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

NCT05907304 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ERAS-254-01
• Study Type: interventional
• Target: 86
• Locations: 5 countries
• Sites: 29

Brief Summary

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

Conditions

Advanced or Metastatic Solid Tumors

Keywords

Melanoma; Non-small cell lung cancer; Thyroid cancer; Colorectal Cancer (cohort full); Pancreatic Cancer; Other solid tumors harboring a RAS Q61X mutation

Outcome Measures

Primary Outcomes (1)

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

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

  Assessed up to 24 months from time of first dose

Secondary Outcomes (9)

• 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

• Progression Free Survival (PFS)

  Assessed up to 24 months from time of first dose

• Disease Control Rate (DCR)

  Assessed up to 24 months from time of first dose

Other Outcomes (4)

• Duration of Response (DOR) for CNS disease in participants

  Assessed up to 24 months from time of first dose

• Overall Response Rate (ORR) for CNS disease in participants

  Assessed up to 24 months from time of first dose

• Disease Control Rate (DCR) for CNS disease in participants

  Assessed up to 24 months from time of first dose

Study Arms (1)

Naporafenib + Trametinib

EXPERIMENTAL

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

Drug: Naporafenib; Drug: Trametinib

Interventions

Naporafenib DRUG

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

Also known as: LXH254, ERAS-254

Naporafenib + Trametinib

Trametinib DRUG

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

Also known as: Mekinist

Naporafenib + Trametinib

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Age ≥ 12 years
• A locally advanced or metastatic tumor who has progressed on or for which no standard therapy exists. Patients who are intolerant to standard therapy or who are not a candidate for standard therapy (in the opinion of the Investigator) or who decline standard therapy are also eligible.
• Documentation of a RAS Q61X mutation (tumor tissue or blood) prior to first dose of study treatment as determined locally with an analytically validated assay in a certified testing laboratory.
• 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.
• ECOG performance status 0, 1 or 2
• Presence of at least 1 measurable lesion according to RECIST v1.1
• Able to swallow oral medication.

You may not qualify if:

• Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
• Impairment of GI function or gastrointestinal (GI) disease that may significantly alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
• 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)
• Corrected QT interval using Fridericia's formula (QTcF) at Screening \>450 ms based on triplicate average NOTE: criterion does not apply to patients with a right or left bundle branch block
• LVEF \<50%
• All primary CNS tumors
• Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
• Patients receiving treatment with medications that are known to be strong inhibitors and/or inducers of cytochrome P450 (CYP)3A; substrates of CYP2C8, CYP2C9, and CYP3A with a narrow therapeutic index and sensitive substrates of CYP3A;
• Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial

Sponsors & Collaborators

• Erasca, Inc.: lead

Study Sites (29)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Florida Cancer Specialists - Sarasota

Sarasota, Florida, 34232, United States

Location

Florida Cancer Specialists - St. Petersburg

St. Petersburg, Florida, 33705, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Center of Nevada (CCCN)

Las Vegas, Nevada, 89169, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

SCRI Oncology Partners (formerly Tennessee Oncology)

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Macquarie University

Macquarie Park, New South Wales, Australia

Location

St. Vincent's Hospital

Melbourne, Victoria, Australia

Location

Linear Clinical Research, LTD

Perth, Australia

Location

Cross Cancer Institute- Alberta Health Services (AHS)

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

London Regional Cancer Center

London, Ontario, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Inje University Haeundae Paik Hospital

Busan, Busan Gwang'yeogsi, 48108, South Korea

Location

Samsung Medical Center

Seoul, Seoul Teugbyeolsi, 06351, South Korea

Location

National Cancer Center

Goyang-si, South Korea

Location

Seoul National University Hospital Bundang

Gyeonggi-do, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

The Catholic University Hospital

Seoul, South Korea

Location

Sarah Cannon Research Institute - HCA Healthcare

City of London, London, W1G 6AD, United Kingdom

Location

Beatson West of Scotland Cancer Center

Glasgow, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms

Interventions

naporafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pancreatic Diseases

Study Officials

• Joyce Antal, MS

  Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2023
• First Posted: June 18, 2023
• Study Start: August 17, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); US (14); AU (3); KR (6); CA (4)