Carcinoma, Non-Small-Cell LungPhase 2NCT02954991
Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer
A Phase 2 study testing Glesatinib, Sitravatinib and Mocetinostat in people with Carcinoma, Non-Small-Cell Lung, run by Mirati Therapeutics Inc. at 25 sites in United States.
Trial summary
The study will evaluate the clinical activity of nivolumab in combination with 3 separate investigational agents, glesatinib, sitravatinib, or mocetinostat. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Glesatinib, Sitravatinib and Mocetinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 161 participants
- Where
- 25 sitesUnited States
- Study dates
- 7 Nov 2016to 4 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of non-small cell lung cancer.
- Prior treatment with a checkpoint inhibitor (as appropriate per cohort)
- Adequate bone marrow and organ function
Who cannot join
- Uncontrolled tumor in the brain
- Unacceptable toxicity with prior checkpoint inhibitor
- Impaired heart function
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Texas Oncology - South Austin
Austin, Texas, 78745
Beverly Hills Cancer Center
Beverly Hills, California, 90211
Oncology Hematology Care-Blue Ash
Cincinnati, Ohio, 45242
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
USOR - Texas Oncology - Denison Cancer Center
Denison, Texas, 75020
Rocky Mountain Cancer Centers - Denver - Midtown
Denver, Colorado, 80218
Henry Ford Hospital
Detroit, Michigan, 48202
City of Hope National Medical Center
Duarte, California, 91010
Virginia Cancer Specialist
Fairfax, Virginia, 22031
Saint Francis Cancer Treatment Center
Grand Island, Nebraska, 68803
MD Anderson Cancer Center
Houston, Texas, 77030
University of California San Diego
La Jolla, California, 92093
Baptist Health
Louisville, Kentucky, 40207
University of Wisconsin
Madison, Wisconsin, 53792
Hematology Oncology Associates - Barnett Office
Medford, Oregon, 97504
Minnesota Oncology Hematology, P.A.
Minneapolis, Minnesota, 55404
University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, 55455
Vanderbilt University
Nashville, Tennessee, 37212
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of California San Francisco Comprehensive Cancer Center
San Francisco, California, 94115
University of California Los Angeles - Torrance - Community Cancer Care
Santa Clarita, California, 91355
Northwest Cancer Specialists, P.C.
Tualatin, Oregon, 97062
Texas Oncology - Tyler
Tyler, Texas, 75702
Yuma Regional Medical Center
Yuma, Arizona, 85364
About this study
Official title: A Parallel Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Advanced or Metastatic Non-Small Cell Lung Cancer
The study will evaluate the clinical activity of nivolumab in combination with 3 separate investigational agents, glesatinib, sitravatinib, or mocetinostat.
Read the detailed description
Glesatinib is an orally administered multi-targeted tyrosine kinase inhibitor (TKI) that primarily targets the Axl and Mesenchymal-Epithelial Transition (MET) receptors. Sitravatinib is an orally-available, potent small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Mocetinostat is an orally administered histone deacetylase (HDAC) inhibitor. Nivolumab is a human IgG monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response including anti-tumor immune response. Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone.
The study will begin with a lead-in dose escalation evaluation of two dose levels of each investigational agent in combination with nivolumab. Following completion of the lead-in dose escalation, enrollment into the Phase 2 study will proceed.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Glesatinib, Sitravatinib, Mocetinostat, Nivolumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlesatinibDrug
Also called MGCD265
Glesatinib is a small molecule multi-targeted receptor tyrosine kinase inhibitor
SitravatinibDrug
Also called MGCD516
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.
MocetinostatDrug
Also called MGCD01013
Mocetinostat is an HDAC inhibitor.
NivolumabDrug
Also called Opdivo
nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
| Study group | Role | What they receive |
|---|---|---|
| Glesatinib and Nivolumab | Experimental | Glesatinib oral tablet administered twice daily in combination with Nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week Receives: Drug: Glesatinib; Drug: Nivolumab |
| Sitravatinib and Nivolumab | Experimental | Sitravatinib oral capsule administered daily in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week Receives: Drug: Sitravatinib; Drug: Nivolumab |
| Mocetinostat and Nivolumab | Experimental | Mocetinostat oral capsule administered three times weekly in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week Receives: Drug: Mocetinostat; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
ORR is defined as the percentage of participants that were documented to have a confirmed complete response (CR) or partial response (PR) as defined by RECIST v1.1.
Measured: Up to 40.6 months
Secondary outcomes (5)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as any event that first occur or increase in severity on or after the first dose of study treatment and not more than 28 days after the last dose of study treatment and prior to the initiation of subsequent systemic anti- cancer therapy.
Any clinically significant changes in laboratory tests were recorded as TEAEs.
Measured: Day 1 up to 28 days after the last dose (median time on treatment was: CIT experienced 3.7 months; CIT naïve 4.8 months)
Duration of Response (DOR)
DOR was defined as the time in months from date of the first documentation of objective response (CR or PR) to the first documentation of objective progressive disease (PD) or to death due to any cause in the absence of documented PD. (Be aware, the population analyzed here is the Clinical Activity Evaluable Population and not the Full Analysis Set as used in outcome measure 1).
