Phase II, Open-Label Study of Preliminary Efficacy of Sitravatinib in Combination With Tislelizumab in Patients With Metastatic Uveal Melanoma With Liver Metastases.
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Grupo Español Multidisciplinar de Melanoma
- Enrollment
- 16
- Locations
- 4
- Primary Endpoint
- Objective Response rate (ORR)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 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-
- •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:
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, 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.
- •Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- •Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Coordinating Investigator.
Arms & Interventions
Experimental arm
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.
Intervention: Tislelizumab (Drug)
Experimental arm
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.
Intervention: Sitravatinib Malate (Drug)
Outcomes
Primary Outcomes
Objective Response rate (ORR)
Time Frame: Throughout the study period, approximately 1 year per patient
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.
Secondary Outcomes
- 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)