Clinical Trial 18685

Cancer Type:
Interventions:X-396 (Ensartinib)

Study Type: Treatment
Phase of Study: Phase I/II

  • Alberto Chiappori


Study Title

Phase I/II, First-in-Human, Dose-Escalation Study of X-396 in Patients with Advanced Solid Tumors and Expansion Phase in Patients with ALK+ Non-Small Cell Lung Cancer


This research study is being done to evaluate the safety of an investigational drug, X-396, and to determine the best dose to use for future studies. "Investigational" means that X-396 has not been approved by the United States Food and Drug Administration (FDA) for use outside of clinical studies. X-396 has not been given to humans before this study. Different genes have been shown to change and affect the development and growth of tumors. Based on laboratory studies, X-396 blocks the effects of at least 2 of these genes (ALK and MET).


Primary: *To evaluate the safety/tolerability of X-396 and determine the maximum tolerated dose (MTD) of X-396 as a single agent. Secondary: *To characterize the preliminary pharmacokinetics (PK) of X-396 given as a single agent. *To explore the preliminary biological activity and clinical tumor response after treatment with X-396 given as a single agent. Exploratory: *To observe the correlation between PK and clinical endpoints. *To evaluate the status of exploratory biomarkers and correlate with clinical outcome. *To obtain germline DNA samples for possible pharmacogenetic analysis in the event that outliers with respect to efficacy, tolerability/safety, or exposure are identified.

Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy. Participants may have received prior crizotinib and/or second generation ALK TKIs (participant must have progressed on alectinib).
  • For the expanded cohort portion of the study, participants must have Non-small Cell Lung Cancer (NSCLC) with ALK genomic alterations positive by FISH or IHC testing done centrally; however, potential participants will be allowed to enroll based on local ALK FISH or IHC 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 central nervous system (CNS) metastases may be allowed to enroll.
  • Males willing to use adequate contraceptive measures.
  • Females who are not of child-bearing potential, and females of child-bearing potential who agree to use adequate contraceptive measures.
  • Must be ≥ 18 years of age.
  • 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).
  • Participants entering this study will be asked to provide tissue for correlative testing (if available).
  • 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.

  • Exclusion Criteria

  • 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.
  • 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.
  • Prior stem cell transplant.
  • 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.
  • 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.