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Neladalkib

Phase 3

Non-small Cell Lung Cancer | Small molecule | Oncology |Nuvalent, Inc.|Last Updated: Jul 21, 2026

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Trial Design
RandomizedACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment450
FDA Designations
BREAKTHROUGH_THERAPYORPHAN_DRUG
Clinical trial landscape

Neladalkib · 2 trials · 4 indications

Phase 3 1Phase 1 1
NCT06765109Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLCNon-small Cell Lung Cancer
RECRUITING450 Analytics
PHASE3RECRUITING
Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLC
Non-small Cell Lung CancerUnlock trial analytics
Study Endpoints
Primary Endpoints
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

Dose limiting toxicities (DLTs) (Phase 1)
Within the first 21 days of the first neladalkib (NVL-655) dose

Define the dose limiting toxicities (DLTs)

Recommended Phase 2 Dose (RP2D) (Phase 1)
Within 21 days of last patient dosed during escalation

To determine the RP2D

Objective Response Rate (ORR) (Phase 2)
2-3 years after first patient dosed.

To determine ORR as assessed by BICR

Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)
Approximately 3 years

Incidence and severity of treatment-emergent adverse events (TEAEs)

Area under the curve of repaglinide (Phase 2 DDI sub-study)
Pre-dose and up to 24 hours post-dose

To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of repaglinide

Area under the curve of midazolam (Phase 2 DDI sub-study)
Pre-dose and up to 24 hours post-dose

To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of midazolam

Area under the curve of neladalkib (NVL-655) (Phase 2 DDI sub-study)
Pre-dose and up to 24 hours post-dose

To determine the effect of itraconazole on the single oral dose PK of neladalkib (NVL-655)

Secondary Endpoints
Overall survival (OS)
Up to 5 years after first patient dosed
Progression-free survival (PFS) per investigator assessment
Up to 5 years after first patient dosed
Time to intracranial progression per BICR
Up to 5 years after first patient dosed
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Study Design & Arms
AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Neladalkib (NVL-655)EXPERIMENTAL150mg taken orally once daily (QD)
AlectinibACTIVE_COMPARATOR600mg taken orally twice daily (BID)
Phase 1 dose escalationEXPERIMENTALNeladalkib (NVL-655) oral daily dosing
Cohort 2aEXPERIMENTALPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received 1 prior 2nd-generation ALK TKI (ceritinib, alectinib, or brigatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.
Cohort 2bEXPERIMENTALPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.
Cohort 2cEXPERIMENTALPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received lorlatinib as the only prior ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy received prior to lorlatinib is allowed.
Cohort 2dEXPERIMENTALPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who are naïve to ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy is allowed.
Cohort 2eEXPERIMENTALPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
Cohort 2fEXPERIMENTALPatients with other solid tumors harboring an ALK rearrangement or activating ALK mutation, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists.
Cohort G (DDI sub-study)EXPERIMENTALPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI
Cohort H (DDI sub-study)EXPERIMENTALPatients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI
Interventions
NameTypeDescription
Neladalkib (NVL-655)DRUGOral tablet of Neladalkib (NVL-655)
AlectinibDRUGOral capsule of alectinib
MidazolamDRUGOral Solution of Midazolam
RepaglinideDRUGOral Tablet of Repaglinide
ItraconazoleDRUGOral Solution of Itraconazole
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Eligibility Criteria
Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites157

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 t...

Countries:United StatesArgentinaAustraliaAustriaBelgiumBrazilCanadaChileCzechiaDenmarkFranceGermanyGreeceHong KongHungaryItalyJapanMalaysiaMexicoNetherlandsPolandPortugalSingaporeSouth KoreaSpainSwitzerlandTaiwanThailandUnited Kingdom
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Competitive Landscape -Non-Small Cell Lung Cancer 394 trials
Recent Changes (Last 90 Days)
LOWJul 21, 2026NCT06765109lastUpdatePostDate: changed
LOWJul 13, 2026NCT06765109lastUpdatePostDate: changed
LOWJul 13, 2026NCT06765109lastUpdatePostDate: changed
LOWJun 2, 2026NCT06765109lastUpdatePostDate: changed
LOWJun 2, 2026NCT06765109lastUpdatePostDate: changed
LOWJun 2, 2026NCT06765109lastUpdatePostDate: changed
MEDIUMMay 28, 2026NCT05384626lastUpdatePostDate: changed
MEDIUMMay 28, 2026NCT05384626lastUpdatePostDate: changed
LOWMay 26, 2026NCT06765109primaryCompletionDate: changed
LOWMay 26, 2026NCT05384626primaryCompletionDate: changed
LOWMay 24, 2026NCT06765109studyFirstPostDate: changed
LOWMay 24, 2026NCT05384626studyFirstPostDate: changed