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AzTrials

Non-small Cell Lung CancerPhase 3NCT02767804

eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients

A Phase 3 study testing X-396 (ensartinib) and crizotinib in people with Non-small Cell Lung Cancer, run by Xcovery Holdings, Inc. at 72 sites in 20 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
X-396 (ensartinib) and crizotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
290 participants
Where
72 sitesin 20 countries
Study dates
Jun 2016to 31 Dec 2025
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2. (see Appendix A)
  • Life expectancy of at least 12 weeks.
  • Ability to swallow and retain oral medication.
  • Adequate organ system function, defined as follows:
  • Absolute neutrophil count (ANC) ≥1.5 x 109/L
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  • Platelets ≥100 x 109/L
  • Hemoglobin ≥9 g/dL (≥90 g/L) Note that transfusions are allowed to meet the required hemoglobin level
  • Total bilirubin ≤1.5 times the upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if no liver involvement or ≤5 x ULN with liver involvement.
  • 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.
  • 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.
  • 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.
  • Patients must be >18 years-of-age.
  • Patients must have measurable disease per 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.
  • 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.

Who cannot join

  • 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. Note that to be eligible, any drug-related toxicity should have recovered to Grade 1 or less, with the exception of alopecia.
  • Any chemotherapy within 4 weeks, or major surgery or radiotherapy within the last 14 days.
  • Patients with primary CNS tumors and leptomeningeal disease are ineligible.
  • 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).
  • Concomitant systemic use of anticancer herbal medications. These should be stopped prior to study entry.
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  • Patients receiving
  • strong CYP3A inhibitors (including, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit, grapefruit juice)
  • strong CYP3A inducers (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's Wort)
  • CYP3A substrates with narrow therapeutic window (including, but not limited to, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).
  • 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 including:
  • 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.
  • 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:
  • Congestive heart failure (New York Heart Class III or IV).
  • Arrhythmia or conduction abnormality requiring medication. Note: patients with atrial fibrillation/flutter controlled by medication and arrhythmias controlled by pacemakers are eligible.
  • Severe/unstable angina, coronary artery/peripheral bypass graft, or myocardial infarction.
  • Cerebrovascular accident or transient ischemia.
  • 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.
  • Known hypersensitivity to tartrazine, a dye used in the ensartinib 100 mg capsule.
  • 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.
  • Note the following pertains to patients enrolled in France
  • In France, a subject will not be eligible when under legal protection.

Trial locations and contacts

72 sites in 20 countries.

72 sites in 20 countries

China21 sites

  • Beijing Chao Yang Hospital

    Beijing, Beijing Municipality, 100020

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100032

  • Peking University Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • Beijing Chest Hospital,Capital Medical University

    Beijing, Beijing Municipality, 101149

  • Peking University Cancer Hospital

    Beijing, 100142

  • The First Bethune Hospital of Jilin University

    Changchun, Jilin, 130000

  • Jilin Cancer Hospital

    Changchun, Jilin, 130012

  • Hunan Cancer Hospital

    Changsha, Hu'nan, 410006

  • Fujian Provincial Cancer Hospital

    Fuzhou, Fujian, 350014

  • Guangdong General Hospital

    Guangzhou, Guangdong, 510080

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310022

  • Zhejiang Cancer Hospital

    Hangzhou

  • Anhui Provincial Hospital

    Hefei, Anhui, 230001

  • Nanjing General Hospital

    Nanjing, Jiangsu, 210002

  • The Affiliated Hospital of Qingdao University

    Qingdao, Shandong, 266071

  • Shanghai Chest Hospital

    Shanghai, Shanghai Municipality, 200030

  • The First Hospital of China Medical University

    Shenyang, Liaoning, 110001

  • Fourth Hospital of Hebei Medical University

    Shijiazhuang, Hebei, 050011

  • Union Hospital of Tongji Medical College of Huazhong Science and Techology University

    Wuhan, Hubei, 420104

  • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

    Wuhan, Hubei, 430030

  • Hubei Cancer Hospital

    Wuhan, Hubei, 430079

Other trials in China

Russia6 sites

  • Federal State Budgetary Scientific Institution Russian Oncological Scientific Center named after N.N. Blokhin

    Moscow, 115478

  • LLC "Vitamed"

    Moscow, 121309

  • Moscow City Oncology Hospital #63

    Moscow, 143423

  • BIH of Omsk Region "Clinical Oncology Dispensary"

