be included in this study.
3. Uncontrolled infectious diseases - requires negative tests for clinically suspected human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV).
4. History of or current immunodeficiency disease, splenectomy or splenic irradiation
5. Prior allogeneic stem cell transplantation
6. Pregnancy
7. Women who are breastfeeding
8. Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of Adverse Events, such as a condition associated with frequent diarrhoea
9. History of allergic reaction to parenteral administered recombinant protein product
10. History of another malignancy that in the opinion of the investigator may compromise the outcome of the study
11. Any reason why, in the opinion of the investigator, the patient should not participate.
12. Known serious reactions or hypersensitivity to any components of the UV1 vaccine or similar peptide based vaccines
13. Known hypersensitivity to GM-CSF
14. Known hypersensitivity to any of the excipients of the investigational products
15. Concomitant use of antithrombotic agents with the exception of platelet inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ipilimumab & UV1 vaccine & GM-CSF; Ipilimumab (3 mg/kg) every 3rd week for a total of 4 doses. GM-CSF (75 μg) followed by UV1 vaccine (300 μg) will be injected intradermally in the lower abdomen before and between treatments of ipilimumab and thereafter every 4th week up to 28 weeks, and thereafter at week 36 and 48.	Drug: Ipilimumab; Other Names: Yervoy; Biological: UV1 vaccine; Other Names: UV1; Biological: GM-CSF; Other Names: Leukine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability profile. Frequency/ severity of adverse and serious adverse events. Biochemistry and hematology results, vital signs and ECOG	Frequency and severity of adverse events and serious adverse events. Biochemistry and hematology results, vital signs and ECOG performance status will be assessed.	Up to 53 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological response. Number of T-cell responses including time to T-cell response, level of response and duration of response.	Number of T-cell responses including time to T-cell response, level of response and duration of response.	Up to 53 weeks
Treatment response. Tumour response evaluated by CT scan every 12th week.	Tumour response evaluated by CT scan every 12th week.	Up to 48 weeks
Health Related Quality of Life (HRQL)	HRQL measured by use of patient questionnaire EORTC QLQ-C30	Up to 53 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explore potential biomarkers for efficacy and safety of the ipilimumab/UV1 combination	Exploratory biomarker analysis.	Up to 48 weeks

Collaborators and Investigators

• Sponsor: Ultimovacs ASA
• Collaborators: Oslo University Hospital
• Investigators: Principal Investigator: Tormod Guren, MD PhD, Oslo University Hospital

Publications and helpful links

General Publications

• Ellingsen EB, Bounova G, Kerzeli I, Anzar I, Simnica D, Aamdal E, Guren T, Clancy T, Mezheyeuski A, Inderberg EM, Mangsbo SM, Binder M, Hovig E, Gaudernack G. Characterization of the T cell receptor repertoire and melanoma tumor microenvironment upon combined treatment with ipilimumab and hTERT vaccination. J Transl Med. 2022 Sep 11;20(1):419. doi: 10.1186/s12967-022-03624-z.
• Aamdal E, Inderberg EM, Ellingsen EB, Rasch W, Brunsvig PF, Aamdal S, Heintz KM, Vodak D, Nakken S, Hovig E, Nyakas M, Guren TK, Gaudernack G. Combining a Universal Telomerase Based Cancer Vaccine With Ipilimumab in Patients With Metastatic Melanoma - Five-Year Follow Up of a Phase I/IIa Trial. Front Immunol. 2021 May 11;12:663865. doi: 10.3389/fimmu.2021.663865. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2015
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: September 12, 2014
• First Submitted That Met QC Criteria: October 24, 2014
• First Posted (Estimate): October 27, 2014

Study Record Updates

• Last Update Posted (Actual): May 17, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: UV1/hTERT-MM; 2013-005582-39 (EudraCT Number)