What side effects are associated with this type of intervention?

Common side effects of treatments for solid tumors, particularly those involving Pan-RAF inhibitors like naporafenib and MEK inhibitors like trametinib, include skin rash, diarrhea, fatigue, and elevated liver enzymes. MEK inhibitors can also cause hypertension, cardiomyopathy, and ocular toxicity. These side effects are important considerations when evaluating the safety and tolerability of these targeted therapies.

What prior FDA approvals exist?

The FDA has approved several drugs targeting the RAS/RAF/MEK/ERK pathway for the treatment of solid tumors. Notably, trametinib, a MEK inhibitor, is approved for use in combination with dabrafenib, a BRAF inhibitor, for the treatment of BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. This combination has also been approved for BRAF V600E-mutated non-small cell lung cancer and anaplastic thyroid cancer. These approvals highlight the therapeutic potential of targeting the RAF and MEK components of the pathway in solid tumors.

What other types of research exist?

Promising novel alternatives for solid tumor patients include multitargeted kinase inhibitors such as regorafenib, cabozantinib, sorafenib, and lenvatinib. Additionally, immune checkpoint inhibitors like nivolumab and pembrolizumab, either alone or in combination with other agents, are emerging as effective treatments. These therapies target various pathways involved in tumor growth and immune evasion, offering potential benefits for patients with solid tumors.

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Kinase Inhibitor

Naporafenib + Trametinib for Solid Tumors (SEACRAFT-1 Trial)

Phase 1

Recruiting

Research Sponsored by Erasca, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed up to 24 months from time of first dose

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two drugs, naporafenib and trametinib, to treat advanced cancers with a specific mutation (RAS Q61X). It targets patients whose cancers do not respond to standard treatments. The drugs work by blocking signals that cancer cells need to grow. Trametinib is used in treating various cancers.

Who is the study for?

This trial is for patients aged 12 or older with advanced solid tumors containing a specific mutation (RAS Q61X). They must have at least one measurable tumor, be able to take oral medication, and not have standard treatment options available. Patients who've had certain prior treatments or suffer from conditions affecting drug absorption, heart function, or eye health are excluded.

What is being tested?

The study tests the effectiveness and safety of combining two drugs: Naporafenib and Trametinib in treating solid tumors with RAS Q61X mutations. It also aims to understand how these drugs behave in the body when taken together by patients with this genetic alteration.

What are the potential side effects?

While the exact side effects aren't listed here, similar medications often cause digestive issues, skin reactions, changes in blood pressure or heart rhythm, vision problems, fatigue and may affect liver function. The trial will closely monitor participants for any adverse reactions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ assessed up to 24 months from time of first dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~assessed up to 24 months from time of first dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and assessed up to 24 months from time of first dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

Adverse Events

Area under the curve (AUC)

Disease Control Rate (DCR)

+6 more

Other study objectives

Disease Control Rate (DCR) for CNS disease in participants

Duration of Response (DOR) for CNS disease in participants

Overall Response Rate (ORR) for CNS disease in participants

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Naporafenib + TrametinibExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trametinib

2014

Completed Phase 2

~1630

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Naporafenib and trametinib are targeted therapies used in the treatment of solid tumors with specific genetic mutations. Naporafenib is a Pan-RAF inhibitor that blocks RAF proteins, which are part of the RAS-RAF-MEK-ERK signaling pathway involved in cell division and survival. Trametinib is a MEK inhibitor that targets MEK proteins in the same pathway. By inhibiting these proteins, these drugs can reduce tumor growth and promote cancer cell death. This is particularly important for patients with solid tumors harboring RAS mutations, as these targeted therapies can offer a more effective and personalized treatment approach compared to traditional chemotherapy.