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Neladalkib

Phase 3

Non-small Cell Lung Cancer | Small molecule | Oncology |Nuvalent, Inc.|Last Updated: Aug 25, 2026

Target and mechanism

Molecular targetALK
Target classKinase
ModalitySmall molecule

Also known as Neladalkib (NVL-655)

Success Probability

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Market & Valuation

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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 Sites158

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 387 trials

Recent Changes (Last 90 Days)

LOWAug 25, 2026NCT06765109lastUpdatePostDate: changed
LOWAug 25, 2026NCT06765109lastUpdatePostDate: changed
LOWJul 21, 2026NCT06765109lastUpdatePostDate: changed
LOWJul 13, 2026NCT06765109lastUpdatePostDate: changed
LOWJul 13, 2026NCT06765109lastUpdatePostDate: changed

Frequently asked questions about Neladalkib

What is Neladalkib used for?

Neladalkib (NVL-655) is an investigational small molecule being developed for non-small cell lung cancer (NSCLC) and locally advanced solid tumors. It is studied in patients with ALK rearrangement or activating ALK mutation, including those with anaplastic lymphoma kinase-positive NSCLC.

What does Neladalkib target?

Neladalkib targets ALK, a kinase enzyme. As a small molecule kinase inhibitor, it is designed to interfere with ALK-driven signaling in tumors that harbor ALK rearrangements or activating mutations.

Who is developing Neladalkib?

Neladalkib is being developed by Nuvalent, Inc., a biopharmaceutical company traded on NASDAQ under the ticker NUVL. The company is conducting clinical trials to evaluate the drug in patients with advanced solid tumors.

What phase is Neladalkib in?

Neladalkib is in clinical development. It is being evaluated in a Phase 1 trial (NCT05384626) and a Phase 3 trial (NCT06765109), both currently recruiting. The drug has not been approved by the FDA and remains investigational.

What clinical trials is Neladalkib in?

Neladalkib is being studied in two recruiting trials. NCT05384626 is a Phase 1 study in advanced NSCLC and other solid tumors with ALK alterations. NCT06765109 is a Phase 3 study in TKI-naive patients with advanced ALK-positive NSCLC.

Is Neladalkib the same as NVL-655?

Yes, Neladalkib is also known as NVL-655. Both names refer to the same investigational drug developed by Nuvalent, Inc. for the treatment of ALK-driven cancers.