Melanoma
Conditions
Brief summary
In 2014, an estimated 7,000 patients were diagnosed of melanoma in China. It is growing at an annual rate of 3%-5% and approximately 20,000 new cases are reported each year recently.To date, CFDA only approved dacarbazine as first line chemotherapy and anti-PD-1 antibody monotherapy as second line. There is no standard of care after chemotherapy and anti-PD-1.
Detailed description
This is an open-label, randomized, single center phase 2 study evaluating the efficacy and safety of sitravatinib in combination with tislelizumab for Chinese patients with unresectable or metastatic melanoma after disease progression from prior anti-PD-1 antibody and chemotherapy. The first 20 patients will be randomized in a 1:1 ratio to receive either sitravatinib plus tislelizumab (Arm A) or sitravatinb monotherapy (Arm B). After the completion of initial 20 patients, additional patients will be recruited until 24 efficacy evaluable patients achieved in Arm A
Interventions
DRUGsitravatinib
sitravatinib 100mg QD PO
DRUGtislelizumab
tislelizumab 200mg Q3W IV
Sponsors
Peking University Cancer Hospital & Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the Schedule of Assessments 2. Age ≥ 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place) 3. Disease progression from prior chemotherapy and anti-PD-(L)1 therapy (including sequential or combined therapy, regardless of the order) 4. No antiPD-1/PD-L1 related toxicity during the prior treatment 5. Have not received other immunotherapy, including but not limited to anti-OX40, anti-TIGIT and anti-CD137, etc. 6. BRAF wild-type patients, or patients with BRAF mutations who are not suitable or refused to receive targeted therapy with BRAF inhibitors and/or MEK inhibitors 7. Have not been exposed to small molecule targeted drugs with anti-angiogenesis effect, or VEGFR TKI drugs 8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 9. Adequate hematologic and end-organ function 10. Have not received radiotherapy, endocrine therapy, molecular targeted therapy, or surgery within 2 weeks before the start of the study, and have recovered from the acute toxicity of the previous treatment 11. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drugs and have a negative serum pregnancy test ≤ 7 days of first dose of study drugs
Exclusion criteria
1. Ocular melanoma 2. known NRAS mutations 3. Active leptomeningeal disease or brain metastases that are not well controlled. 4. History of active autoimmune disease 5. Any active malignancy ≤ 2 years 6. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before first dose of study drugs 7. History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases, including pulmonary fibrosis, acute lung diseases, etc. 8. Severe chronic or active infections (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal or antiviral therapy, within 14 days prior to first dose of study drugs 9. Known history of HIV infection 10. Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drugs 11. Prior allogeneic stem cell transplantation or organ transplantation 12. Hypersensitivity to tislelizumab or sitravatinib, to any ingredient in the formulation, or to any component of the container 13. Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic INR monitoring within 6 months before first dose of study drugs 14. Concurrent participation in another therapeutic clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) in Arm A | 12 months | defined as the proportion of participants with partial response or complete response as determined by the investigators based on RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) in Arm B | 12 months | defined as the proportion of participants with partial response or complete response as determined by the investigators based on RECIST v1.1 |
| Disease control rate (DCR) in Arm A and B | 12 months | defined as the proportion of participants whose best overall response (BOR) is complete response, partial response or stable disease as determined by investigators based on RECIST v1.1 |
| Progression-free survival (PFS) in Arm A and B | 12 months | defined as the time from randomization to the first occurrence of disease progression as determined by the investigator based on RECIST v1.1, or death from any cause, whichever occurs first |
| Incidence of Treatment-Emergent Adverse Events | 12 months | According to National Cancer Institute Common Terminology Criteria for Adverse Events V5.0(CTCAE V5.0) |
Countries
China
Contacts
Primary ContactJun Guo, MD
Backup ContactChuanliang Cui, MD
Outcome results
None listed