Clinical trial NCT06765109: Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLC
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Anaplastic Lymphoma Kinase-positive
Keywords: NSCLC
Lung cancer
Lung neoplasms
Lung diseases
ALK positive NSCLC
TKI naive
ALK TKI naive
Treatment naive
Lead sponsor: Nuvalent Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-09
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multicenter, randomized, controlled, open-label, Phase 3 study designed to demonstrate that neladalkib (NVL-655) is superior to alectinib in prolonging progression-free survival (PFS) in patients with treatment-naïve, Anaplastic Lymphoma Kinase (ALK) positive, advanced Non-Small Cell Lung Cancer (NSCLC).

Detailed description: Patients will be randomized in a 1:1 ratio (approximately 225 in each arm) to receive either neladalkib (NVL-655) or alectinib.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed locally advanced (not amenable for multimodality treatment) or metastatic Non-small Cell Lung Cancer (NSCLC)
2. Documented Anaplastic Lymphoma Kinase (ALK) rearrangement via testing of tissue or blood
3. No prior systemic anticancer treatment for NSCLC (adjuvant/neoadjuvant chemotherapy allowed if 12 months prior to randomization; prior ALK tyrosine kinase inhibitor \[TKI\] such as alectinib is not allowed in any setting)
4. Measurable disease (1 or more target lesions per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1)
5. Pretreatment tumor tissue (archived or a fresh biopsy)
6. Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2

Exclusion Criteria:

1. Patient's cancer has a known oncogenic driver alteration other than ALK.
2. Known allergy/hypersensitivity to excipients of neladalkib or alectinib.
3. Ongoing or recent radiotherapy as per protocol-specified timeframes prior to randomization
4. Major surgery within 4 weeks prior to randomization
5. Uncontrolled clinically relevant infection requiring systemic therapy
6. Known active tuberculosis, or active Hepatitis B or C
7. QT corrected for heart rate by Fridericia's formula (QTcF) \> 470 msec on repeated assessments
8. Clinically significant cardiovascular disease
9. Brain metastases associated with progressive neurological symptoms or requiring increasing doses of corticosteroids to control CNS disease
10. Active malignancy requiring therapy within 2 years prior to randomization

Primary outcomes:
measure: Progression-free survival (PFS) per blinded independent central review (BICR)
timeFrame: Up to 5 years after first patient dosed
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 5 years after first patient dosed
measure: Progression-free survival (PFS) per investigator assessment
timeFrame: Up to 5 years after first patient dosed
measure: Time to intracranial progression per BICR
timeFrame: Up to 5 years after first patient dosed
measure: Intracranial objective response rate (IC-ORR)
timeFrame: Up to 5 years after first patient dosed
measure: Intracranial duration of response (IC-DOR)
timeFrame: Up to 5 years after first patient dosed
measure: Objective response rate (ORR)
timeFrame: Up to 5 years after first patient dosed
measure: Duration of response (DOR)
timeFrame: Up to 5 years after first patient dosed
measure: Intracranial progression per investigator assessment
timeFrame: Up to 5 years after first patient dosed
measure: Treatment-emergent adverse events (TEAEs) and changes in clinically relevant laboratory parameters
timeFrame: Up to 5 years after first patient dosed
measure: Patient-reported measures in health-related quality of life (QoL)
timeFrame: Up to 5 years after first patient dosed
measure: Patient-reported measures in lung cancer symptoms and side effects of treatment
timeFrame: Up to 5 years after first patient dosed
measure: Patient-reported measures in patient functioning
timeFrame: Up to 5 years after first patient dosed
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University Center for Advanced Medicine
state: Missouri
city: New Hyde Park
country: United States
facility: Clinical Research Alliance Inc.
state: New York
Study officials:
affiliation: Nuvalent Inc.
name: Viola Zhu, MD, PhD
role: STUDY_DIRECTOR
References: