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Naporafenib

Phase 3

Advanced or Metastatic NRAS-mutant Melanoma | Small molecule | Oncology |Erasca, Inc.|Last Updated: Feb 27, 2026

Target and mechanism

Molecular targetRAF1, BRAF
Target classInhibitor
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment78

FDA Designations

FAST_TRACK

Clinical trial landscape

Naporafenib · 2 trials · 2 indications

Phase 3 1Phase 1 1
NCT06346067A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)Advanced or Metastatic NRAS-mutant Melanoma
ACTIVE NOT_RECRUITING78 Analytics
PHASE3ACTIVE NOT_RECRUITING
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)
Advanced or Metastatic NRAS-mutant MelanomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2
Assessed up to 6 months from time of first dose

Incidence and severity of treatment-emergent AEs and serious AEs

Stage 2: To compare PFS and OS for patients who are randomized to receive the combination of naporafenib + trametinib to that of patients who receive physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy)
Assessed up to 24 months from time of first dose

* Progression free survival (PFS) based on assessment of radiographic imaging per RECIST v1.1 * Survival status

To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors
Assessed up to 24 months from time of first dose

Based on assessment of Objective response rate (ORR) per RECIST version 1.1

Secondary Endpoints

Adverse Events
Assessed up to 24 months from time of first dose
Duration of Response (DOR)
Assessed up to 24 months from time of first dose]
Time to Response (TTR)
Assessed up to 24 months from time of first dose]
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Stage 1 Dose selection Lead-in Arm 1EXPERIMENTALNaporafenib + Trametinib Naporafenib (ERAS-254) 100 mg administered orally twice daily (BID) Trametinib 1 mg once daily (QD)
Stage 1 Dose selection Lead-in Arm 2EXPERIMENTALNaporafenib + Trametinib Naporafenib (ERAS-254) 400 mg administered orally twice daily (BID) Trametinib 0.5 mg once daily (QD)
Stage 1 Dose selection Lead-in Arm 3 Trametinib monotherapyACTIVE_COMPARATORTrametinib 2 mg once daily (QD)
Stage 2 Arm AEXPERIMENTALNaporafenib + Trametinib Naporafenib (ERAS-254) BID oral administration with Trametinib QD at the dose selected in Stage 1
Stage 2 Arm B - Physician's ChoiceACTIVE_COMPARATOR* Dacarbazine 1000 mg/m2 intravenously (IV) on Day 1 of each 21-day cycle OR * Temozolomide 200 mg/m2/day PO on Day 1 to Day 5 of each 28-day cycle OR * Trametinib monotherapy, 2 mg PO QD
Naporafenib + TrametinibEXPERIMENTALNaporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)

Interventions

NameTypeDescription
NaporafenibDRUGNaporafenib (ERAS-254) is an experimental Pan-Raf inhibitor
DacarbazineDRUGDacarbazine IV - Day 1
TemozolomideDRUGTemozolomide 200 mg/m2/day PO on Day 1 to Day 5 of each 28-day cycle
TrametinibDRUGTrametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
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Eligibility Criteria

Age Range18 Years to 99 Years
SexALL
Healthy VolunteersNo
Study Sites59

Key Inclusion Criteria: 1. Willing and able to provide written informed consent 2. Age ≥ 18 years 3. Histologically or cytologically confirmed unresectable or metastatic cutaneous (includes acral) melanoma. 4. Documentation of an NRAS mutation (tumor tissue or blood) prior to first dose of study dr...

Countries:United StatesAustraliaCanadaCzechiaFranceItalyNetherlandsSpainUnited KingdomSouth Korea
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Frequently asked questions about Naporafenib

What is Naporafenib used for?

Naporafenib is an investigational small molecule being developed for advanced or metastatic solid tumors and advanced or metastatic NRAS-mutant melanoma. It is currently in Phase 3 clinical development and has not been approved by the FDA.

What does Naporafenib target?

Naporafenib targets RAF1 and BRAF, which are kinases involved in the RAS signaling pathway. By inhibiting these targets, it aims to disrupt tumor cell growth in cancers with RAS mutations.

Who makes Naporafenib?

Naporafenib is being developed by Erasca, Inc., a biopharmaceutical company traded on NASDAQ under the ticker ERAS.

What phase is Naporafenib in?

Naporafenib is in Phase 3 clinical development for advanced or metastatic NRAS-mutant melanoma. It is also being studied in a Phase 1 trial for advanced or metastatic solid tumors. It is investigational and not yet FDA approved.

What clinical trials is Naporafenib in?

Naporafenib is being studied in two active trials. NCT05907304 is a Phase 1 trial in advanced or metastatic solid tumors with RAS Q61X mutations. NCT06346067, called SEACRAFT-2, is a Phase 3 trial in NRAS-mutant melanoma.

Is Naporafenib the same as ERAS-254?

Yes, Naporafenib is also known as ERAS-254. Both names refer to the same investigational drug being developed by Erasca, Inc.