Advanced Solid TumorsPhase 1/2NCT01625234
Phase 1/2 Study of X-396, an Oral ALK Inhibitor, in Patients With ALK-positive Non-Small Cell Lung Cancer
A Phase 1/2 study testing Phase I: X-396 (ensartinib) and Phase II: X-396 (ensartinib) in people with Advanced Solid Tumors and Non-small Cell Lung Cancer, run by Xcovery Holdings, Inc. at 14 sites in United States.
Trial summary
This is the first human study to use X-396 (ensartinib), a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the largest amount of X-396 that can be safely given to humans (the maximum tolerated dose). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Non-small Cell Lung Cancer
- What is being tested?
- Phase I: X-396 (ensartinib) and Phase II: X-396 (ensartinib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 14 sitesUnited States
- Study dates
- Jun 2012to 17 Sep 2020
- Phase
- Phase 1/2
- 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
- Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy. Patients may be ALK TKI-naive or may have received prior crizotinib and/or second generation ALK TKIs. In addition, patients with a known ALK 1198 mutation will be allowed.
- -For the expanded cohort portion of the study, patients must have NSCLC with ALK genomic alterations; however, patients will be allowed to enroll based on local FDA-approved ALK results.
- Eastern Cooperative Group ECOG) Performance Status score of 0 or 1.
- Ability to swallow and retain oral medication.
- Adequate organ system function.
- Patients with treated or untreated asymptomatic CNS metastases may be allowed to enroll.
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- Male patients willing to use adequate contraceptive measures.
- Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures.
- Patients must be ≥ 18 years of age.
- Patients must have measurable or evaluable disease for the dose escalation portion of the study and measurable disease for the expanded cohort portion of the study (except for patients in the CNS metastases and leptomeningeal cohorts).
- Willingness and ability to comply with the trial and follow-up procedures.
- Ability to understand the nature of this trial and give written informed consent.
Who cannot join
- Patients currently receiving cancer therapy.
- Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of X-396. A minimum of 10 days between treatment and X-396 and 2 days between ALK TKI and X-396.
- Any major surgery, radiotherapy, or immunotherapy within the last 21 days (focal radiation does not require a washout period; ≥4 weeks for WBRT). Chemotherapy regimens with delayed toxicity within the last 4 weeks. Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks.
- Prior stem cell transplant.
- Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically related to X-396 (e.g., crizotinib) or to the active ingredient of X-396.
- Patients with primary CNS tumors are ineligible.
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- Patients receiving CYP3A substrates with narrow therapeutic indices, strong CYP3A inhibitors, and strong CYP3A inducers.
- Concomitant use of herbal medications at least 7 days prior to the first dose of study drug and throughout participation in the trial.
- Females who are pregnant or breastfeeding.
- Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of X-396.
- Clinically significant cardiovascular disease.
- Patients who are immunosuppressed (including known HIV infection), have a serious active infection at the time of treatment, have known hepatitis C, or have any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol or would impart excessive risk associated with study participation that would make it inappropriate for the patient to be enrolled.
- Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
City of Hope National Med Ctr
Duarte, California, 91010
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
UCSD Moores Cancer Center
La Jolla, California, 92093
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Wisconsin Carbone Cancer Ctr
Madison, Wisconsin, 53792
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Vanderbilt University
Nashville, Tennessee, 37240
New York University Langone Medical Center
New York, New York, 10016
Providence Portland Medical Center
Portland, Oregon, 97213
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: Phase 1/2, First-in-Human, Dose-Escalation Study of X-396 (Ensartinib) in Patients With Advanced Solid Tumors and Expansion Phase in Patients With ALK-positive Non-Small Cell Lung Cancer
This is the first human study to use X-396 (ensartinib), a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the largest amount of X-396 that can be safely given to humans (the maximum tolerated dose). Once the recommended Phase 2 dose has been determined, an expansion phase will assess the preliminary anti-tumor activity of X-396 in ALK-positive non-small cell lung cancer. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the efficacy of X-396.
Read the detailed description
This is the first study of X-396 (ensartinib) in humans and the investigational drug will be given as a once or twice daily oral dose in 28 day cycles until there is disease progression or unacceptable safety issues. X-396 will be given to small groups of patients (1 - 6) at each dose level and the patients will be observed to see if there are any adverse safety effects. As long as there are no unacceptable safety issues after 28 days, the dose of X-396 will be increased for the next group of patients. This process will continue until the maximum tolerated dose (MTD) of X-396 is reached. Once the MTD is reached, up to 170 additional patients will also be given X-396 to further determine the activity of X-396 in patients with ALK-positive non-small cell lung cancer. These additional patients will be enrolled in the following expansion cohorts: ALK TKI-naïve patients, patients that progressed on crizotinib, patients that progressed on one or more 2nd generation ALK TKIs (patients may or may not have also received prior crizotinib), including patients with asymptomatic CNS metastases.
