Anaplastic Lymphoma Kinase-positive, Non-small Cell Lung Cancer
Conditions
Keywords
NSCLC, Lung cancer, Lung neoplasms, Lung diseases, ALK positive NSCLC, TKI naive, ALK TKI naive, Treatment naive
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.
Interventions
Oral tablet of Neladalkib (NVL-655)
DRUGAlectinib
Oral capsule of alectinib
Sponsors
Nuvalent Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) per blinded independent central review (BICR) | Up to 5 years after first patient dosed | Time from randomization to BICR-assessed radiographic disease progression or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial duration of response (IC-DOR) | Up to 5 years after first patient dosed | Time from first intracranial response (IC-CR or IC-PR) to radiographic intracranial disease progression or death |
| Objective response rate (ORR) | Up to 5 years after first patient dosed | Proportion of patients with a complete response or partial response |
| Duration of response (DOR) | Up to 5 years after first patient dosed | Time from first response (complete or partial) to radiographic disease progression or death |
| Intracranial progression per investigator assessment | Up to 5 years after first patient dosed | Time to investigator-assessed intracranial progression |
| Treatment-emergent adverse events (TEAEs) and changes in clinically relevant laboratory parameters | Up to 5 years after first patient dosed | Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters |
| Patient-reported measures in health-related quality of life (QoL) | Up to 5 years after first patient dosed | Changes in patient-reported outcomes (PROs) assessed by the European Organization for Research and Treatment of Cancer QoL core questionnaire - Cancer (EORTC QLQ-C30) |
| Patient-reported measures in lung cancer symptoms and side effects of treatment | Up to 5 years after first patient dosed | Changes in PROs assessed by the European Organization for Research and Treatment of Cancer QoL - Lung Cancer module (EORTC QLQ-LC29) |
| Patient-reported measures in patient functioning | Up to 5 years after first patient dosed | Changes in PROs assessed by the European Quality of Life (EuroQol) 5-dimension questionnaire (EQ-5D-5L) |
| Time to intracranial progression per BICR | Up to 5 years after first patient dosed | Time from randomization to the first BICR-assessed occurrence of disease progression in the central nervous system (CNS) |
| Overall survival (OS) | Up to 5 years after first patient dosed | Time from randomization to death |
| Intracranial objective response rate (IC-ORR) | Up to 5 years after first patient dosed | Proportion of patients with a confirmed intracranial response (intracranial complete response \[IC-CR\] or intracranial partial response \[IC-PR\]) among patients with measurable CNS disease at baseline |
| Progression-free survival (PFS) per investigator assessment | Up to 5 years after first patient dosed | Time from randomization to investigator-assessed radiographic disease progression or death |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Portugal, Singapore, South Korea, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States
Contacts
CONTACTNuvalent Clinical Trials
STUDY_DIRECTORKelly Curtis, MD
Nuvalent Inc.
Outcome results
None listed