A Study to Evaluate and Compare the Efficacy and Safety of XZP-3621 Versus Crizotinib

NCT05204628 | Unknown Phase 3 DMC

• 1 other identifier: XZP-3621-3001
• Study Type: interventional
• Target: 238
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, multicenter, Phase III, open-label study will evaluate the efficacy and safety of XZP-3621 versus crizotinib and to evaluate the pharmacokinetics of XZP-3621 in Chinese participants with treatment-naive ALK-positive advanced NSCLC. Participants will be randomized 1:1 into one of the two treatment groups to receive either XZP-3621 (500 milligrams \[mg\] once daily \[QD\]) or crizotinib (250 mg BID) orally, respectively.

Conditions

Non-small Cell Lung Cancer

Keywords

XZP-3621; Crizotinib

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by investigators using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 or to death from any cause, whichever occurred first.

  From the date of randomization to the date of the first documented disease progression or death, whichever occurred first (up to overall period of approximately 30 months)

Secondary Outcomes (12)

• Progression-Free Survival (PFS)

  From the date of randomization to the date of the first documented disease progression or death, whichever occurred first (up to overall period of approximately 30 months).

• Overall Survival (OS)

  From randomization until death (up to approximately 30 months).

• Overall Response Rate (ORR)

  From randomization until death (up to approximately 30 months)

• Duration of Response (DOR)

  From randomization until death (up to approximately 30 months)

• Disease Control Rate (DCR)

  Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study (up to overall period of approximately 30 months)

Study Arms (2)

XZP-3621

EXPERIMENTAL

Participants will receive XZP-3621 tablets orally at a dose of 500 mg QD with food until disease progression, unacceptable toxicity withdrawal of consent, or death, whichever occurred first.

Drug: XZP-3621

Crizotinib

ACTIVE COMPARATOR

Participants will receive crizotinib capsules orally at a dose of 250 mg BID with or without food until disease progression, unacceptable toxicity withdrawal of consent, or death, whichever occurred first.

Drug: Crizotinib

Interventions

XZP-3621 DRUG

XZP-3621 tablets will be administered orally at a dose of 500 mg QD until disease progression, unacceptable toxicity withdrawal of consent, or death, whichever occurred first.

XZP-3621

Crizotinib DRUG

Crizotinib capsules will be administered orally at a dose of 250 mg BID until disease progression, unacceptable toxicity withdrawal of consent, or death, whichever occurred first.

Crizotinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be 18-75 years-of-age;
• Patients with Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB and IIIC not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive where ALK status is determined by the NMPA-approved (for use in China) Ventana (D5F3) immunohistochemistry (IHC) test or FISH or PCR or NGS, Sufficient tumor tissue available to perform ALK status is required if not determined.
• 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, defined as follows:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L; Platelets ≥100 x 109/L; Hemoglobin ≥9 g/dL (≥90 g/L)
• Total bilirubin ≤1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 \*ULN if no liver involvement or ≤5 \* ULN with liver involvement.
• Creatinine \< 1.5 \*ULN. If \>1.5 \* ULN, patient may still be eligible if calculated creatinine clearance \>50 mL/min (0.83mL/s) as calculated by the Cockcroft-Gault method.
• No prior systemic treatment for advanced or recurrent NSCLC (Stage IIIB and IIIC not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
• Tumor Requirements: At least 1 extracranial measurable target lesion per RECIST v. 1.1 that has not been previously irradiated.
• Serum pregnancy test (for females of childbearing potential) negative at screening.
• Ability to understand the nature of this trial and give written informed consent.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Patients with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in PFS and OS for the current NSCLC).
• Any GI disorder that may affect absorption of oral medications, such as mal-absorption syndrome or status post-major bowel resection ;
• Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C virus (HCV) (eg, in case of known HBsAg or HCV antibody positivity), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness;
• Clinically significant vascular (both arterial and venous) and non-vascular cardiac conditions, (active or within 3 months prior to enrollment), which may include, but are not limited to:
• Arterial disease such as cerebral vascular accident/stroke (including Transient Ischemic Attack -TIA), myocardial infarction, unstable angina;
• Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary embolism;
• Non-vascular cardiac disease such as congestive heart failure (New York Heart Association Classification Class ≥ II), second-degree or third-degree AV block (unless paced) or any AV block with PR \>220 msec; or ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, bradycardia defined as \<50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read Electrocardiogram (ECG) with QTc \>470 msec, or congenital long QT syndrome;
• Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (eg, uncontrolled hyperglycemia, current gallstone disease) in the last month prior to randomization;
• History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis;
• Concurrent use of known strong CYP3A4 inhibitors and inducers (consult the sponsor if in doubt whether a food or a drug falls into any of the above categories) within 7 days prior to the first dose of XZP-3621 or crizotinib.
• Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation;
• Pregnant female patients; breastfeeding female patients;
• History of organ transplant;
• Co-administration of anti-cancer therapies other than those administered in this study;

Sponsors & Collaborators

• Xuanzhu Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

Jilin Province Cancer Hospital

Changchun, Jilin, 132000, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

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

• Ying Cheng, MD

  Jilin Province Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Li

CONTACT

+86-18566662772; lichao@xuanzhubio.com

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: December 20, 2021
• First Posted: January 24, 2022
• Study Start: February 7, 2022
• Primary Completion: May 7, 2025
• Study Completion: July 1, 2025
• Last Updated: January 24, 2022

Record last verified: 2021-11

Locations

CN (1)