Hepatic radiotherapy added to standard of care for the treatment of HLA A*02:01 positive Metastatic Uveal Melanoma patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Oct 2025 → ongoing

Decision date (initial)

2025-07-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Immunocore Limited

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To prolong progression free survival (PFS) with the addition of a liver directed therapy to tebentafusp

Secondary objectives 7

1. to increase the clinical benefit
2. to prolong overall survival (OS)
3. to extend the time patients stay on treatment
4. to delay the time to subsequent treatment initiation
5. to investigate the markers of immune response and resistance during treatment
6. to explore the ctDNA modifications during treatment and the correlation with the clinical efficacy of the combination treatment
7. to evaluate the tolerability of combination treatment

Conditions and MedDRA coding

metastatic uveal melanoma HLA A*02:01 positive

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. written informed consent
2. Age ≥18 years
3. Female and male
4. PS (ECOG) 0 or 1
5. Histologically or cytologically confirmed metastatic uveal melanoma HLA-A*02:01 positive
6. Presence of liver metastases, at least one measurable lesion (RECIST v 1.1), with largest liver metastasis ≤ 8 cm
7. Adequate bone marrow, renal and liver functions: absolute neutrophil count > 1.0 x 109/L; absolute lymphocyte count > 0.5 x 109/L; platelet count > 100 x 109/L;hemoglobin > 8 g/dl;serum creatinine < 1.5 x upper limit of normal (ULN) and/or creatinine clearance > 50 ml/min;total bilirubin < 1.5 x ULN (with the exception of patients with Gilbert Syndrome who will be excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN); alanine aminotransferase < 3.0 x ULN; aspartate aminotransferase < 3.0 x ULN
8. Woman of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drugs
9. Male subjects with female partners of childbearing potential must be willing to use adequate contraception as outlined in Section 8.3 – of the protocol, starting with the first dose of study therapy through at least 1 weeks after the last dose of treatment
10. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 8.3, for the course of the study starting with the first dose of study therapy through at least 1 weeks after the last dose of treatment
11. Will and ability to comply with the protocol

Exclusion criteria 11

1. Previous systemic therapy for metastatic uveal melanoma
2. other serious or uncontrolled medical disorder, active infection, physical exam or laboratory findings, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject’s ability to comply with the study requirements
3. Previous liver directed therapy
4. Largest liver metastasis > 8 cm
5. Symptomatic central nervous system metastases
6. Participants with clinically significant cardiac disease or impaired cardiac function, including any of the following: - Congestive heart failure (New York Heart Association Class ≥ 3). - Uncontrolled hypertension (consistent findings of systolic blood pressure > 160 mmHg or diastolic > 110 mmHg). - History of ventricular arrhythmia currently requiring medical treatment. - Uncontrolled atrial fibrillation. - Electrocardiogram (ECG) QT interval corrected > 470 msec during screening obtained on triplicate ECGs or known history of congenital prolonged QT syndrome. - Acute myocardial infarction or unstable angina pectoris ≤ 6 months prior to screening
7. Morning cortisol < lower limit of normal (unless the participant has asymptomatic adrenal insufficiency and is receiving stable replacement doses)
8. Participants with active autoimmune disease requiring immunosuppressive treatment, including inflammatory bowel disease (ulcerative colitis or Crohn’s disease), within2 years of screening. The following exceptions are permitted: - Vitiligo - Alopecia - Managed hypothyroidism (on stable replacement doses) - Asymptomatic adrenal insufficiency (on stable replacement doses) - Psoriasis - Resolved childhood asthma/atopy - Well-controlled asthma - Type I diabetes mellitus
9. Participants who received systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of the planned first dose of study intervention. The following exceptions are permitted: - Treatment for well-controlled and asymptomatic adrenal insufficiency, but replacement dosing is limited to prednisone ≤ 12 mg daily or the equivalent. - Local steroid therapies (eg, optic, ophthalmic, intra-articular, or inhaled medications). - Premedication for allergy to contrast reagent. - Steroids for management of CNS metastases > 14 days prior to the planned first dose of study intervention. - To treat asthma or chronic obstructive pulmonary disease exacerbations > 14 days prior to the planned first dose of study intervention (only short-term oral or IV use in doses>12 mg/day prednisone equivalent). - For inhalation in the management of asthma or chronic obstructive pulmonary disease. - Any premedications required per protocol
10. Previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) or active malignancy requiring intervention
11. Hypersensitivity to the active substance or to any of the excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the progression-free survival, which will be calculated from the day of treatment initiation to the progression. The PFS rate at 6 months will be evaluated

Secondary endpoints 8

1. disease control rate at first tumor assessment
2. objective response rate
3. overall survival
4. treatment duration
5. time to subsequent treatment initiation
6. safety
7. evaluation of patients’ circulating immune profile and inflammatory microenvironment of uveal melanoma and correlation with PFS
8. analysis of ctDNA and correlation with PFS and OS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Ernesto Rossi

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Ernesto Rossi

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications