Clinical Trials List
Protocol NumberNVL-655-04
NCT Number(ClinicalTrials.gov Identfier)NCT06765109
Active
2025-02-01 - 2030-12-31
Phase III
Recruiting4
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase 3 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 Compared to Alectinib in First-Line Treatment of Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer (ALKAZAR)
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Sponsor
PPD, Inc. Taiwan Branch
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Chin-Wei Kuo Division of General Internal Medicine
- Wu-Chou Su Division of Hematology & Oncology
- 林建佑 Division of General Internal Medicine
- 蔡政軒 Division of General Internal Medicine
- Chun-Hui Lee Division of Hematology & Oncology
- Chian-Wei Chen Division of General Internal Medicine
- Po-Lan Su Division of General Internal Medicine
- Seu-Chun Yang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 吳宗哲 Division of Hematology & Oncology
- James Chih-Hsin Yang Division of Hematology & Oncology
- 蔡子修 Division of General Internal Medicine
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- YEN-TING LIN Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- 廖斌志 Division of Hematology & Oncology
- 吳尚俊 Division of General Internal Medicine
- JIN-YUAN SHIH Division of General Internal Medicine
- 楊景堯 Division of General Internal Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- 廖唯昱 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Jen-Yu Hung
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
ALK-positive advanced non–small cell lung cancer (NSCLC)
Objectives
Primary Objective
To evaluate the efficacy of NVL-655 compared with alectinib in treatment-naïve patients with ALK-positive advanced non–small cell lung cancer (NSCLC).
Secondary Objectives
To evaluate additional efficacy endpoints of NVL-655 versus alectinib in treatment-naïve ALK-positive advanced NSCLC patients.
To assess and compare the safety and tolerability of NVL-655 and alectinib.
To evaluate and compare patient-reported outcomes (PROs), including health-related quality of life (QoL), lung cancer–related symptoms, patient functioning, and treatment-related side effects.
Exploratory Objectives
To investigate potential biomarkers and molecular mechanisms associated with response and resistance to NVL-655 and alectinib.
To evaluate progression-free survival (PFS) on subsequent therapy.
Test Drug
NVL-655
Alectinib HCl
Alectinib HCl
Active Ingredient
NVL-655
Alectinib HCl
Alectinib HCl
Dosage Form
110
030
030
Dosage
50 or 150 mg
150 MG
150 MG
Endpoints
Progression-Free Survival (PFS):
Defined as the time from randomization to the first occurrence of radiographically confirmed disease progression, as determined by blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first.
Defined as the time from randomization to the first occurrence of radiographically confirmed disease progression, as determined by blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first.
Inclution Criteria
Inclusion Criteria
Age ≥ 18 years.
Histologically or cytologically confirmed locally advanced (not eligible for multimodal treatment) or metastatic non–small cell lung cancer (NSCLC).
Documented evidence of an ALK rearrangement detected in tumor tissue or blood (circulating tumor DNA [ctDNA]) using a U.S. FDA-approved, PMDA-approved, or CE-marked local assay (or equivalent), including fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), immunohistochemistry (IHC), or next-generation sequencing (NGS). Other commercially available NGS assays approved by the sponsor may also be acceptable. Submission of this test result is required for eligibility.
No prior systemic anticancer therapy for NSCLC, including but not limited to targeted agents, antiangiogenic therapies, immunotherapies, or chemotherapy.
Adjuvant/neoadjuvant chemotherapy is permitted if completed >12 months prior to randomization.
Prior use of ALK tyrosine kinase inhibitors (e.g., alectinib) as adjuvant or neoadjuvant therapy is not allowed.
Must have measurable disease per RECIST v1.1, defined as ≥1 radiographically measurable target lesion (see Appendix 2).
Submission of pretreatment tumor tissue (archival sample, if available, or new biopsy specimen) for central analysis during screening.
Life expectancy ≥ 12 weeks.
ECOG Performance Status (PS) of 0, 1, or 2.
Adequate organ and bone marrow function as evidenced by the following laboratory parameters at the last assessment prior to randomization:
a. Bone marrow function:
Absolute neutrophil count (ANC) ≥ 1,500/µL
Platelet count > 75,000/µL
Hemoglobin ≥ 9 g/dL (without transfusion)
b. Renal function:
Estimated creatinine clearance ≥ 45 mL/min
c. Hepatic function:
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin within the normal range
All clinically significant toxicities from prior anticancer therapy (e.g., radiotherapy) must have resolved to ≤ Grade 1, except for adverse events (AEs) deemed not to pose a safety risk by the investigator.
Women of childbearing potential (WOCBP) must be surgically sterile or agree to abstain from sexual activity or use highly effective contraception (as defined by the Clinical Trial Facilitation Group [CTFG], 2020) from signing the informed consent form (ICF) through at least 6 months after the last dose of NVL-655 or 3 months after the last dose of alectinib, whichever is longer (or per local/national regulations).
Male participants with pregnant partners or WOCBP partners must use male contraception (condoms) from ICF signing until at least 4 months after the last dose of NVL-655 or alectinib (or longer per local/national requirements).
Must provide written informed consent and be willing and able to comply with all protocol-specified requirements.
Age ≥ 18 years.
Histologically or cytologically confirmed locally advanced (not eligible for multimodal treatment) or metastatic non–small cell lung cancer (NSCLC).
Documented evidence of an ALK rearrangement detected in tumor tissue or blood (circulating tumor DNA [ctDNA]) using a U.S. FDA-approved, PMDA-approved, or CE-marked local assay (or equivalent), including fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), immunohistochemistry (IHC), or next-generation sequencing (NGS). Other commercially available NGS assays approved by the sponsor may also be acceptable. Submission of this test result is required for eligibility.
No prior systemic anticancer therapy for NSCLC, including but not limited to targeted agents, antiangiogenic therapies, immunotherapies, or chemotherapy.
Adjuvant/neoadjuvant chemotherapy is permitted if completed >12 months prior to randomization.
Prior use of ALK tyrosine kinase inhibitors (e.g., alectinib) as adjuvant or neoadjuvant therapy is not allowed.
Must have measurable disease per RECIST v1.1, defined as ≥1 radiographically measurable target lesion (see Appendix 2).
Submission of pretreatment tumor tissue (archival sample, if available, or new biopsy specimen) for central analysis during screening.
Life expectancy ≥ 12 weeks.
ECOG Performance Status (PS) of 0, 1, or 2.
Adequate organ and bone marrow function as evidenced by the following laboratory parameters at the last assessment prior to randomization:
a. Bone marrow function:
Absolute neutrophil count (ANC) ≥ 1,500/µL
Platelet count > 75,000/µL
Hemoglobin ≥ 9 g/dL (without transfusion)
b. Renal function:
Estimated creatinine clearance ≥ 45 mL/min
c. Hepatic function:
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin within the normal range
All clinically significant toxicities from prior anticancer therapy (e.g., radiotherapy) must have resolved to ≤ Grade 1, except for adverse events (AEs) deemed not to pose a safety risk by the investigator.
Women of childbearing potential (WOCBP) must be surgically sterile or agree to abstain from sexual activity or use highly effective contraception (as defined by the Clinical Trial Facilitation Group [CTFG], 2020) from signing the informed consent form (ICF) through at least 6 months after the last dose of NVL-655 or 3 months after the last dose of alectinib, whichever is longer (or per local/national regulations).
Male participants with pregnant partners or WOCBP partners must use male contraception (condoms) from ICF signing until at least 4 months after the last dose of NVL-655 or alectinib (or longer per local/national requirements).
Must provide written informed consent and be willing and able to comply with all protocol-specified requirements.
Exclusion Criteria
Exclusion Criteria
Presence of a known oncogenic driver alteration other than ALK. The investigator should discuss eligibility with the sponsor in cases involving co-mutations.
Known hypersensitivity or allergic reaction to NVL-655, alectinib, or any of their excipients.
Major surgery within 4 weeks prior to randomization. Minor procedures (e.g., venous access device placement) are allowed, provided an adequate recovery period (clinically appropriate) has been ensured for wound healing.
Radiation therapy received within the following timeframes prior to randomization:
a. Radiation therapy (except palliative bone radiation) < 14 days
b. Palliative bone radiation < 48 hours
c. Stereotactic or small-field brain radiation < 7 days
d. Whole-brain radiation < 14 days
Clinically significant infection requiring systemic treatment and not adequately controlled.
Active tuberculosis, active hepatitis B, or active hepatitis C infection.
Active hepatitis B is defined as detectable HBV DNA above the lower limit of quantification.
Active hepatitis C is defined as detectable HCV RNA above the lower limit of quantification.
QTcF > 470 ms (confirmed by repeated measurements using the Fridericia correction formula), or a history of long QT syndrome or polymorphic ventricular tachycardia.
Clinically significant cardiovascular disease, including:
a. Within 3 months after randomization: cerebrovascular accident/stroke, myocardial infarction, unstable angina, or ≥ Grade 3 atrial fibrillation.
b. History of congestive heart failure (NYHA class ≥ II); second- or third-degree atrioventricular (AV) block (unless with pacemaker) or PR interval > 220 ms; or persistent cardiac arrhythmia of NCI-CTCAE Grade ≥ 2 (excluding atrial fibrillation).
