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

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

Inclusion criteria

• Histologically or cytologically confirmed locally advanced (not amenable for multimodality treatment) or metastatic Non-small Cell Lung Cancer (NSCLC)
• Documented Anaplastic Lymphoma Kinase (ALK) rearrangement via testing of tissue or blood
• 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)
• Measurable disease (1 or more target lesions per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
• Pretreatment tumor tissue

Exclusion criteria

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