Actively Recruiting

Early Phase 1
Age: 18Years +
All Genders
NCT06610682

A Trial to Evaluate CSF ctDNA and Safety of Plixorafenib Alone or With Retifanlimab in Patients With BRAF-altered Glioma

Led by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Updated on 2026-04-16

24

Participants Needed

1

Research Sites

168 weeks

Total Duration

On this page

Sponsors

S

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

F

Fore Biotherapeutics

Collaborating Sponsor

AI-Summary

What this Trial Is About

The investigators will evaluate the sensitivity of ctDNA from plasma and CSF at baseline (defined as C1D1) and over time in response to treatment with plixorafenib alone or in combination with retifanlimab in patients with BRAF-V600E mutant glioma refractory to prior therapies.

CONDITIONS

Official Title

A Trial to Evaluate CSF ctDNA and Safety of Plixorafenib Alone or With Retifanlimab in Patients With BRAF-altered Glioma

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patient must have received prior BRAF and/or MEK inhibitor therapy
  • No prior RAF dimer disruptor or pan-RAF inhibitor for Arm A; allowed for Arm B
  • No prior immunotherapy for Arm B; allowed for Arm A
  • Intervals from prior treatments: BRAFi/MEKi stopped 2 weeks before surgery (Arm A) or 7 days before retifanlimab infusion and 2 weeks before surgery (Arm B)
  • Stable or decreasing systemic corticosteroid dose prior to screening MRI
  • Histologic diagnosis of primary CNS tumor with documented BRAF-V600E mutation by CLIA-approved DNA or RNA test
  • Karnofsky performance status of 70 or higher
  • Age 18 years or older
  • Measurable disease by RANO 2.0 on screening MRI; leptomeningeal disease allowed
  • Willing to submit archival tumor sample if available
  • Specified intervals elapsed from prior radiation, anti-VEGF therapy, chemotherapy, and investigational agents
  • Adequate organ and marrow function as defined by specified blood counts and lab values
  • Able to provide written informed consent
  • Resolved adverse events from prior therapies to Grade 1 or baseline, with some exceptions
  • Ability to swallow and retain oral medications
  • Female participants of childbearing potential must have negative pregnancy test and use contraception or abstinence
  • Male participants must be surgically sterile or use contraception
  • No concurrent malignancy except certain treated cancers or disease-free for over 2 years
  • Life expectancy of at least six months
Not Eligible

You will not qualify if you...

  • Prior RAF dimer disruptor or pan-RAF inhibitor (Arm A only)
  • Prior immunotherapy (Arm B only)
  • Significant autoimmune disease that could worsen with immune checkpoint blockade, except certain controlled conditions
  • Daily systemic steroids over 4 mg dexamethasone or equivalent
  • Live vaccine within 28 days before starting treatment
  • Use of other standard or investigational agents, except tumor treating fields
  • Known NF1 or RAS-related alterations causing resistance
  • Known allergy to plixorafenib, retifanlimab, or excipients
  • Use of prohibited medications within 7 days before retifanlimab infusion
  • Gastrointestinal problems affecting absorption of oral plixorafenib
  • Significant cardiovascular disease or recent serious cardiac events
  • Recent thromboembolic or cerebrovascular events, with some exceptions
  • Positive tests for active hepatitis B or C infection
  • Uncontrolled infection or psychiatric/social conditions limiting compliance
  • Pregnant or breastfeeding women
  • Contraindications to ventricular reservoir placement or biospecimen collection
  • Use of strong CYP3A inhibitors or inducers

AI-Screening

AI-Powered Screening

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Trial Site Locations

Total: 1 location

1

Johns Hopkins

Baltimore, Maryland, United States, 21231

Actively Recruiting

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Research Team

S

Study Chair, MD

CONTACT

P

Principal Investigator, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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