Sitravatinib With or Without Tislelizumab in Patients With Unresectable or Metastatic Melanoma

A Phase II Study Exploring the Safety, Tolerability and Preliminary Anti-tumor Activity of Sitravatinib With or Without Tislelizumab in Patients With Unresectable or Metastatic Melanoma

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Drug: sitravatinib; Drug: tislelizumab

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

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: tislelizumab+sitravatinib; Patients will receive sitravatinib 100 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent.	Drug: sitravatinib; sitravatinib 100mg QD PO; Drug: tislelizumab; tislelizumab 200mg Q3W IV
Experimental: Arm B: sitravatinib; Patients will receive sitravatinib 100 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent.	Drug: sitravatinib; sitravatinib 100mg QD PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) in Arm A	defined as the proportion of participants with partial response or complete response as determined by the investigators based on RECIST v1.1	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) in Arm B	defined as the proportion of participants with partial response or complete response as determined by the investigators based on RECIST v1.1	12 months
Disease control rate (DCR) in Arm A and B	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	12 months
Progression-free survival (PFS) in Arm A and B	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	12 months
Incidence of Treatment-Emergent Adverse Events	According to National Cancer Institute Common Terminology Criteria for Adverse Events V5.0(CTCAE V5.0)	12 months

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: October 22, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): November 4, 2021
• Last Update Submitted That Met QC Criteria: November 2, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: BGB-900-2002-IIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No