Neoadjuvant Immunotherapy for Patients With High-risk Eye Melanoma

Neoadjuvant Ipilimumab and Nivolumab for Patients With High-risk Uveal Melanoma

The goal of this clinical trial is to investigate the safety and feasibility of neoadjuvant immunotherapy for patients with high-risk uveal melanoma. The main question is:

- Is neoadjuvant treatment with nivolumab and ipilimumab safe and feasible for patientt with high-riks uveal melanoma? In addition pathological response, distant metastases-free survival, overall survival and immunological changes in the tumor microenviroenment after therapy will be assesed.

Study Overview

• Status: Not yet recruiting
• Conditions: Uveal Melanoma
• Intervention / Treatment: Drug: Nivolumab & Ipilimumab

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Inge Marie Svane, Professor, MD; Phone Number: 004538683868; Email: inge.marie.svane@regionh.dk
• Study Contact Backup: Name: Tine Juul Monberg, MD, PhD; Phone Number: 004538683868; Email: tine.monberg@regionh.dk

Study Locations

• Denmark
  • Herlev
    • Herlev, Herlev, Denmark, 2730
      • National Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital
      • Contact: Tine Juul Monberg, MD, PhD; Phone Number: 004538683868; Email: tine.monberg@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 ≤ 80
• The patient is able to read and understand Danish.
• Primary, localized and treatment-naive uveal melanoma planned for enucleation (high risk/T3-T4) and available for transvitreal biopsies. The initial diagnosis of uveal melanoma is based on ophthalmologic and clinical findings.
• ECOG performance status of 0 or 1 (appendix 2)
• The patient meets the following haematological and biochemical criteria at time of screening: a) AST and ALT ≤2,5 X ULN, b) Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total bilirubin level > 1,5 ULN, c) Serum creatinine ≤1,5 X ULN, d) ANC (Absolute Neutrophil Count) ≥1,000/mcL, e) Platelets ≥ 75,000 /mcL, f) Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
• Signed statement of consent after receiving oral and written study information
• Willingness to participate in the planned treatment and follow-up schedule
• For women of childbearing potential (WOCBP) a negative serum pregnancy test at time of screening and the use of highly effective contraception is required. This applies from screening and until 6 months after treatment.

The following is considered highly effective methods of contraception: 1. Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal or transdermal), 2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 3. Intrauterine device (IUD) 4. intrauterine hormone-releasing system (IUS) 5. Bilateral tubal occlusion, 6. Vasectomised partner provided that the vasectomy is confirmed successful, 7. Sexual abstinence defined as refraining from heterosexual intercourse. WOCBP must also agree to refrain from egg donation, storage, or banking during these same time periods.

- Men with female partner of childbearing potential must: 1. Use a condom during sexual intercourse from screening and until 6 months after treatment. 2.

Ensure that their partner uses a highly effective method of contraception (as described above) 3. Agree to refrain from sperm donation, storage, or banking

Exclusion criteria

• A history of prior malignancies. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 2 years after treatment. Subjects with curatively treated ductal carcinoma in situ (DCIS or LCIS) breast cancer for which they are taking hormonal therapy is acceptable. Resectable squamous or basal cell carcinoma of the skin is acceptable.
• Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 3 weeks prior to screening
• The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)
• The patient is pregnant or breastfeeding
• The patient has an active infection requiring systemic therapy
• Significant medical disorder according to investigator; e.g severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus.
• Concurrent treatment with other experimental drugs
• Any significant active autoimmune disease
• Severe allergy or anaphylactic reactions earlier in life
• Known hypersensitivity to one of the active drugs or one or more of the excipients.

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: Neoadjuvant nivolumab + ipilimumab	Drug: Nivolumab & Ipilimumab; Nivolumab 3 mg/kg Ipilimumab 1 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients experiencing CTCAE grade ≥ 3 AEs and the occurrence of any treatment related adverse event (AEs)	Safety is evaluated by the Common Terminology Criteria (CTCAE) for Adverse Events version 6.0 and include the number of patients experiencing CTCAE grade ≥ 3 AEs and the occurrence of any treatment related adverse event (AEs) until 6 months post treatment.	Until 6 months post treatment
Proportion of patients who complete the treatment regimen	Feasibility is evaluated as the proportion of patients who complete the treatment regimen defined as receiving at least one dose of both nivolumab and ipilimumab, followed by enucleation	Until 6 months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological response rate	The fraction of pathological responses according to standard evaluation criteria	through study completion, an average of 3 years
Objective response	Size and extend of the tumor at baseline and after the second dose of nivolumab and ipilimumab.	through study completion, an average of 3 years
Distant metastases free survival (DMFS)	DMFS will be evaluated as the time from treatment initiation to the development of any distant metastasis or death.	Until 6 months post treatment
Overall survival (OS)	OS will be evaluated as the time from treatment initiation to death from any cause	Until 6 months post treatment

Collaborators and Investigators

• Sponsor: Inge Marie Svane

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Immunotherapy; Ipilimumab; Neoadjuvant therapy; High-risk uveal melanoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Uveal Diseases; Melanoma; Uveal Neoplasms; Uveal Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Ipilimumab
• Other Study ID Numbers: MM2530; 2025-524526-18-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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