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

Advanced or Metastatic Solid Tumors Clinical Trial

— SEACRAFT-1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05907304
• Other study ID #: ERAS-254-01
• Status: Recruiting
• Phase: Phase 1
• Start date: August 17, 2023
• Est. completion date: November 2025

Study information

• Verified date: June 2024
• Source: Erasca, Inc.
• Contact: Erasca Clinical Team
• Phone: 1-858-465-6511
• Email: clinicaltrials[@]erasca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 115
• Est. completion date: November 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 99 Years

Eligibility

Key Inclusion Criteria:

1. Willing and able to provide written informed consent

2. Age = 12 years

3. 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.

4. 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.

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. ECOG performance status 0, 1 or 2

7. Presence of at least 1 measurable lesion according to RECIST v1.1

8. Able to swallow oral medication.

Exclusion Criteria:

1. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor

2. 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)

3. 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)

4. 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

5. LVEF <50%

6. All primary CNS tumors

7. Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.

8. 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;

9. Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors

Intervention

Drug:
• Naporafenib
Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor
• Trametinib
Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.

Locations

Country	Name	City	State
Australia	Macquarie University	Macquarie Park	New South Wales
Australia	St. Vincent's Hospital	Melbourne	Victoria
Australia	Linear Clinical Research, LTD	Perth
Canada	London Regional Cancer Center	London	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan	Busan Gwang'yeogsi
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Hospital Bundang	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University Hospital	Seoul
United Kingdom	Sarah Cannon Research Institute - HCA Healthcare	City Of London	London
United Kingdom	Beatson West of Scotland Cancer Center	Glasgow
United States	Emory University School of Medicine	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	Henry Ford Health System	Detroit	Michigan
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	NEXT Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Comprehensive Cancer Center of Nevada (CCCN)	Las Vegas	Nevada
United States	University of Wisconsin	Madison	Wisconsin
United States	SCRI Oncology Partners (formerly Tennessee Oncology)	Nashville	Tennessee
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Florida Cancer Specialists - St. Petersburg	Saint Petersburg	Florida
United States	University of California, San Francisco	San Francisco	California
United States	Florida Cancer Specialists - Sarasota	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Erasca, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of Response (DOR) for CNS disease in participants	Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)	Assessed up to 24 months from time of first dose
Other	Overall Response Rate (ORR) for CNS disease in participants	Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)	Assessed up to 24 months from time of first dose
Other	Disease Control Rate (DCR) for CNS disease in participants	Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)	Assessed up to 24 months from time of first dose
Other	Pharmacodynamic assessment	DUSP6: changes from baseline in the expression of DUSP-6 mRNA in blood, a marker of MAPK pathway Inhibition.	Assessed up to 24 months from time of first dose
Primary	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	Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
Secondary	Duration of Response (DOR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Time to Response (TTR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Progression Free Survival (PFS)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Disease Control Rate (DCR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Plasma concentration (Cmax)	Maximum plasma concentration of ERAS-254 and trametinib	Study Day 1 up to Day 29
Secondary	Time to achieve Cmax (Tmax)	Time to achieve maximum plasma concentration of ERAS-254 and trametinib	Study Day 1 up to Day 29
Secondary	Area under the curve (AUC)	Area under the plasma concentration-time curve	Study Day 1 up to Day 29
Secondary	Overall survival	Survival Status	Assessed up to 24 months from time of first dose