Clear-Cell Renal Cell CarcinomaPhase 1NCT04518046
Study of Sitravatinib, Nivolumab and Ipilimumab in Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies
A Phase 1 study testing Sitravatinib, Nivolumab and Ipilimumab in people with Clear-Cell Renal Cell Carcinoma, run by Mirati Therapeutics Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clear-Cell Renal Cell Carcinoma
- What is being tested?
- Sitravatinib, Nivolumab and Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Aug 2020to 30 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of Clear-Cell Renal Cell Carcinoma (for initial cohorts under consideration)
- No prior treatment with systemic therapy (for initial cohorts under consideration)
- Adequate bone marrow and organ function
Who cannot join
- Known or suspected presence of other cancer
- Brain metastases (for initial cohorts under consideration)
- Carcinomatous meningitis
- Immunocompromising conditions
- Impaired heart function
- Active or prior documented autoimmune disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1/1b Study of Sitravatinib in Combination With Nivolumab and Ipilimumab in Patients With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies
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.
Read the detailed description
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.
- Conditions
- Clear-Cell Renal Cell Carcinoma
- Being tested
- Sitravatinib, Nivolumab, Ipilimumab
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitravatinibDrug
Also called MGCD516
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
NivolumabDrug
Also called OPDIVO
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
IpilimumabDrug
Also called YERVOY
Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Dose Escalation | Experimental | Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment. Receives: Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab |
| Phase 1b Dose Escalation Cohort A | Experimental | Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment Receives: Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab |
| Phase 1b Dose Escalation Cohort B | Experimental | Patients with favorable-risk RCC with clear cell component for first-line treatment. Receives: Drug: Sitravatinib; Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of patients experiencing treatment-emergent AEs
Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment
Measured: Through study completion, an average of 12 months
Secondary outcomes (3)
Objective Response Rate (ORR) in accordance with RECIST v1.1
Frequency of patients experiencing an objective response
Measured: Through duration of study, average of 10 months
Duration of Response (DOR)
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
Measured: 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
Measured: Through duration of study, average of 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2020
- Study start11 Aug 2020
- Primary completion30 Jun 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clear-Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirati Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Curtis Chin, MD, Study director, Mirati Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04518046
- Sponsor's protocol ID
- 516-008
- Status last verified
- Jun 2024
- First submitted
- 3 Aug 2020
- Last updated
- 5 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39794332
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Study of Sitravatinib in Combination With Nivolumab and Ipilimumab in Patients With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies
- ClinicalTrials.gov ID
- NCT04518046
- Acronym / sponsor ID
- 516-008
- Conditions
- Clear-Cell Renal Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Mirati Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Aug 2020 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 19 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Dose Escalation | Experimental | Drug: Sitravatinib, Drug: Nivolumab, Drug: IpilimumabPatients with poor- or intermediate-risk RCC with clear cell component for first-line treatment. |
| Phase 1b Dose Escalation Cohort A | Experimental | Drug: Sitravatinib, Drug: Nivolumab, Drug: IpilimumabPatients with poor- or intermediate-risk RCC with clear cell component for first-line treatment |
| Phase 1b Dose Escalation Cohort B | Experimental | Drug: Sitravatinib, Drug: Nivolumab, Drug: IpilimumabPatients with favorable-risk RCC with clear cell component for first-line treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed diagnosis of Clear-Cell Renal Cell Carcinoma (for initial cohorts under consideration)
- No prior treatment with systemic therapy (for initial cohorts under consideration)
- Adequate bone marrow and organ function
Key exclusion criteria (6 listed)
- Known or suspected presence of other cancer
- Brain metastases (for initial cohorts under consideration)
- Carcinomatous meningitis
- Immunocompromising conditions
- Impaired heart function
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitravatinibAlso: MGCD516Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases | Drug | Phase 1: Dose Escalation, Phase 1b Dose Escalation Cohort A, Phase 1b Dose Escalation Cohort B |
| NivolumabAlso: OPDIVONivolumab is a programmed death receptor-1 (PD-1) blocking antibody | Drug | Phase 1: Dose Escalation, Phase 1b Dose Escalation Cohort A, Phase 1b Dose Escalation Cohort B |
| IpilimumabAlso: YERVOYIpilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody | Drug | Phase 1: Dose Escalation, Phase 1b Dose Escalation Cohort A, Phase 1b Dose Escalation Cohort B |
Primary outcome
Frequency of patients experiencing treatment-emergent AEs
Time frame: Through study completion, an average of 12 months
Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment
3 secondary outcomes
Objective Response Rate (ORR) in accordance with RECIST v1.1
Time frame: Through duration of study, average of 10 months
Duration of Response (DOR)
Time frame: Through duration of study, average of 10 months
Progression-free Survival (PFS)
Time frame: Through duration of study, average of 10 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2024.
- Derived from this study: PubMed 39794332Msaouel 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Curtis Chin, MD study director
Mirati Therapeutics Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sitravatinib, Nivolumab and Ipilimumab in people with Clear-Cell Renal Cell Carcinoma, run by Mirati Therapeutics Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of patients experiencing treatment-emergent AEs (time frame: Through study completion, an average of 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04518046, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2024; AzTrials last refreshed its copy on 8 Nov 2026.