Clinical Trials /

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

NCT01625234

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: X396-CLI-101
  • NCT ID: NCT01625234

Conditions

  • Advanced Solid Tumors
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
X-396 (ensartinib)X-396 (ensartinib)

Purpose

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 60
      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 5 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), patients with asymptomatic CNS
      metastases, and patients with leptomeningeal disease.
    

Trial Arms

NameTypeDescriptionInterventions
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
  • X-396 (ensartinib)

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed diagnosis of advanced solid tumor
             malignancy. Patients may have received prior crizotinib and/or second generation ALK
             TKIs (patient must have progressed on alectinib).

             -For the expanded cohort portion of the study, patients must have NSCLC with ALK
             genomic alterations positive by FISH or IHC testing done centrally; however, patients
             will be allowed to enroll based on local ALK FISH or IHC 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. Patients entering this study will be asked to provide tissue for correlative testing
             (if available).

         11. Willingness and ability to comply with the trial and follow-up procedures.

         12. 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.

          3. Any major surgery, radiotherapy, or immunotherapy within the last 21 days.
             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. Concomitant use of herbal medications at least 7 days prior to the first dose of study
             drug and throughout participation in the trial.

          8. Females who are pregnant or breastfeeding.

          9. Presence of active gastrointestinal (GI) disease or other condition that will
             interfere significantly with the absorption, distribution, metabolism, or excretion of
             X-396.

         10. Clinically significant cardiovascular disease.

         11. 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.

         12. Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.

         13. 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.

         14. Inability or unwillingness to comply with study and/or follow-up procedures outlined
             in the protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:12 months
Safety Issue:
Description: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

Measure:Plasma Concentrations (Cmax, Tmax, AUC, half-life)
Time Frame:18 months
Safety Issue:
Description:To characterize the preliminary pharmacokinetics including Cmax, Tmax, AUC, half-life of X-396 given as a single agent
Measure:Preliminary Tumor Response
Time Frame:18 months
Safety Issue:
Description:To explore the preliminary clinical tumor response after treatment with X-396 (ensartinib) given as a single agent.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Xcovery Holding Company, LLC

Trial Keywords

  • Cancer
  • Tumors
  • ALK
  • NSCLC
  • Advanced Malignancies
  • Carcinoma, Non-Small-Cell Lung
  • Inflammatory Myofibroblastic Tumors

Last Updated

December 29, 2017