Brain metastases with progressive neurologic symptoms or requiring escalating corticosteroid doses to control CNS disease. Patients receiving corticosteroids for CNS disease must be on a stable dose for at least 2 weeks before randomization. Asymptomatic leptomeningeal disease is allowed.
Symptomatic spinal cord compression.
Moderate to severe cognitive impairment or psychiatric disorder that, in the investigator’s judgment, may compromise the patient’s ability to comply with study requirements.
Active malignancy (other than ALK-positive solid tumor under study) requiring systemic therapy within 2 years prior to randomization.
Exceptions: non-melanoma skin cancer, in situ melanoma, cervical carcinoma in situ, papillary thyroid carcinoma, or localized, definitively treated breast or prostate cancer.
Patients on long-term hormonal therapy for a prior malignancy are allowed if the malignancy has been inactive for ≥ 2 years.
Concurrent use (within 14 days prior to randomization) of strong CYP3A4 inducers or strong CYP3A4 inhibitors.
Malabsorption syndrome or any gastrointestinal surgery/disease that may affect the oral absorption, distribution, metabolism, or excretion of study drugs.
Concurrent participation in another interventional clinical trial involving active systemic therapy.
Current evidence or history of interstitial lung disease (ILD) or pneumonitis, including noninfectious pneumonitis.
Pregnant or breastfeeding women. WOCBP must have a negative pregnancy test within 72 hours prior to initiation of study treatment.
Any medical condition or laboratory abnormality that, in the opinion of the investigator or sponsor, may pose a risk to the patient or confound interpretation of study results.
Presence of a known oncogenic driver alteration other than ALK. The investigator should discuss eligibility with the sponsor in cases involving co-mutations.
Known hypersensitivity or allergic reaction to NVL-655, alectinib, or any of their excipients.
Major surgery within 4 weeks prior to randomization. Minor procedures (e.g., venous access device placement) are allowed, provided an adequate recovery period (clinically appropriate) has been ensured for wound healing.
Radiation therapy received within the following timeframes prior to randomization:
a. Radiation therapy (except palliative bone radiation) < 14 days
b. Palliative bone radiation < 48 hours
c. Stereotactic or small-field brain radiation < 7 days
d. Whole-brain radiation < 14 days
Clinically significant infection requiring systemic treatment and not adequately controlled.
Active tuberculosis, active hepatitis B, or active hepatitis C infection.
Active hepatitis B is defined as detectable HBV DNA above the lower limit of quantification.
Active hepatitis C is defined as detectable HCV RNA above the lower limit of quantification.
QTcF > 470 ms (confirmed by repeated measurements using the Fridericia correction formula), or a history of long QT syndrome or polymorphic ventricular tachycardia.
Clinically significant cardiovascular disease, including:
a. Within 3 months after randomization: cerebrovascular accident/stroke, myocardial infarction, unstable angina, or ≥ Grade 3 atrial fibrillation.
b. History of congestive heart failure (NYHA class ≥ II); second- or third-degree atrioventricular (AV) block (unless with pacemaker) or PR interval > 220 ms; or persistent cardiac arrhythmia of NCI-CTCAE Grade ≥ 2 (excluding atrial fibrillation).
Brain metastases with progressive neurologic symptoms or requiring escalating corticosteroid doses to control CNS disease. Patients receiving corticosteroids for CNS disease must be on a stable dose for at least 2 weeks before randomization. Asymptomatic leptomeningeal disease is allowed.
Symptomatic spinal cord compression.
Moderate to severe cognitive impairment or psychiatric disorder that, in the investigator’s judgment, may compromise the patient’s ability to comply with study requirements.
Active malignancy (other than ALK-positive solid tumor under study) requiring systemic therapy within 2 years prior to randomization.
Exceptions: non-melanoma skin cancer, in situ melanoma, cervical carcinoma in situ, papillary thyroid carcinoma, or localized, definitively treated breast or prostate cancer.
Patients on long-term hormonal therapy for a prior malignancy are allowed if the malignancy has been inactive for ≥ 2 years.
Concurrent use (within 14 days prior to randomization) of strong CYP3A4 inducers or strong CYP3A4 inhibitors.
Malabsorption syndrome or any gastrointestinal surgery/disease that may affect the oral absorption, distribution, metabolism, or excretion of study drugs.
Concurrent participation in another interventional clinical trial involving active systemic therapy.
Current evidence or history of interstitial lung disease (ILD) or pneumonitis, including noninfectious pneumonitis.
Pregnant or breastfeeding women. WOCBP must have a negative pregnancy test within 72 hours prior to initiation of study treatment.
Any medical condition or laboratory abnormality that, in the opinion of the investigator or sponsor, may pose a risk to the patient or confound interpretation of study results.
The Estimated Number of Participants
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Taiwan
10 participants
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Global
450 participants
