Adds liver radiotherapy to standard treatment for uveal melanoma spread to liver

Who can take part

• written informed consent
• 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
• Will and ability to comply with the protocol
• Age ≥18 years
• Female and male
• PS (ECOG) 0 or 1
• Histologically or cytologically confirmed metastatic uveal melanoma HLA-A*02:01 positive
• Presence of liver metastases, at least one measurable lesion (RECIST v 1.1), with largest liver metastasis ≤ 8 cm
• 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
• Woman of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drugs
• 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

Who cannot take part

• Previous systemic therapy for metastatic uveal melanoma
• Previous liver directed therapy
• Morning cortisol < lower limit of normal (unless the participant has asymptomatic adrenal insufficiency and is receiving stable replacement doses)
• 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
• 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
• Hypersensitivity to the active substance or to any of the excipients
• 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
• 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
• 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
• Largest liver metastasis > 8 cm
• Symptomatic central nervous system metastases