- Conditions
- Advanced Solid Tumors, Non-small Cell Lung Cancer
- Being tested
- Phase I: X-396 (ensartinib), Phase II: X-396 (ensartinib)
- Keywords
- Cancer, Tumors, ALK, NSCLC, Advanced Malignancies, Carcinoma, Non-Small-Cell Lung, Inflammatory Myofibroblastic Tumors
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phase I: X-396 (ensartinib)Drug
Also called ensartinib
Oral, ALK inhibitor
Phase II: X-396 (ensartinib)Drug
Also called ensartinib
Expanded Cohort
| Study group | Role | What they receive |
|---|---|---|
| Phase I: X-396 (ensartinib) | Experimental | Dose escalation starting at 25 mg, oral once or twice a day, 28-day cycle. Number of Cycles: until progression or unacceptable toxicity develops Receives: Drug: Phase I: X-396 (ensartinib) |
| Phase II: X-396 (ensartinib) | Experimental | RP2D 225mg stratified based on prior treatment and CNS activity Receives: Drug: Phase II: X-396 (ensartinib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
To evaluate the safety/tolerability of X-396 (ensartinib) and determine the maximum tolerated dose (MTD) of X-396 as a single agent.
Measured: 28 Days
Secondary outcomes (5)
Number of Participants With Preliminary Tumor Response in ALK Positive Patients at 225 mg QD
To explore the preliminary clinical tumor response after treatment with X-396 (ensartinib) given as a single agent in ALK positive patients at 225 mg QD.
Subjects were assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 criteria (and CNS lesions were also assessed by modified Response Assessment in Neuro-Oncology). Assessments by CT or MRI were performed after every even cycle of treatment. All assessments were to be performed within 7 days of the scheduled day of assessment. Tumor lesions followed on physical examination must have been assessed on Day 1 of each cycle and at the End-of-Study Treatment Visit.
Measured: 18 months
Plasma Concentrations Cmax for Day 1
To characterize the preliminary pharmacokinetics including Cmax f X-396 given as a single agent
Measured: 24 hours
Plasma Tmax on Day 1
To characterize the preliminary pharmacokinetics including T max of X-396 given as a single agent
Measured: 24 hours
Plasma Concentrations AUC on Day 1
To characterize the preliminary pharmacokinetics including AUC of X-396 given as a single agent
Measured: 0, 0.5h, 1.0h , 2.0 h, 4.0h, 6.0h, 8.0h, 24.0h,
Plasma Concentrations Half-life on Day 1
To characterize the preliminary pharmacokinetics including half life of X-396 given as a single agent
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2012 (estimated)
- Study startJun 2012
- Primary completion17 Sep 2020
- Study completion17 Sep 2020
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 (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xcovery Holdings, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01625234
- Sponsor's protocol ID
- X396-CLI-101
- Status last verified
- Sep 2025
- First submitted
- 15 Jun 2012
- Last updated
- 30 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31. doi: 10.1158/0008-5472.CAN-10-3879. Epub 2011 May 25.
PubMed 21613408Horn L, Infante JR, Reckamp KL, Blumenschein GR, Leal TA, Waqar SN, Gitlitz BJ, Sanborn RE, Whisenant JG, Du L, Neal JW, Gockerman JP, Dukart G, Harrow K, Liang C, Gibbons JJ, Holzhausen A, Lovly CM, Wakelee HA. Ensartinib (X-396) in ALK-Positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study. Clin Cancer Res. 2018 Jun 15;24(12):2771-2779. doi: 10.1158/1078-0432.CCR-17-2398. Epub 2018 Mar 21.
PubMed 29563138
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2, First-in-Human, Dose-Escalation Study of X-396 (Ensartinib) in Patients With Advanced Solid Tumors and Expansion Phase in Patients With ALK-positive Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01625234
- Acronym / sponsor ID
- X396-CLI-101
- Conditions
- Advanced Solid Tumors, Non-small Cell Lung Cancer
- Keywords
- Cancer, Tumors, ALK, NSCLC, Advanced Malignancies, Carcinoma, Non-Small-Cell Lung, Inflammatory Myofibroblastic Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Xcovery Holdings, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- 17 Sep 2020 (actual)
- Study completion
- 17 Sep 2020 (actual)
- First posted
- 21 Jun 2012 (estimated)
- Results
- Posted 30 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is the first human study to use X-396 (ensartinib), a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the largest amount of X-396 that can be safely given to humans (the maximum tolerated dose). Once the recommended Phase 2 dose has been determined, an expansion phase will assess the preliminary anti-tumor activity of X-396 in ALK-positive non-small cell lung cancer. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the efficacy of X-396.
Detailed description
This is the first study of X-396 (ensartinib) in humans and the investigational drug will be given as a once or twice daily oral dose in 28 day cycles until there is disease progression or unacceptable safety issues. X-396 will be given to small groups of patients (1 - 6) at each dose level and the patients will be observed to see if there are any adverse safety effects. As long as there are no unacceptable safety issues after 28 days, the dose of X-396 will be increased for the next group of patients. This process will continue until the maximum tolerated dose (MTD) of X-396 is reached. Once the MTD is reached, up to 170 additional patients will also be given X-396 to further determine the activity of X-396 in patients with ALK-positive non-small cell lung cancer. These additional patients will be enrolled in the following expansion cohorts: ALK TKI-naïve patients, patients that progressed on crizotinib, patients that progressed on one or more 2nd generation ALK TKIs (patients may or may not have also received prior crizotinib), including patients with asymptomatic CNS metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I: X-396 (ensartinib) | Experimental | Drug: Phase I: X-396 (ensartinib)Dose escalation starting at 25 mg, oral once or twice a day, 28-day cycle. Number of Cycles: until progression or unacceptable toxicity develops |
| Phase II: X-396 (ensartinib) | Experimental | Drug: Phase II: X-396 (ensartinib)RP2D 225mg stratified based on prior treatment and CNS activity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy. Patients may be ALK TKI-naive or may have received prior crizotinib and/or second generation ALK TKIs. In addition, patients with a known ALK 1198 mutation will be allowed.
- -For the expanded cohort portion of the study, patients must have NSCLC with ALK genomic alterations; however, patients will be allowed to enroll based on local FDA-approved ALK results.
- Eastern Cooperative Group ECOG) Performance Status score of 0 or 1.
- Ability to swallow and retain oral medication.
- Adequate organ system function.
Key exclusion criteria (15 listed)
- Patients currently receiving cancer therapy.
- Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of X-396. A minimum of 10 days between treatment and X-396 and 2 days between ALK TKI and X-396.
- Any major surgery, radiotherapy, or immunotherapy within the last 21 days (focal radiation does not require a washout period; ≥4 weeks for WBRT). Chemotherapy regimens with delayed toxicity within the last 4 weeks. Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks.
- Prior stem cell transplant.
- Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically related to X-396 (e.g., crizotinib) or to the active ingredient of X-396.
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 |
|---|---|---|
| Phase I: X-396 (ensartinib)Also: ensartinibOral, ALK inhibitor | Drug | Phase I: X-396 (ensartinib) |
| Phase II: X-396 (ensartinib)Also: ensartinibExpanded Cohort | Drug | Phase II: X-396 (ensartinib) |
Primary outcome
Maximum Tolerated Dose
Time frame: 28 Days
To evaluate the safety/tolerability of X-396 (ensartinib) and determine the maximum tolerated dose (MTD) of X-396 as a single agent.
5 secondary outcomes
Number of Participants With Preliminary Tumor Response in ALK Positive Patients at 225 mg QD
Time frame: 18 months
Plasma Concentrations Cmax for Day 1
Time frame: 24 hours
Plasma Tmax on Day 1
Time frame: 24 hours
Plasma Concentrations AUC on Day 1
Time frame: 0, 0.5h, 1.0h , 2.0 h, 4.0h, 6.0h, 8.0h, 24.0h,
Plasma Concentrations Half-life on Day 1
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21613408Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31. doi: 10.1158/0008-5472.CAN-10-3879. Epub 2011 May 25.
- Results publication: PubMed 29563138Horn L, Infante JR, Reckamp KL, Blumenschein GR, Leal TA, Waqar SN, Gitlitz BJ, Sanborn RE, Whisenant JG, Du L, Neal JW, Gockerman JP, Dukart G, Harrow K, Liang C, Gibbons JJ, Holzhausen A, Lovly CM, Wakelee HA. Ensartinib (X-396) in ALK-Positive Non-Small Cell Lung Cancer: Results from a First-in-Human Phase I/II, Multicenter Study. Clin Cancer Res. 2018 Jun 15;24(12):2771-2779. doi: 10.1158/1078-0432.CCR-17-2398. Epub 2018 Mar 21.
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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.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Phase I: X-396 (ensartinib) and Phase II: X-396 (ensartinib) in people with Advanced Solid Tumors and Non-small Cell Lung Cancer, run by Xcovery Holdings, Inc. at 14 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 12 inclusion and 15 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 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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 combined 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.
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 30 Apr 2026). 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?
Maximum Tolerated Dose (time frame: 28 Days). 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 NCT01625234, which also lists 2 linked publications.
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 30 Apr 2026.