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

NCT05542342 | Completed Phase 2

• 2 other identifiers: GEM21012021-002474-99
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

SITISVEAL stablish the hypothesis that treatment with Tislelizumab + Sitravatinib will increase the Objective Response Rate in patients with Metastatic Uveal Melanoma (mUM) with liver metastases, compared with the current standard of care. This is a non-randomized, single arm, multicenter, phase II study of Sitravatinib in combination with Tislelizumab in subjects with metastatic uveal melanoma and liver metastases. After informed consent is obtained, subjects will enter in the Screening phase to assess eligibility criteria and perform a mandatory tumor biopsy. Upon meeting criteria, eligible subjects will be entered into the Treatment phase. Patients will receive Sitravatinib 100 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks until progression of disease, unacceptable toxicity, death, or consent withdrawal, whichever occurs first. Treatment may be continued after progression according to physician criteria (with previous consultation with Coordinating investigator) until patients no longer receive clinical benefit.

Conditions

Uveal Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective Response rate (ORR)

  ORR is defined as the proportion of patients with at least one visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later according to Response evaluation criteria in solid tumors (RECIST) version 1.1 criteria.

  Throughout the study period, approximately 1 year per patient

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  Throughout the study period, approximately 1 year per patient

• Overall survival (OS)

  Throughout the study period, approximately 1 year per patient

• Frequency of Adverse Reactions

  Throughout the study period, approximately 1 year per patient

Study Arms (1)

Experimental arm

EXPERIMENTAL

Patients will receive Sitravatinib 100 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks until progression of disease, unacceptable toxicity, death, or consent withdrawal, whichever occurs first. Treatment may be continued after progression according to physician criteria (with previous consultation with Coordinating investigator) until patients no longer receive clinical benefit.

Drug: Tislelizumab; Drug: Sitravatinib Malate

Interventions

Tislelizumab DRUG

200 mg IV once every 3 weeks

Experimental arm

Sitravatinib Malate DRUG

100 mg orally once daily

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 CT scan, MRI, or calipers by clinical exam. Patients must have at least 1 biopsiable liver metastasis.
• Patients who are human leucocites 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 (ECOG) 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:
• a) Haemoglobin ≥9.0 g/dL b) Absolute neutrophil count (ANC) \>1.5 x 109/L (\> 1500 per mm3) c) Platelet count ≥ 100 x 109/L (\>75,000 per mm3) d) 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 e) Both aspartate aminotrnsferase (AST) and alanine aminotransferase (ALT) must be \< 5 x ULN.
• f) Creatinine clearance ⩾40 ml/min calculated by Cockcroft-Gault or another validated method g) Urine protein:creatinine ratio (UPC) ≤1 or ≤2+ proteinuria on 2 consecutive dipsticks taken no less than 1 week apart h) Subjects with 2+ proteinuria on dipstick must also have UPC \< 0.5 on 2 consecutive samples.
• Females of childbearing potential 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, and have a negative urine or serum pregnancy test ≤ 7 days before first administration of Tislelizumab and Sitravatinib. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• a) Amenorrheic for ≥1 year in the absence of chemotherapy and/or hormonal treatments b) Luteinizing hormone (LH) and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range c) Radiation induced oophorectomy with last menses \>1 year ago d) Chemotherapy induced menopause with \>1 year interval since last menses e) Surgical sterilization (bilateral oophorectomy or hysterectomy) f) Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) g) Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>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.

You may not qualify if:

• 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, MEK, BRAF, ERK inhibitors, with the exception of Tebentafusp.
• Previous treatment with immune checkpoint inhibitors, either anti-PD1/PD-L1 (Including Tislelizumab), anti-CTLA-4, or other treatments.
• Presence of brain or leptomeningeal involvement unless previously treated, off steroids at least 2 weeks, and considered stable. Patients with untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging \[RECIST\]) obtained during the screening period or identified prior to signing the ICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10mg/day of prednisone or its equivalent and anticonvulsants, for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
• Patients weighing \<30kg will be excluded from enrollment.
• Participation in another clinical study with an investigational product during the last 4 weeks.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤28 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or Pharmacokinetic properties of an agent, a longer wash-out period will be required, as agreed by Sponsor designated Coordinating Investigator and Principal Investigator.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Coordinating Investigator.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with Tislelizumab may be included only after consultation with the Coordinating Investigator.
• Known toxicity on prior checkpoint inhibitor treatment:
• I) Grade ≥ 3 immune-related adverse event (AE) related to checkpoint inhibitors.
• CNS or ocular AE of any grade related to checkpoint inhibitors. Note: Patients with a prior endocrine AE are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Any concurrent chemotherapy, investigational medicinal product (IMP), biologic, or hormonal therapy for cancer treatment different to Sitravatinib and/or Tislelizumab. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.

Sponsors & Collaborators

• Grupo Español Multidisciplinar de Melanoma: lead
• Mirati Therapeutics Inc.: collaborator
• BeiGene: collaborator

Study Sites (4)

Hospital Universitario Virgen de la Macarena

Seville, Andalusia, 41009, Spain

Location

Institut Catala Oncologia (ICO) L´Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario la Paz

Madrid, Madrid, 28046, Spain

Location

Hospital General Universitario de Valencia

Valencia, Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Uveal Melanoma

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Officials

• Josep Maria Piulats, M.D. Ph.D.

  ICO L´Hospitalet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 15, 2022
• Study Start: September 23, 2022
• Primary Completion: December 31, 2023
• Study Completion: May 6, 2025
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)