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

PHASE1RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

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.

Exclusion criteria

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

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Eligibility

Age eligible for study : 12 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2023-08-17

Primary completion: 2025-07-01

Study completion finish: 2025-11-01

Study type

TREATMENT

Phase

PHASE1

Trial ID

NCT05907304

Intervention or treatment

DRUG: Naporafenib

DRUG: Trametinib

Conditions

• Advanced or Metastatic Solid Tumors

Image related to Advanced or Metastatic Solid Tumors

Condition: Advanced or Metastatic Solid Tumors
DRUG: Naporafenib and other drugs
Macquarie Park, New South Wales, Australia and more
Sponsor: Erasca, Inc.

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Find a site

Closest Location:

Macquarie University

Research sites nearby

Select from list below to view details:

Macquarie University
Macquarie Park, New South Wales, Australia
St. Vincent's Hospital
Melbourne, Victoria, Australia
Linear Clinical Research, LTD
Perth, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Naporafenib + Trametinib Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)	DRUG: Naporafenib Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
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
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
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
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
Plasma concentration (Cmax)	Maximum plasma concentration of ERAS-254 and trametinib	Study Day 1 up to Day 29
Time to achieve Cmax (Tmax)	Time to achieve maximum plasma concentration of ERAS-254 and trametinib	Study Day 1 up to Day 29
Area under the curve (AUC)	Area under the plasma concentration-time curve	Study Day 1 up to Day 29
Overall survival	Survival Status	Assessed up to 24 months from time of first dose

Frequently Asked Questions

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References

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