Clinical Trial 18677

Cancer Type:
Interventions:Crizotinib; X-396 (Ensartinib); Xalkori (Crizotinib)

Study Type: Treatment
Phase of Study: Phase III

  • Alberto Chiappori


Study Title

XALT3: Phase 3 Randomized Study Comparing X-396 to Crizotinib in Anaplastic Lymphoma Kinase (ALK) Positive Non-Small Cell Lung Cancer (NSCLC) Patients


The primary purpose of this study is to evaluate the efficacy and safety of ensartinib (X-396) ) vs. crizotinib in patients with ALK-positive non-small cell lung cancer that have received up to 1 prior chemotherapy regimen and no prior ALK inhibitor.


Primary: *To evaluate the efficacy and safety of X-396 vs. crizotinib in patients with ALK-positive NSCLC that have received up to 1 prior chemotherapy regimen and no prior ALK tyrosine kinase inhibitor (TKI). Secondary: *To obtain additional pharmacokinetic (PK) data on X-396 from sparse PK sampling from patients at selected sites. Exploratory: *To compare the quality of life (QoL) in patients receiving X-396 vs. crizotinib. *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 or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. Enrollment will be allowed based on positive Abbott FISH or Ventana IHC, performed locally or centrally. Patients may have received up to 1 prior chemotherapy regimen for metastatic disease, which may also include maintenance therapy. Note that patients that have received adjuvant or neoadjuvant chemotherapy and developed metastatic disease within 6 months from the end of that therapy would be considered to have received 1 prior regimen for metastatic disease.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2.
  • Life expectancy of at least 12 weeks.
  • Ability to swallow and retain oral medication.
  • Adequate organ system function.
  • Brain metastases allowed if asymptomatic at study baseline.
  • Men with partners of childbearing potential willing to use adequate contraceptive measures during the study and for 90 days after the last dose of study medication.
  • Women who are not of child-bearing potential, and women of child-bearing potential who agree to use adequate contraceptive measures during the study and for 90 days after the last dose of study medication, and who have a negative serum or urine pregnancy test within 1 week prior to initial trial treatment.
  • Must be at least 18 years of age.
  • Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1.
  • 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 that have previously received an ALK TKI or PD-1/PD-L1 therapy, and patients currently receiving cancer therapy (i.e., other targeted therapies, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization).
  • Use of an investigational drug within 21 days prior to the first dose of study drug.
  • Any chemotherapy within 4 weeks, or major surgery or radiotherapy within the last 14 days.
  • Primary central nervous system (CNS) tumors and leptomeningeal disease.
  • A previous malignancy within the past 3 years.
  • Concomitant systemic use of anticancer herbal medications. These should be stopped prior to study entry.
  • Receiving strong CYP3A inhibitors, strong CYP3A inducers, CYP3A substrates with narrow therapeutic window..
  • Women 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 study medications.
  • Patients at risk for GI perforation
  • Clinically significant cardiovascular disease.
  • Patients who are immunosuppressed (including known HIV infection), have a serious active infection at the time of treatment, have interstitial lung disease/pneumonitis, or have any serious underlying medical condition that would impair the ability of the participant 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.