Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLC (ALKAZAR)

Nuvalent

Status and phase: Enrolling; Phase 3

Conditions: Non-small Cell Lung Cancer; Anaplastic Lymphoma Kinase-positive

Treatments: Drug: Alectinib; Drug: Neladalkib (NVL-655)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06765109

2024-517553-26 (EudraCT Number)

NVL-655-04

Details and patient eligibility

About

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).

Full description

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

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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450 participants in 2 patient groups

Neladalkib (NVL-655)

Experimental group

Description:

150mg taken orally once daily (QD)

Treatment:

Drug: Neladalkib (NVL-655)

Alectinib

Active Comparator group

Description:

600mg taken orally twice daily (BID)

Treatment:

Drug: Alectinib