TriangleNCT01625234 · CITED IN SOURCE DOCUMENTS
Phase 1/2 Study of X-396, an Oral ALK Inhibitor, in Patients With ALK-positive Non-Small Cell Lung Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1, PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2026-04-30
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Maximum Tolerated Dose
Number of Participants With Preliminary Tumor Response in ALK Positive Patients at 225 mg QD
Plasma Concentrations Cmax for Day 1
Plasma Tmax on Day 1
Plasma Concentrations AUC on Day 1
Plasma Concentrations Half-life on Day 1
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: 1. 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. 2. Eastern Cooperative Group ECOG) Performance Status score of 0 or 1. 3. Ability to swallow and retain oral medication. 4. Adequate organ system function. 5. Patients with treated or untreated asymptomatic CNS metastases may be allowed to enroll. 6. Male patients willing to use adequate contraceptive measures. 7. Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures. 8. Patients must be ≥ 18 years of age. 9. 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). 10. Willingness and ability to comply with the trial and follow-up procedures. 11. Ability to understand the nature of this trial and give written informed consent. Exclusion Criteria: 1. Patients currently receiving cancer therapy. 2. 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. 3. 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. 4. Prior stem cell transplant. 5. 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. 6. Patients with primary CNS tumors are ineligible. 7. Patients receiving CYP3A substrates with narrow therapeutic indices, strong CYP3A inhibitors, and strong CYP3A inducers. 8. Concomitant use of herbal medications at least 7 days prior to the first dose of study drug and throughout participation in the trial. 9. Females who are pregnant or breastfeeding. 10. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of X-396. 11. Clinically significant cardiovascular disease. 12. 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. 13. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 14. 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. 15. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Dose escalation starting at 25 mg, oral once or twice a day, 28-day cycle. Number of Cycles: until progression or unacceptable toxicity develops
- intervention Names
- Drug: Phase I: X-396 (ensartinib)
- label
- Phase I: X-396 (ensartinib)
- type
- EXPERIMENTAL
- description
- RP2D 225mg stratified based on prior treatment and CNS activity
- intervention Names
- Drug: Phase II: X-396 (ensartinib)
- label
- Phase II: X-396 (ensartinib)
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Phase I: X-396 (ensartinib)
- description
- Oral, ALK inhibitor
- name
- Phase I: X-396 (ensartinib)
- other Names
- ensartinib
- type
- DRUG
- arm Group Labels
- Phase II: X-396 (ensartinib)
- description
- Expanded Cohort
- name
- Phase II: X-396 (ensartinib)
- other Names
- ensartinib
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SEQUENTIAL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 131
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- To evaluate the safety/tolerability of X-396 (ensartinib) and determine the maximum tolerated dose (MTD) of X-396 as a single agent.
- measure
- Maximum Tolerated Dose
- time Frame
- 28 Days
- secondary Outcomes
- description
- 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.
- measure
- Number of Participants With Preliminary Tumor Response in ALK Positive Patients at 225 mg QD
- time Frame
- 18 months
- description
- To characterize the preliminary pharmacokinetics including Cmax f X-396 given as a single agent
- measure
- Plasma Concentrations Cmax for Day 1
- time Frame
- 24 hours
- description
- To characterize the preliminary pharmacokinetics including T max of X-396 given as a single agent
- measure
- Plasma Tmax on Day 1
- time Frame
- 24 hours
- description
- To characterize the preliminary pharmacokinetics including AUC of X-396 given as a single agent
- measure
- Plasma Concentrations AUC on Day 1
- time Frame
- 0, 0.5h, 1.0h , 2.0 h, 4.0h, 6.0h, 8.0h, 24.0h,
- description
- To characterize the preliminary pharmacokinetics including half life of X-396 given as a single agent
- measure
- Plasma Concentrations Half-life on Day 1
- time Frame
- 24 hours
Full study description
- brief 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). 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.
Source references
- references
- citation
- 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.
- pmid
- 21613408
- type
- BACKGROUND
- citation
- Horn 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.
- pmid
- 29563138
- type
- RESULT
Source notices and limitations
Discovery and provenance
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- occurrences
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- 458 patients with locally advanced or metastatic ALK-positive NSCLC in the following trials: eXALT3 Study (N=143) [see Clinical Studies ( 14.1 ) ], Study 101 (NCT01625234, N=98), Study BTP-28311 (NCT02959619, N=35), and Study BTP-42322 (NCT03215693, N=182). Patients received ENSACOVE 225 mg orally once daily, with or without foo
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Preserved source evidence · Not medical advice