    Omsk

  • Pavlov First Medical University

    Saint Petersburg, 197022

  • Petrov Research Institute of Oncology

    Saint Petersburg

Other trials in Russia

United States4 sites

  • University Cancer & Blood Center

    Athens, Georgia, 30607

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Brazil4 sites

  • Hospital Haroldo Juaçaba - Instituto do Cancêr do Ceará

    Fortaleza, 60351-010

  • Instituto do Câncer do Estado de São Paulo

    São Paulo, São Paulo, 01246-000

  • Hospital de Câncer de Barretos - Fundação Pio XII

    São Paulo, São Paulo, 14784-400

  • Fundacao do ABC Faculdade de Medicina do ABC

    São Paulo

Other trials in Brazil

France4 sites

  • CHRU Lille

    Lille, 59000

  • Hopital Arnaud de Villeneuve

    Montpellier, 34298

  • CHU de Rennes Hôpital Pontchaillou

    Rennes, 35033

  • Hopital Saint-Louis

    Vellefaux

Other trials in France

Hong Kong4 sites

  • Prince of Wales Hospital

    Hong Kong

  • Queen Elizabeth Hospital

    Hong Kong

  • The University of Hong Kong/Queen Mary Hospital

    Hong Kong

  • Prince of Wales Hospital

    Shatin

Other trials in Hong Kong

Spain4 sites

  • Hospital del Mar

    Barcelona, 08003

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08025

  • Hospital Vall d'Hebrón

    Barcelona, 08035

  • Hospital Son Ltatzer

    Palma de Mallorca, 07198

Other trials in Spain

United Kingdom4 sites

  • Blackpool Victoria Hospital

    Blackwood, FY3 8NR

  • Southmead Hospital

    Bristol, BS10 5NB

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Metropolitan Borough of Wirral, CH63 4JY

  • Kings Mill Hospital

    Nottingham, NG17 4JL

Other trials in United Kingdom

Australia3 sites

  • Border Medical Oncology Research Unit

    Albury, New South Wales, 2640

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales

  • Chris O Brien Lifehouse

    Camperdown

Other trials in Australia

Italy3 sites

  • IEO Istituto Europeo di Oncologia

    Milan, 20141

  • Centro Operativo Studi Clinici S.C.Oncologia Medica

    Perugia, 06132

  • Azienda Socio Sanitaria Territoriale (ASST) della Valtellina e dell'Alto Laria

    Sondrio, 20121

Other trials in Italy

Czechia2 sites

  • Vítkovická Nemocnice , a.s.

    Ostrava-Vitkovice, 70384

  • Krajská zdravotní, a.s., Masarykova nemocnice

    Ústí nad Labem, 40113

Other trials in Czechia

Germany2 sites

  • Charite Campus Virchow-Klinikum

    Berlin, 13353

  • Lungen Clinic Grosshansdorf

    Großhansdorf, 22927

Other trials in Germany

Israel2 sites

  • Hadassah Medical Center

    Jerusalem, 9112001

  • Rabin Medical Center Institute of Oncology, Davidoff Center

    Petah Tikva, 49100

Other trials in Israel

Netherlands2 sites

  • VU Medical Center

    Amsterdam, 1007 MB

  • Maastricht University Medical Centre (MUMC)

    Maastricht, 6229HX

Other trials in Netherlands

South Korea2 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Asan Medical Center

    Seoul, 05505

Other trials in South Korea

Argentina1 site

  • Sanatorio Parque S.A.

    Rosario

Other trials in Argentina

Belgium1 site

  • Catholic University of Louvain (UCL) - Site Mont Godinne

    Yvoir, 5530

Other trials in Belgium

Canada1 site

  • Infirmière recherche Clinique, IUCPQ

    Québec, Quebec, G1V 4G5

Other trials in Canada

Poland1 site

  • Medical University of Gdansk

    Gdansk

Other trials in Poland

Turkey (Türkiye)1 site

  • Trakya University Balkan Oncology Hospital

    Edirne, 22030

Other trials in Turkey (Türkiye)

About this study

Official title: Phase 3 Randomized Study Comparing X-396 (Ensartinib) 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 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.

Read the 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.

Being tested
X-396 (ensartinib), crizotinib
Keywords
ALK-positive NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • X-396 (ensartinib)Drug

    oral ALK inhibitor

  • crizotinibDrug

    Also called Xalkori

    oral ALK inhibitor

Study groups in NCT02767804
Study groupRoleWhat they receive
X-396 (ensartinib)ExperimentalEligible patients with ALK+ NSCLC will receive oral X-396 (ensartinib) at 225mg QD with or without food until progression or unacceptable toxicity develops
Receives: Drug: X-396 (ensartinib)
crizotinibActive comparatorEligible patients with ALK+ NSCLC will receive oral crizotinib at 250mg BID with or without food until progression or unacceptable toxicity develops
Receives: Drug: crizotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    as assessed by independent radiology review based on RECIST v. 1.1 criteria

    Measured: 36 months

Secondary outcomes (3)

  1. Overall survival (OS)

    Time in months from date of randomization to death due to any cause

    Measured: 48 months

  2. CNS response rate

    Based on IRR, time to CNS progression (based on IRR), objective response rate (based on IRR)

    Measured: 36 months

  3. ORR based on independent radiology review

    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

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2016 (estimated)
  2. Study startJun 2016
  3. Primary completion30 Dec 2025 (estimated)
  4. Study completion31 Dec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
290 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02767804
Sponsor's protocol ID
X396-CLI-301
Status last verified
Oct 2025
First submitted
30 Apr 2016
Last updated
14 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34473194

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing X-396 (ensartinib) and crizotinib in people with Non-small Cell Lung Cancer, run by Xcovery Holdings, Inc. at 72 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 72 sites in China, Russia, United States, Brazil, France and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02767804, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2025; AzTrials last refreshed its copy on 6 Nov 2026.

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