Measured: Up to 38.8 months
Progression Free Survival (PFS)
PFS was defined as the time from the first dose of study drug to the date of PD or death due to any cause in the absence of documented PD, whichever occurs first.
Measured: Up to 40.6 months
Overall Survival (OS)
OS was defined as the time from first dose of study drug to the date of death due to any cause.
Measured: Up to 43.8 months
Blood Plasma Concentrations
Predose (trough) concentrations for sitravatinib
Measured: Cycle 1 Day 1 through Cycle 5 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2016 (estimated)
- Study start7 Nov 2016
- Primary completion4 Nov 2021
- Study completion4 Nov 2021
Why it stopped: This study was terminated as a result of Sponsor portfolio reprioritization.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 161 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirati Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02954991
- Sponsor's protocol ID
- MRTX-500
- Status last verified
- Apr 2024
- First submitted
- 2 Nov 2016
- Last updated
- 22 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Liu J, Wang W, Wang K, Liu W, Zhao Y, Han X, Wang L, Jiang BH. HDAC1 and FOXK1 mediate EGFR-TKI resistance of non-small cell lung cancer through miR-33a silencing. J Transl Med. 2024 Aug 28;22(1):793. doi: 10.1186/s12967-024-05563-3.
PubMed 39198847
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Parallel Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Advanced or Metastatic Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02954991
- Acronym / sponsor ID
- MRTX-500
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated as a result of Sponsor portfolio reprioritization.
- Enrolment
- 161 participants (actual)
- Lead sponsor
- Mirati Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Nov 2016 (actual)
- Primary completion
- 4 Nov 2021 (actual)
- Study completion
- 4 Nov 2021 (actual)
- First posted
- 4 Nov 2016 (estimated)
- Results
- Posted 22 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will evaluate the clinical activity of nivolumab in combination with 3 separate investigational agents, glesatinib, sitravatinib, or mocetinostat.
Detailed description
Glesatinib is an orally administered multi-targeted tyrosine kinase inhibitor (TKI) that primarily targets the Axl and Mesenchymal-Epithelial Transition (MET) receptors. Sitravatinib is an orally-available, potent small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Mocetinostat is an orally administered histone deacetylase (HDAC) inhibitor. Nivolumab is a human IgG monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response including anti-tumor immune response. Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone.
The study will begin with a lead-in dose escalation evaluation of two dose levels of each investigational agent in combination with nivolumab. Following completion of the lead-in dose escalation, enrollment into the Phase 2 study will proceed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Glesatinib and Nivolumab | Experimental | Drug: Glesatinib, Drug: NivolumabGlesatinib oral tablet administered twice daily in combination with Nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week |
| Sitravatinib and Nivolumab | Experimental | Drug: Sitravatinib, Drug: NivolumabSitravatinib oral capsule administered daily in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week |
| Mocetinostat and Nivolumab | Experimental | Drug: Mocetinostat, Drug: NivolumabMocetinostat oral capsule administered three times weekly in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of non-small cell lung cancer.
- Prior treatment with a checkpoint inhibitor (as appropriate per cohort)
- Adequate bone marrow and organ function
Key exclusion criteria (3 listed)
- Uncontrolled tumor in the brain
- Unacceptable toxicity with prior checkpoint inhibitor
- 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 |
|---|---|---|
| GlesatinibAlso: MGCD265Glesatinib is a small molecule multi-targeted receptor tyrosine kinase inhibitor | Drug | Glesatinib and Nivolumab |
| SitravatinibAlso: MGCD516Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases. | Drug | Sitravatinib and Nivolumab |
| MocetinostatAlso: MGCD01013Mocetinostat is an HDAC inhibitor. | Drug | Mocetinostat and Nivolumab |
| NivolumabAlso: Opdivonivolumab is a programmed death receptor-1 (PD-1) blocking antibody | Drug | Glesatinib and Nivolumab, Mocetinostat and Nivolumab, Sitravatinib and Nivolumab |
Primary outcome
Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: Up to 40.6 months
ORR is defined as the percentage of participants that were documented to have a confirmed complete response (CR) or partial response (PR) as defined by RECIST v1.1.
5 secondary outcomes
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 up to 28 days after the last dose (median time on treatment was: CIT experienced 3.7 months; CIT naïve 4.8 months)
Duration of Response (DOR)
Time frame: Up to 38.8 months
Progression Free Survival (PFS)
Time frame: Up to 40.6 months
Overall Survival (OS)
Time frame: Up to 43.8 months
Blood Plasma Concentrations
Time frame: Cycle 1 Day 1 through Cycle 5 Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39198847Liu J, Wang W, Wang K, Liu W, Zhao Y, Han X, Wang L, Jiang BH. HDAC1 and FOXK1 mediate EGFR-TKI resistance of non-small cell lung cancer through miR-33a silencing. J Transl Med. 2024 Aug 28;22(1):793. doi: 10.1186/s12967-024-05563-3.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Glesatinib, Sitravatinib and Mocetinostat in people with Carcinoma, Non-Small-Cell Lung, run by Mirati Therapeutics Inc. at 25 sites 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 3 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: stopped early, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response Rate (ORR) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. (time frame: Up to 40.6 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 NCT02954991, 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 22 Apr 2024.