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

Not Recruiting

Trial ID: NCT01625234


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.

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

Stanford Investigator(s)

Heather Wakelee
Heather Wakelee

Winston Chen and Phyllis Huang Professor

Joel Neal, MD, PhD
Joel Neal, MD, PhD

Associate Professor of Medicine (Oncology)

Kavitha Ramchandran
Kavitha Ramchandran

Clinical Professor, Medicine - Oncology

Millie Das
Millie Das

Clinical Professor, Medicine - Oncology


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

   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

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.


drug: Phase I: X-396 (ensartinib)

drug: Phase II: X-396 (ensartinib)

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Danielle Pancirer

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