TriangleNCT02767804 · CITED IN SOURCE DOCUMENTS
eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2025-10-14
The primary purpose of this study is to evaluate the efficacy and safety of X-396 (ensartinib) 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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- Inclusion Criteria 1. 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 by an FDA-approved assay performed centrally. Patients must be ALK positive by local test prior to submitting tissue to the central lab. Randomization will occur after ALK positive confirmation is received from the central lab. 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. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2. (see Appendix A) 3. Life expectancy of at least 12 weeks. 4. Ability to swallow and retain oral medication. 5. Adequate organ system function, defined as follows: 1. Absolute neutrophil count (ANC) ≥1.5 x 109/L 2. Platelets ≥100 x 109/L 3. Hemoglobin ≥9 g/dL (≥90 g/L) Note that transfusions are allowed to meet the required hemoglobin level 4. Total bilirubin ≤1.5 times the upper limit of normal (ULN) 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if no liver involvement or ≤5 x ULN with liver involvement. 6. Creatinine \< 1.5 x ULN. If \>1.5 x ULN, patient may still be eligible if calculated creatinine clearance \>50 mL/min (0.83mL/s) as calculated by the Cockcroft-Gault method. 6. Brain metastases allowed if asymptomatic at study baseline. Patients with untreated brain metastases must not be on corticosteroids. If patients have neurological symptoms or signs due to CNS metastases, patients need to complete whole brain radiation or focal treatment at least 14 days before start of study treatment and be asymptomatic on stable or decreasing doses of corticosteroids at baseline. 7. 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. 8. 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. 9. Patients must be \>18 years-of-age. 10. Patients must have measurable disease per RECIST v. 1.1. 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. Note the following pertains to patients enrolled in France In France, a subject will be eligible for inclusion in this study only affiliated to the French Social Security system, and currently benefit from the corresponding rights and cover. Exclusion Criteria 1. 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). 2. Use of an investigational drug within 21 days prior to the first dose of study drug. Note that to be eligible, any drug-related toxicity should have recovered to Grade 1 or less, with the exception of alopecia. 3. Any chemotherapy within 4 weeks, or major surgery or radiotherapy within the last 14 days. 4. Patients with primary CNS tumors and leptomeningeal disease are ineligible. 5. Patients with a previous malignancy within the past 3 years (other than curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any cancer that is considered to be cured and have no impact on PFS and OS for the current NSCLC). 6. Concomitant systemic use of anticancer herbal medications. These should be stopped prior to study entry. 7. Patients receiving 1. strong CYP3A inhibitors (including, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit, grapefruit juice) 2. strong CYP3A inducers (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's Wort) 3. CYP3A substrates with narrow therapeutic window (including, but not limited to, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus). 8. Women 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 study medications. 10. Patients at risk for GI perforation. 11. Clinically significant cardiovascular disease including: 1. QTcF interval \>450 ms for men and \>470 ms for women, symptomatic bradycardia \<45 beats per minute or other significant ECG abnormalities in the investigator's opinion. 2. Clinically uncontrolled hypertension in the investigator's opinion (e.g., blood pressure \>160/100 mmHg; note that isolated elevated readings considered to not be indicative of uncontrolled hypertension are allowed). The following within 6 months prior to Cycle 1 Day 1: 1. Congestive heart failure (New York Heart Class III or IV). 2. Arrhythmia or conduction abnormality requiring medication. Note: patients with atrial fibrillation/flutter controlled by medication and arrhythmias controlled by pacemakers are eligible. 3. Severe/unstable angina, coronary artery/peripheral bypass graft, or myocardial infarction. 4. Cerebrovascular accident or transient ischemia. 12. 