Description:
The study will evaluate the clinical activity of sitravatinib in combination with nivolumab
in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant
setting prior to nephrectomy.
Title
- Brief Title: Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma
- Official Title: A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients Undergoing Nephrectomy for Locally-Advanced Clear Cell Renal Cell Carcinoma
Clinical Trial IDs
- ORG STUDY ID:
516-002
- NCT ID:
NCT03680521
Conditions
- Clear Cell Renal Cell Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Sitravatinib | | Sitravatinib and nivolumab |
Nivolumab | | Sitravatinib and nivolumab |
Purpose
The study will evaluate the clinical activity of sitravatinib in combination with nivolumab
in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant
setting prior to nephrectomy.
Detailed Description
Sitravatinib is a receptor tyrosine kinase inhibitor (TKI) that targets multiple closely
related receptor tyrosine kinase pathways including VEGFR, PDGFR, c-KIT, MET, and the TAM
family of receptors (TYRO3, AXL, and MER). Nivolumab is a monoclonal antibody directed
against PD-1 and blocks the interaction between PD-1 and its ligands, thereby releasing
PD-1-mediated inhibition of T-cell proliferation (including cytotoxic CD8+ T-cells) and
cytokine production. Together, sitravatinib and nivolumab may cooperate to elicit greater
anti-tumor activity than either agent alone, as sitravatinib is predicted to enhance several
steps in the cancer immunity cycle that may augment the efficacy of nivolumab.
Trial Arms
Name | Type | Description | Interventions |
---|
Sitravatinib and nivolumab | Experimental | Sitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy. | |
Eligibility Criteria
Inclusion Criteria:
1. Imaging results consistent with locally-advanced RCC
2. Candidate for partial or complete nephrectomy as part of treatment plan.
3. Measurable disease per RECIST version 1.1.
4. ECOG performance status 0 or 1.
5. Adequate bone marrow and organ function.
Exclusion Criteria:
1. Prior systemic anti-tumor treatment for RCC.
2. Patients who are receiving any other investigational agents.
3. Clinical status indicating that immediate surgery (within 6 weeks) is warranted
regardless of whether neoadjuvant therapy is to be administered, as assessed by the
treating surgeon.
4. Inability to undergo baseline tumor biopsy.
5. Active or prior documented autoimmune or immunocompromising conditions.
6. Uncontrolled hypertension.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery |
Time Frame: | Baseline to date of surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | Objective response is defined as the percent of participants documented by investigator assessment to have Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions. |
Secondary Outcome Measures
Measure: | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) |
Time Frame: | Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks) |
Safety Issue: | |
Description: | TEAEs occured after the first dose of any study treatment or any preexisting condition that increased in severity after the first dose of study treatment and prior to 28 days after last dose of study drug or surgery, whichever occurred last.
TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Measure: | Blood Plasma Concentrations of Sitravatinib |
Time Frame: | Day 1 (pre-dose, and 30 minutes to 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose) |
Safety Issue: | |
Description: | |
Measure: | Time to Surgery |
Time Frame: | Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy. |
Measure: | Disease Free Survival (DFS) |
Time Frame: | Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first. |
Measure: | Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor |
Time Frame: | Baseline to date of surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | |
Measure: | Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor |
Time Frame: | Baseline to date of surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | |
Measure: | Change From Baseline in Regulatory T-cells (Tregs) in the Tumor |
Time Frame: | Baseline to date of surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | |
Measure: | Change From Baseline in CD4+ T-cells in the Tumor |
Time Frame: | Baseline to date of surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | |
Measure: | Change From Baseline in CD8+ T-cells in the Tumor |
Time Frame: | Baseline to date of surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | |
Measure: | Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor |
Time Frame: | Baseline to date of surgery (maximum time to surgery was approximately 13 weeks) |
Safety Issue: | |
Description: | |
Measure: | Change From Baseline of Selected Cytokines in Peripheral Blood |
Time Frame: | Baseline to Day 43 |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Mirati Therapeutics Inc. |
Trial Keywords
- ccRCC
- MGCD516
- Antineoplastic Agents
- Immunologic factors
- nivolumab
- Tyrosine Kinase Inhibitor
- VEGFR
- TAM RTKs
- PD-1
- PD-L1
Last Updated
May 19, 2021