Phase 1/2 Study of X-396, an Oral ALK Inhibitor, in Patients With ALK-positive Non-Small Cell Lung Cancer
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
1 other identifier
interventional
131
1 country
14
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2012
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2012
CompletedFirst Submitted
Initial submission to the registry
June 15, 2012
CompletedFirst Posted
Study publicly available on registry
June 21, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 17, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
September 17, 2020
CompletedResults Posted
Study results publicly available
April 30, 2026
CompletedApril 30, 2026
September 1, 2025
8.3 years
June 15, 2012
December 6, 2024
April 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
28 Days
Secondary Outcomes (5)
Number of Participants With Preliminary Tumor Response in ALK Positive Patients at 225 mg QD
18 months
Plasma Concentrations Cmax for Day 1
24 hours
Plasma Tmax on Day 1
24 hours
Plasma Concentrations AUC on Day 1
0, 0.5h, 1.0h , 2.0 h, 4.0h, 6.0h, 8.0h, 24.0h,
Plasma Concentrations Half-life on Day 1
24 hours
Study Arms (2)
Phase I: X-396 (ensartinib)
EXPERIMENTALDose 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)
EXPERIMENTALRP2D 225mg stratified based on prior treatment and CNS activity
Interventions
Oral, ALK inhibitor
Expanded Cohort
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
City of Hope National Med Ctr
Duarte, California, 91010, United States
UCSD Moores Cancer Center
La Jolla, California, 92093, United States
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Stanford University
Stanford, California, 94305, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
New York University Langone Medical Center
New York, New York, 10016, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
Vanderbilt University
Nashville, Tennessee, 37240, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Wisconsin Carbone Cancer Ctr
Madison, Wisconsin, 53792, United States
Related Publications (2)
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: 21613408BACKGROUNDHorn 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: 29563138RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Vice President, Clinical Operations
- Organization
- Xcovery Holdings, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 15, 2012
First Posted
June 21, 2012
Study Start
June 1, 2012
Primary Completion
September 17, 2020
Study Completion
September 17, 2020
Last Updated
April 30, 2026
Results First Posted
April 30, 2026
Record last verified: 2025-09