Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Phase 1/2 Study of X-396, an Oral ALK Inhibitor, in Patients With ALK-positive Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01625234
Recruitment Status : Completed
First Posted : June 21, 2012
Last Update Posted : October 6, 2021
Information provided by (Responsible Party):
Xcovery Holding Company, LLC

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Non-small Cell Lung Cancer Drug: Phase I: X-396 (ensartinib) Drug: Phase II: X-396 (ensartinib) Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 131 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : June 2012
Actual Primary Completion Date : September 17, 2020
Actual Study Completion Date : September 17, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: 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
Drug: Phase I: X-396 (ensartinib)
Oral, ALK inhibitor
Other Name: ensartinib

Experimental: Phase II: X-396 (ensartinib)
RP2D 225mg stratified based on prior treatment and CNS activity
Drug: Phase II: X-396 (ensartinib)
Expanded Cohort
Other Name: ensartinib

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 12 months ]
    To evaluate the safety/tolerability of X-396 (ensartinib) and determine the maximum tolerated dose (MTD) of X-396 as a single agent.

Secondary Outcome Measures :
  1. Plasma Concentrations (Cmax, Tmax, AUC, half-life) [ Time Frame: 18 months ]
    To characterize the preliminary pharmacokinetics including Cmax, Tmax, AUC, half-life of X-396 given as a single agent

  2. Preliminary Tumor Response [ Time Frame: 18 months ]
    To explore the preliminary clinical tumor response after treatment with X-396 (ensartinib) given as a single agent.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01625234

Layout table for location information
United States, California
City of Hope National Med Ctr
Duarte, California, United States, 91010
UCSD Moores Cancer Center
La Jolla, California, United States, 92093
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Stanford University
Stanford, California, United States, 94305
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Maryland
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
New York University Langone Medical Center
New York, New York, United States, 10016
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
Vanderbilt University
Nashville, Tennessee, United States, 37240
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin Carbone Cancer Ctr
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Xcovery Holding Company, LLC
Publications of Results:
Other Publications:
Layout table for additonal information
Responsible Party: Xcovery Holding Company, LLC Identifier: NCT01625234    
Other Study ID Numbers: X396-CLI-101
First Posted: June 21, 2012    Key Record Dates
Last Update Posted: October 6, 2021
Last Verified: October 2021
Keywords provided by Xcovery Holding Company, LLC:
Advanced Malignancies
Carcinoma, Non-Small-Cell Lung
Inflammatory Myofibroblastic Tumors
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action