A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations (SEACRAFT-1)
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| ClinicalTrials.gov Identifier: NCT05907304 |
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Recruitment Status :
Recruiting
First Posted : June 18, 2023
Last Update Posted : May 13, 2024
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Sponsor:
Erasca, Inc.
Information provided by (Responsible Party):
Erasca, Inc.
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced or Metastatic Solid Tumors | Drug: Naporafenib Drug: Trametinib | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 115 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | August 17, 2023 |
| Estimated Primary Completion Date : | July 2025 |
| Estimated Study Completion Date : | November 2025 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Trametinib
| Arm | Intervention/treatment |
|---|---|
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Experimental: Naporafenib + Trametinib
Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)
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Drug: Naporafenib
Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor
Other Names:
Drug: Trametinib Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
Other Name: Mekinist |
Primary Outcome Measures :
- To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of Objective response rate (ORR) per RECIST version 1.1
Secondary Outcome Measures :
- Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]Incidence and severity of treatment-emergent AEs and serious AEs
- Duration of Response (DOR) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1
- Time to Response (TTR) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1
- Progression Free Survival (PFS) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1
- Disease Control Rate (DCR) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1
- Plasma concentration (Cmax) [ Time Frame: Study Day 1 up to Day 29 ]Maximum plasma concentration of ERAS-254 and trametinib
- Time to achieve Cmax (Tmax) [ Time Frame: Study Day 1 up to Day 29 ]Time to achieve maximum plasma concentration of ERAS-254 and trametinib
- Area under the curve (AUC) [ Time Frame: Study Day 1 up to Day 29 ]Area under the plasma concentration-time curve
- Overall survival [ Time Frame: Assessed up to 24 months from time of first dose ]Survival Status
Other Outcome Measures:
- Duration of Response (DOR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- Overall Response Rate (ORR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- Disease Control Rate (DCR) for CNS disease in participants [ Time Frame: Assessed up to 24 months from time of first dose ]Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM)
- Pharmacodynamic assessment [ Time Frame: Assessed up to 24 months from time of first dose ]DUSP6: changes from baseline in the expression of DUSP-6 mRNA in blood, a marker of MAPK pathway Inhibition.
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| Ages Eligible for Study: | 12 Years to 99 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05907304
Contacts
| Contact: Erasca Clinical Team | 1-858-465-6511 | clinicaltrials@erasca.com |
Locations
Show 31 study locations
Sponsors and Collaborators
Erasca, Inc.
Investigators
| Study Director: | Joyce Antal, MS | Clinical Development |
| Responsible Party: | Erasca, Inc. |
| ClinicalTrials.gov Identifier: | NCT05907304 |
| Other Study ID Numbers: |
ERAS-254-01 |
| First Posted: | June 18, 2023 Key Record Dates |
| Last Update Posted: | May 13, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Erasca, Inc.:
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Melanoma Non-small cell lung cancer Thyroid cancer |
Colorectal Cancer (cohort full) Pancreatic Cancer Other solid tumors harboring a RAS Q61X mutation |
Additional relevant MeSH terms:
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Trametinib Naporafenib Antineoplastic Agents |
Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |