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Study 516-008 is an open-label Phase 1 dose escalation/Phase 1b dose expansion study evaluating the safety and tolerability, clinical activity, and PK of sitravatinib in combination with nivolumab and ipilimumab for the treatment of ccRCC and potentially other solid tumor types.
Sitravatinib is a spectrum-selective receptor tyrosine kinase (RTK) inhibitor that inhibits several closely related RTKs including the TAM family (Tyro3/Axl/MERTK), VEGFR2, KIT, and MET.
NIVO/IPI are monoclonal antibodies (mAbs) that inhibit the immune checkpoint proteins programmed death receptor-1 (PD-1) and cytotoxic T- lymphocyte antigen-4 (CTLA-4), respectively.
The current study is designed to evaluate the triple combination of sitravatinib plus NIVO/IPI in patients with solid tumor malignancies that have shown favorable responses to NIVO/IPI combinations in previous clinical trials. Combining sitravatinib and NIVO/IPI is predicted to have complementary effects in triggering a tumor-directed immune response.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1: Dose Escalation | Experimental | Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment. |
|
| Phase 1b Dose Escalation Cohort A | Experimental | Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment |
|
| Phase 1b Dose Escalation Cohort B | Experimental | Patients with favorable-risk RCC with clear cell component for first-line treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sitravatinib | Drug | Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases |
|
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of patients experiencing treatment-emergent AEs | Characterization of AEs by incidence, severity, timing, seriousness & relationship to study treatment | Through study completion, an average of 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) in accordance with RECIST v1.1 | Frequency of patients experiencing an objective response | Through duration of study, average of 10 months |
| Duration of Response (DOR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Curtis Chin, MD | Mirati Therapeutics Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MD Anderson | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39794332 | Derived | Msaouel P, Yu K, Yuan Y, Chen J, Yan X, Karki M, Duan F, Sheth RA, Rao P, Sircar K, Shah AY, Zurita AJ, Genovese G, Li M, Yeh CC, Dang M, Han G, Chu Y, Hallin M, Olson P, Yang R, Slavin D, Der-Torossian H, Chin CD, Tannir NM, Wang L, Gao J. Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial. Nat Commun. 2025 Jan 10;16(1):578. doi: 10.1038/s41467-024-55642-8. |
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Following the identification of the recommended dose of sitravatinib in combination with NIVO/IPI Phase 1 dose escalation, two Phase 1b dose expansion cohorts will enroll patients with ccRCC based on IMDC risk. All patients receive the same treatment.
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|
| Nivolumab | Drug | Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody |
|
|
| Ipilimumab | Drug | Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody |
|
|
Time in months from date of the first documentation of objective tumor response (CR or PR) to the first documentation of objective PD or to death due to any cause in the absence of documented PD
| Through duration of study, average of 10 months |
| Progression-free Survival (PFS) | Time from date of first study treatment to first PD or death due to any cause in the absence of documented PD | Through duration of study, average of 10 months |
| ID | Term |
|---|---|
| D002292 | Carcinoma, Renal Cell |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C000611865 | sitravatinib |
| D000077594 | Nivolumab |
| D000074324 | Ipilimumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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