Sitravatinib and Tislelizumab in Patients With Metastatic Uveal Melanoma With Liver Metastases.

Inclusion Criteria

• Patients must have histologically confirmed metastatic uveal melanoma with measurable disease not eligible for curative therapy.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral computed tomography scan, magnetic resonance imaging, or calipers by clinical exam. Patients must have at least 1 biopsiable liver metastasis.
• Patients who are human leukocytes antigen (HLA)-A02:01 positive can have received one prior therapy with Tebentafusp for metastatic disease.
• Patients must be 18 years of age or older at time of study entry.
• Eastern Cooperative Oncology Group Performance Status 0-1.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations not performed according to normal practice. Patients must consent for liver metastasis biopsies donation at day 0 and day +42 since treatment initiation.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count >1.5 x 109/L (> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (>75,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with Coordinating Investigator
• Both aspartate aminotransferase and alanine aminotransferase must be 1 year ago
• Chemotherapy induced menopause with >1 year interval since last menses
• Surgical sterilization (bilateral oophorectomy or hysterectomy)
• Women 1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• For both male and female patients/partners: Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 6 months after the last dose of tislelizumab and/or sitravatinib. A sterile male is defined as:
• One for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility.
• Males with known "low sperm counts" (consistent with "sub-fertility") are not to be considered sterile for purposes of this study.
• Patient is willing and able to comply with the protocol procedures for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Must have a life expectancy of at least 12 weeks
• Subjects must be able to swallow and retain oral medications and be without clinically significant gastrointestinal illnesses that would preclude absorption of Sitravatinib.
• Adequately controlled blood pressure:

Systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mmHg in the presence or absence of a stable regimen of antihypertensive therapy.

Exclusion Criteria

• Patients with concomitant malignancy other than non-melanoma skin cancer, or superficial bladder cancer controlled with local treatment.
• Previous treatment with targeted therapies and/or anti-angiogenic agents such as VEGFR, mitogen activated protein kinase (MAPK) - extracellular signal-regulated kinase (ERK), BRAF, ERK inhibitors, with the excepti