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 patient to receive protocol treatment. Patients with controlled hepatitis C, in the investigator's opinion, are allowed. Patients with known hepatitis B must be HBeAg and HB viral DNA negative for enrollment. Note that, because of the high prevalence, all patients in the Asia-Pacific region (except Australia, New Zealand, and Japan) must be tested and, if HBsAg positive, must be HBeAg and HB viral DNA negative for enrollment. 13. Known hypersensitivity to tartrazine, a dye used in the ensartinib 100 mg capsule. 14. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 15. 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. 16. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol. Note the following pertains to patients enrolled in France 17. In France, a subject will not be eligible when under legal protection.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Eligible patients with ALK+ NSCLC will receive oral X-396 (ensartinib) at 225mg QD with or without food until progression or unacceptable toxicity develops
- intervention Names
- Drug: X-396 (ensartinib)
- label
- X-396 (ensartinib)
- type
- EXPERIMENTAL
- description
- Eligible patients with ALK+ NSCLC will receive oral crizotinib at 250mg BID with or without food until progression or unacceptable toxicity develops
- intervention Names
- Drug: crizotinib
- label
- crizotinib
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- X-396 (ensartinib)
- description
- oral ALK inhibitor
- name
- X-396 (ensartinib)
- type
- DRUG
- arm Group Labels
- crizotinib
- description
- oral ALK inhibitor
- name
- crizotinib
- other Names
- Xalkori
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 290
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- as assessed by independent radiology review based on RECIST v. 1.1 criteria
- measure
- Progression-free survival (PFS)
- time Frame
- 36 months
- secondary Outcomes
- description
- Time in months from date of randomization to death due to any cause
- measure
- Overall survival (OS)
- time Frame
- 48 months
- description
- Based on IRR, time to CNS progression (based on IRR), objective response rate (based on IRR)
- measure
- CNS response rate
- time Frame
- 36 months
- description
- The proportion of patients in ITT who have an objective response (i.e., those who achieve a best response of CR or PR) per RECIST 1.1 criteria
- measure
- ORR based on independent radiology review
- time Frame
- 36 months
Full study description
- brief Summary
- The primary purpose of this study is to evaluate the efficacy and safety of X-396 (ensartinib) 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.
- detailed Description
- To evaluate the efficacy and safety of X-396 (ensartinib) 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), to obtain additional pharmacokinetic (PK) data from sparse PK sampling, 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, and to obtain germline DNA samples for possible pharmacogenetic analysis in the event that outliers with respect to efficacy, tolerability/safety, or exposure are identified.
Source references
- references
- citation
- Horn L, Wang Z, Wu G, Poddubskaya E, Mok T, Reck M, Wakelee H, Chiappori AA, Lee DH, Breder V, Orlov S, Cicin I, Cheng Y, Liu Y, Fan Y, Whisenant JG, Zhou Y, Oertel V, Harrow K, Liang C, Mao L, Selvaggi G, Wu YL. Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial. JAMA Oncol. 2021 Nov 1;7(11):1617-1625. doi: 10.1001/jamaoncol.2021.3523.
- pmid
- 34473194
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-6930f26a5157bc54f454
- requested nct id
- NCT02767804
- primary nct id
- NCT02767804
- source kind
- fda_spl_label
- source record id
- 17196ce1-224e-4359-ac54-39e035def74f
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- payload sha256
- bbb6769e39781ef1cb9575e5eaea2ac532d726297d74eb01c715f1291a85049e
- payload
- application numbers
- NDA218171
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-6930f26a5157bc54f454
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02767804
- occurrences
- context exact
- 14 CLINICAL STUDIES 14.1 TKI-naive ALK-Positive Locally Advanced or Metastatic NSCLC (eXALT3 Study) The efficacy of ENSACOVE was evaluated in eXALT3 (NCT02767804), an open-label, randomized, active-controlled, multicenter study in adult patients with locally advanced (stage IIIB following prior chemotherapy or chemoradi
- end
- 161
- exact text
- NCT02767804
- start
- 150
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00000.json
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- source json pointer
- /results/74/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 17196ce1-224e-4359-ac54-39e035def74f
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- d5d0923bc9a05bc405fc0484cb1726bd1719424ca2f35b5bcac78fe7c152ef1e
- spl effective time
- 20260217
- spl set id
- 1e1b2f79-678a-472a-b924-66909c8a4b2e
Preserved source evidence · Not medical advice