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

NCT02767804 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: X396-CLI-301
• Study Type: interventional
• Target: 290
• Locations: 20 countries
• Sites: 72

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.

Conditions

Non-small Cell Lung Cancer

Keywords

ALK-positive NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

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

  36 months

Secondary Outcomes (3)

• Overall survival (OS)

  48 months

• CNS response rate

  36 months

• ORR based on independent radiology review

  36 months

Study Arms (2)

X-396 (ensartinib)

EXPERIMENTAL

Eligible patients with ALK+ NSCLC will receive oral X-396 (ensartinib) at 225mg QD with or without food until progression or unacceptable toxicity develops

Drug: X-396 (ensartinib)

crizotinib

ACTIVE COMPARATOR

Eligible patients with ALK+ NSCLC will receive oral crizotinib at 250mg BID with or without food until progression or unacceptable toxicity develops

Drug: crizotinib

Interventions

X-396 (ensartinib) DRUG

oral ALK inhibitor

X-396 (ensartinib)

crizotinib DRUG

oral ALK inhibitor

Also known as: Xalkori

crizotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Xcovery Holdings, Inc.: lead

Study Sites (72)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University Cancer & Blood Center

Athens, Georgia, 30607, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Sanatorio Parque S.A.

Rosario, Argentina

Location

Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Location

Chris O Brien Lifehouse

Camperdown, Australia

Location

Catholic University of Louvain (UCL) - Site Mont Godinne

Yvoir, 5530, Belgium

Location

Instituto do Câncer do Estado de São Paulo

São Paulo, São Paulo, 01246-000, Brazil

Location

Hospital de Câncer de Barretos - Fundação Pio XII

São Paulo, São Paulo, 14784-400, Brazil

Location

Hospital Haroldo Juaçaba - Instituto do Cancêr do Ceará

Fortaleza, 60351-010, Brazil

Location

Fundacao do ABC Faculdade de Medicina do ABC

São Paulo, Brazil

Location

Infirmière recherche Clinique, IUCPQ

Québec, Quebec, G1V 4G5, Canada

Location

Anhui Provincial Hospital

Hefei, Anhui, 230001, China

Location

Beijing Chao Yang Hospital

Beijing, Beijing Municipality, 100020, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Peking University Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Beijing Chest Hospital,Capital Medical University

Beijing, Beijing Municipality, 101149, China

Location

Fujian Provincial Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

Guangdong General Hospital

Guangzhou, Guangdong, 510080, China

Location

Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050011, China

Location

Hunan Cancer Hospital

Changsha, Hu'nan, 410006, China

Location

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

Wuhan, Hubei, 420104, China

Location

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

Wuhan, Hubei, 430030, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

Nanjing General Hospital

Nanjing, Jiangsu, 210002, China

Location

The First Bethune Hospital of Jilin University

Changchun, Jilin, 130000, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266071, China

Location

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Peking University Cancer Hospital

Beijing, 100142, China

Location

Zhejiang Cancer Hospital

Hangzhou, China

Location

Vítkovická Nemocnice , a.s.

Ostrava-Vitkovice, 70384, Czechia

Location

Krajská zdravotní, a.s., Masarykova nemocnice

Ústí nad Labem, 40113, Czechia

Location

CHRU Lille

Lille, 59000, France

Location

Hopital Arnaud de Villeneuve

Montpellier, 34298, France

Location

CHU de Rennes Hôpital Pontchaillou

Rennes, 35033, France

Location

Hopital Saint-Louis

Vellefaux, France

Location

Charite Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Lungen Clinic Grosshansdorf

Großhansdorf, 22927, Germany

Location

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Elizabeth Hospital

Hong Kong, Hong Kong

Location

The University of Hong Kong/Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Rabin Medical Center Institute of Oncology, Davidoff Center

Petah Tikva, 49100, Israel

Location

IEO Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Centro Operativo Studi Clinici S.C.Oncologia Medica

Perugia, 06132, Italy

Location

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

Sondrio, 20121, Italy

Location

VU Medical Center

Amsterdam, 1007 MB, Netherlands

Location

Maastricht University Medical Centre (MUMC)

Maastricht, 6229HX, Netherlands

Location

Medical University of Gdansk

Gdansk, Poland

Location

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

Moscow, 115478, Russia

Location

LLC "Vitamed"

Moscow, 121309, Russia

Location

Moscow City Oncology Hospital #63

Moscow, 143423, Russia

Location

BIH of Omsk Region "Clinical Oncology Dispensary"

Omsk, Russia

Location

Pavlov First Medical University

Saint Petersburg, 197022, Russia

Location

Petrov Research Institute of Oncology

Saint Petersburg, Russia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Son Ltatzer

Palma de Mallorca, 07198, Spain

Location

Trakya University Balkan Oncology Hospital

Edirne, 22030, Turkey (Türkiye)

Location

Blackpool Victoria Hospital

Blackwood, FY3 8NR, United Kingdom

Location

Southmead Hospital

Bristol, BS10 5NB, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Kings Mill Hospital

Nottingham, NG17 4JL, United Kingdom

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ensartinib; Crizotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Giovanni Selvaggi, MD

  CEO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2016
• First Posted: May 10, 2016
• Study Start: June 1, 2016
• Primary Completion: December 30, 2025
• Study Completion: December 31, 2025
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2); RU (6); BE (1); CZ (2); HK (4); BR (4); GB (4); CA (1); US (4); TU (1); ES (4); AU (3); KR (2); CN (21); NL (2); AR (1); FR (4); DE (2); PL (1); IT (3)