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

NCT ID: NCT06346067

Last Updated: 2025-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

470 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-29

Study Completion Date

2028-12-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Advanced or Metastatic NRAS-mutant Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stage 1 Dose selection Lead-in Arm 1

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

Group Type EXPERIMENTAL

Naporafenib

Intervention Type DRUG

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

Trametinib

Intervention Type DRUG

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

Stage 1 Dose selection Lead-in Arm 2

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

Group Type EXPERIMENTAL

Naporafenib

Intervention Type DRUG

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

Trametinib

Intervention Type DRUG

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

Stage 1 Dose selection Lead-in Arm 3 Trametinib monotherapy

Trametinib 2 mg once daily (QD)

Group Type ACTIVE_COMPARATOR

Trametinib

Intervention Type DRUG

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

Stage 2 Arm A

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

Group Type EXPERIMENTAL

Naporafenib

Intervention Type DRUG

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

Trametinib

Intervention Type DRUG

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

Stage 2 Arm B - Physician's Choice

* 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

Group Type ACTIVE_COMPARATOR

Dacarbazine

Intervention Type DRUG

Dacarbazine IV - Day 1

Temozolomide

Intervention Type DRUG

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

Trametinib

Intervention Type DRUG

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

Interventions

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Naporafenib

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

Intervention Type DRUG

Dacarbazine

Dacarbazine IV - Day 1

Intervention Type DRUG

Temozolomide

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

Intervention Type DRUG

Trametinib

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

Intervention Type DRUG

Other Intervention Names

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ERAS-254 LXH254 DTIC Temodar TMZ Mekinist

Eligibility Criteria

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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 drug(s) as determined locally with an analytically validated assay in a certified testing laboratory.
5. Archival tumor tissue collected within 5 years prior to enrollment must be confirmed to be available at the time of Screening, which may be submitted before or after enrollment for exploratory biomarker analysis.
6. Must have received an anti-PD-1/L1 based regimen (monotherapy or combination). Patient must have documented disease progression either while receiving therapy or within 12 weeks of last dose of the most recent anti-PD-1/L1 based regimen; the patient is eligible if they have received other therapies between the most recent anti-PD-1/L1 based regimen and enrollment.
7. ECOG performance status 0, 1 or 2
8. Presence of at least 1 measurable lesion according to RECIST v1.1
9. Able to swallow oral medication.

Exclusion Criteria

1. Patients with uveal or mucosal melanoma
2. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
3. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug(s) (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
4. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndrome)
5. LVEF \<50%
6. Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
7. Patients receiving treatment with herbal medicine known to cause liver toxicity, which cannot be discontinued 7 days prior to first dose of study drug(s) and for the duration of the study.
8. Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Erasca, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joyce Antal

Role: STUDY_DIRECTOR

Clinical Development

Locations

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Mayo Clinic - Arizona

Phoenix, Arizona, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

The Melanoma and Skin Care Institute

Englewood, Colorado, United States

Site Status RECRUITING

Mayo Clinic - Florida

Jacksonville, Florida, United States

Site Status RECRUITING

University of Miami Sylvester Cancer

Miami, Florida, United States

Site Status RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status RECRUITING

Ochsner Clinic Foundation

Jefferson, Louisiana, United States

Site Status ACTIVE_NOT_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status RECRUITING

SCRI Oncology Partners (formerly Tennessee Oncology)

Nashville, Tennessee, United States

Site Status RECRUITING

Texas Oncology- Austin Midtown

Austin, Texas, United States

Site Status RECRUITING

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

The University of Utah - Huntsman Cancer Institute (HCI)

Salt Lake City, Utah, United States

Site Status RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

University of Wisconsin

Madison, Wisconsin, United States

Site Status RECRUITING

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Site Status RECRUITING

Tasman Health Care

Southport, Queensland, Australia

Site Status RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status RECRUITING

Peter MacCallum Cancer Institute

Melbourne, Victoria, Australia

Site Status RECRUITING

Hollywood Private Hospital

Nedlands, Western Australia, Australia

Site Status RECRUITING

Alfred Hospital

Melbourne, , Australia

Site Status RECRUITING

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

Site Status RECRUITING

Masarykuv Onkologicky Ustav-MOU

Brno, , Czechia

Site Status RECRUITING

Fakultni nemocnice Hradec Kralove

Nový Hradec Králové, , Czechia

Site Status RECRUITING

Sanatorium Profesora Arenbergera

Prague, , Czechia

Site Status RECRUITING

Centre Hospitalier Universitaire (CHU) de Bordeaux - Hospitalier Saint-Andre

Bordeaux, , France

Site Status RECRUITING

CHU Dijon Bourgogne - Hopital Francois Mitterand (Hopital du Bocage)

Dijon, , France

Site Status RECRUITING

Centre Hospitalier du Mans

Le Mans, , France

Site Status RECRUITING

CHRU de Lille - Hôpital Claude Huriez

Lille, , France

Site Status RECRUITING

Centre Hospitalier Lyon-Sud

Lyon, , France

Site Status RECRUITING

Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital de la Timone

Marseille, , France

Site Status RECRUITING

Hospital Ambroise Pairs

Paris, , France

Site Status RECRUITING

APHP - Hopital Saint Louis

Paris, , France

Site Status RECRUITING

CLCC Institute Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele (HSR) (Istituto Scientifico Universitario Sa

Milan, , Italy

Site Status RECRUITING

IRCCS Istituto Nazionale Tumori Regina Elena

Roma, , Italy

Site Status RECRUITING

Istituto Dermopatico dell Immacolata IDI-IRCCS

Roma, , Italy

Site Status RECRUITING

Azienda Sanitaria Universitaria del Friuli Centrale

Udine, , Italy

Site Status RECRUITING

Isala Ziekenhuis

Amsterdam, , Netherlands

Site Status RECRUITING

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Site Status RECRUITING

Radboud University

Nijmegen, , Netherlands

Site Status RECRUITING

Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)

Barcelona, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital HM Sanchinarro

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Central de Asturias

Oviedo, , Spain

Site Status ACTIVE_NOT_RECRUITING

Royal Preston Hospital

Preston, Lancashire, United Kingdom

Site Status RECRUITING

Sarah Cannon Research Institute - HCA Healthcare

City of London, London, United Kingdom

Site Status RECRUITING

Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Site Status RECRUITING

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Christie Hospital

Manchester, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Australia Canada Czechia France Italy Netherlands Spain United Kingdom

Central Contacts

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Erasca Clinical Team

Role: CONTACT

1-858-465-6511

Other Identifiers

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ERAS-254-02

Identifier Type: -

Identifier Source: org_study_id

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