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Repotrectinib

Phase 3

Carcinoma, Non-Small-Cell Lung | Small molecule | Oncology |Bristol-Myers Squibb Company|Last Updated: Sep 4, 2026

Target and mechanism

Molecular targetNTRK3, NTRK2, CD74, ROS1, NTRK1, SDC4
Target classInhibitor
ModalitySmall molecule

Also known as Oral repotrectinib (TPX-0005)

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment190

FDA Designations

No designations recorded

Clinical trial landscape

Repotrectinib · 6 trials · 7 indications

Phase 3 1Phase 1 5
NCT06140836A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)Carcinoma, Non-Small-Cell Lung
ACTIVE NOT_RECRUITING190 Analytics
PHASE3ACTIVE NOT_RECRUITING
A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)
Carcinoma, Non-Small-Cell LungUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression-free Survival (PFS) as per Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Up to approximately 41 months
Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of AUC (0-T) of Probe Substrate With Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains metformin, digoxin, and rosuvastatin.

Cohort 1: AUC (0-T) of Probe Substrate Without Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains metformin, digoxin, and rosuvastatin.

Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Probe Substrate With Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains metformin, digoxin, and rosuvastatin.

Cohort 1: AUC(INF) of Probe Substrate Without Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains metformin, digoxin, and rosuvastatin.

Cohort 1: Maximum Observed Plasma Concentration (Cmax) of Probe Substrate With Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains metformin, digoxin, and rosuvastatin

Cohort 1: Cmax of Probe Substrate Without Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains metformin, digoxin, and rosuvastatin

Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to 48 Hours Post Dose (AUC (0-48)) of Metformin With Repotrectinib
Up to approximately Day 17 post dose
Cohort 1: AUC (0-48) of Metformin Without Repotrectinib
Up to approximately Day 17 post dose
Cohort 1: Renal Clearance (CLR) of Metformin in Urine
Up to approximately Day 16 post dose
Cohort 2: AUC (0-T) of Probe Substrate With Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)

Cohort 2: AUC (0-T) of Probe Substrate Without Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)

Cohort 2: AUC (INF) of Probe Substrate With Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)

Cohort 2: AUC (INF) of Probe Substrate Without Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)

Cohort 2: Cmax of Probe Substrate With Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)

Cohort 2: Cmax of Probe Substrate Without Repotrectinib
Up to approximately Day 17 post dose

Probe substrate contains bupropion, hydroxybupropion, flurbiprofen, 4'-hydroxyflurbiprofen, omeprazole, 5'- hydroxyomeprazole)

Maximum observed plasma concentration (Cmax)
Up to Day 23
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))
Up to Day 23
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF))
Up to Day 23
Time of maximum observed plasma concentration (Tmax)
Days 1 to 11
Dose limiting toxicities (DLTs) (Phase 1)
Within 28 days of the first repotrectinib dose

Define the dose limiting toxicities (DLTs) (Phase 1)

Pediatric Recommended Phase 2 Dose (RP2D) (Phase 1)
Within 28 days of the last patient dosed in escalation

To determine the pediatric RP2D (Phase 1)

Overall Response Rate (ORR) (Phase 2)
Two to three years after first dose of repotrectinib

To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (Phase 2)

Recommended Phase 2 Dose (RP2D) (Phase 1)
Within 28 days of the last patient dosed in escalation

To determine the RP2D (Phase 1)

Overall Response Rate (ORR) Phase 2
Two to three years after first dose of repotrectinib dose

To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (Phase 2)

