Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Dacarbazine

Trametinib

Naporafenib

Antineoplastic Agents, Alkylating

Alkylating Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Naporafenib + Trametinib Naporafenib (ERAS-254) 100 mg administered orally twice daily (BID) Trametinib 1 mg once daily (QD)

Naporafenib + Trametinib Naporafenib (ERAS-254) 400 mg administered orally twice daily (BID) Trametinib 0.5 mg once daily (QD)

Naporafenib + Trametinib Naporafenib (ERAS-254) BID oral administration with Trametinib QD at the dose selected in Stage 1

* 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 (ERAS-254) is an experimental Pan-Raf inhibitor

Temozolomide 200 mg/m2/day PO on Day 1 to Day 5 of each 28-day cycle

Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.

Erasca Clinical Team

Joyce Antal

Stage 1: To select the optimal dose of naporafenib + trametinib to be studied in Stage 2.

Stage 2: To compare progression free survival (PFS) and overall survival (OS) for patients with NRAS-mutant (NRASm) melanoma who are randomized to receive the combination of naporafenib + trametinib to that of patients who are randomized to physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy).

SEACRAFT-2 is a global, Phase III, open-label, randomized study to assess the efficacy and safety of naporafenib administered with trametinib compared to physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) in patients with unresectable or metastatic NRAS mutant melanoma who have progressed on, or are intolerant to, an anti-programmed death-1 ligand 1 (PD 1/L1)-based regimen. The study will consist of 2 stages: dose optimization in Stage 1 and the Phase 3 portion in Stage 2.

A total of approximately 470 eligible patients will be randomized to receive study drug(s) in this study across 2 stages.

A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)

A Randomized, Open-label Phase III Study in Patients With Previously Treated Unresectable or Metastatic NRAS Mutant Cutaneous Melanoma Comparing the Combination of Naporafenib + Trametinib to Physician's Choice of Therapy (Dacarbazine, Temozolomide or Trametinib Monotherapy) With a Dose Optimization lead-in [SEACRAFT-2]

Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)

Incidence and severity of treatment-emergent AEs and serious AEs

Objective response rate (ORR) based on assessment of radiographic imaging RECIST v1.1

Maximum plasma concentration of ERAS-254 and trametinib

Time to achieve maximum plasma concentration of ERAS-254 and trametinib

Area under the plasma concentration-time curve

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

Based on assessment of radiographic imaging per RECIST version 1.1

Based on the assessment of radiographic imaging per RECIST version 1.1

Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire \[QLQ\]-C30 subscales and PRO CTCAE® symptom items specific to the potential cutaneous toxicities.

Erasca, Inc.

Respiratory Tract (Lung and Bronchial) Diseases

Gland and Hormone Related Diseases

Digestive System Diseases

Carcinoma, Non-Small-Cell Lung

Thyroid Diseases

Lung Neoplasms

Pancreatic Neoplasms

Thyroid Neoplasms

Pancreatic Cancer

Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)

Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor

Joyce Antal, MS

To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors

* To evaluate the safety and tolerability of naporafenib administered with trametinib in patients with RAS Q61X solid tumors
* To characterize the pharmacokinetic (PK) profile of naporafenib and trametinib when administered to patients with RAS Q61X solid tumors

SEACRAFT-1 is an open-label study to assess the safety and efficacy of naporafenib administered with trametinib in previously treated patients with locally advanced unresectable or metastatic RAS Q61X solid tumor malignancies. The study will enroll a total of approximately 100 adult patients; a sub-study will enroll approximately 15 adolescent patients ≥12 and \<18 years for a total sample size of approximately 115. Patients with a locally advanced unresectable or metastatic solid tumor malignancy that is not responsive to standard therapies or for which there is no standard therapy are eligible. Patients with primary central nervous system (CNS) tumors are not eligible. Documentation of a RAS Q61X mutation in tumor tissue prior to the first dose of study treatment is required.

A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations

An Open-label Study to Assess the Safety and Efficacy of Naporafenib (ERAS-254) Administered With Trametinib in Previously Treated Patients With Locally Advanced Unresectable or Metastatic Solid Tumor Malignancies With RAS Q61X Mutations

DUSP6: changes from baseline in the expression of DUSP-6 mRNA in blood, a marker of MAPK pathway Inhibition.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)	NCT06346067	Advanced or Met...	Naporafenib Dacarbazine Temozolomide Trametinib	18 Years - 99 Years	Erasca, Inc.
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)	NCT06346067	Advanced or Met...	Naporafenib Dacarbazine Temozolomide Trametinib	18 Years - 99 Years	Erasca, Inc.
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations	NCT05907304	Advanced or Met...	Naporafenib Trametinib	12 Years - 99 Years	Erasca, Inc.
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations	NCT05907304	Advanced or Met...	Naporafenib Trametinib	12 Years - 99 Years	Erasca, Inc.
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations	NCT05907304	Advanced or Met...	Naporafenib Trametinib	12 Years - 99 Years	Erasca, Inc.

Spots Global Cancer Trial Database for naporafenib

Every month we try and update this database with for naporafenib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for naporafenib

Every month we try and update this database with for naporafenib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for naporafenib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.