Secondary Endpoints

Overall Survival (OS)
Up to approximately 41 months
Overall Response Rate (ORR) as per BICR according to RECIST v1.1
Up to approximately 41 months
ORR as per Investigator according to RECIST v1.1
Up to approximately 41 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm AEXPERIMENTAL -
Arm BACTIVE_COMPARATOR -
Cohort 1EXPERIMENTAL -
Cohort 2EXPERIMENTAL -
Part 1EXPERIMENTAL -
Part 2EXPERIMENTAL -
Group 1: Moderate Hepatic ImpairmentEXPERIMENTAL -
Group 2: Severe Hepatic ImpairmentEXPERIMENTAL -
Group 3: Normal Hepatic FunctionEXPERIMENTAL -
Repotrectinib (TPX-0005)EXPERIMENTALPhase 1 Oral repotrectinib (TPX-0005): Safety and tolerability at different dose levels Phase 2 Oral repotrectinib (TPX-0005): 3 cohorts Cohort 1: TKI-naive NTRK fusion Cohort 2: Prior TKI NTRK fusion Cohort 3: ROS1 gene fusions or other ROS1 aberrations

Interventions

NameTypeDescription
RepotrectinibDRUGSpecified dose on specified days
CrizotinibDRUGSpecified dose on specified days
MetforminDRUGSpecified dose on specified days
DigoxinDRUGSpecified dose on specified days
RosuvastatinDRUGSpecified dose on specified days
BupropionDRUGSpecified dose on specified days
FlurbiprofenDRUGSpecified dose on specified days
OmeprazoleDRUGSpecified dose on specified days
VoriconazoleDRUGSpecified dose on specified days
QuinidineDRUGSpecified dose on specified days
Oral repotrectinib (TPX-0005)DRUGOral repotrectinib (TPX-0005)
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites122

Inclusion Criteria: * Participant has histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC * Participant has a ROS1 gene rearrangement/fusion as detected by a local test. * At least 1 measurable lesion according to RECIST v1.1, as assessed by the investigator....

Countries:United StatesArgentinaAustriaBrazilCanadaChileChinaFranceGermanyGreeceHungaryIndiaItalyJapanNetherlandsPolandRomaniaSouth KoreaSpainSwitzerlandTurkey (Türkiye)AustraliaDenmarkSingaporeTaiwanUnited KingdomBelgiumHong Kong
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Recent Changes (Last 90 Days)

LOWSep 4, 2026NCT04094610lastUpdatePostDate: changed

Frequently asked questions about Repotrectinib

What is repotrectinib used for?

Repotrectinib is an investigational small molecule kinase inhibitor being studied in oncology. It is being evaluated in clinical trials for locally advanced solid tumors, metastatic solid tumors, non-small cell lung cancer, lymphoma, primary CNS tumors, and hepatic impairment. It is also studied in healthy volunteers for pharmacokinetic assessment.

What does repotrectinib target?

Repotrectinib is a kinase inhibitor, belonging to the -tinib class of drugs. It is being studied in patients with tumors harboring ALK, ROS1, or NTRK1-3 rearrangements or alterations, indicating it targets these kinase pathways. The drug is designed to interfere with signaling driven by these genetic alterations.

Who makes repotrectinib?

Repotrectinib is being developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The company is conducting clinical trials to evaluate the drug's safety and efficacy across multiple oncology indications, including non-small cell lung cancer and various solid tumors.

What phase is repotrectinib in?

Repotrectinib is in Phase 3 clinical development. It is being studied in a Phase 3 trial for ROS1-positive non-small cell lung cancer, while additional Phase 1 trials are ongoing for other indications. Repotrectinib is investigational and not yet approved by regulatory authorities.

What clinical trials is repotrectinib in?

Repotrectinib is being studied in several clinical trials. NCT03093116 is a Phase 1 trial in advanced solid tumors with ALK, ROS1, or NTRK1-3 rearrangements. NCT04094610 is a Phase 1 pediatric trial. NCT06140836 is the Phase 3 TRIDENT-3 trial versus crizotinib in NSCLC. NCT06352528 is a completed Phase 1 hepatic impairment study.

Is repotrectinib the same as TPX-0005?

Yes, repotrectinib is also known as oral repotrectinib (TPX-0005). The drug is referred to by both names in clinical trial documentation, and TPX-0005 is the earlier development code. Researchers and investors may encounter either name when reviewing study data.