NCT06610682

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

A Trial to Evaluate Deoxyribonucleic) in BRAF (V-raf Murine Sarcoma Viral Oncogene Homolog B1)-Altered Glioma During Treatment With Plixorafenib Alone or With Retifanlimab

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This clinical trial is designed as a pilot, signal-finding study to demonstrate the feasibility of detecting ctDNA at C1D1 (baseline) and pre-C2 (week 4) (primary endpoint), as well as correlating with disease status as per radiographic response (RR; secondary endpoint). In addition, the investigators will generate preliminary data for the activity of plixorafenib co-administered with retifanlimab in this heavily-pretreated population. Patients with measurable (by RANO 2.0), recurrent BRAF-V600E mutant glioma will be screened and consented for the study prior to surgery. Patients will undergo pre-operative MRI and clinically-indicated resection or biopsy (specific approach as per treating neurosurgeon) for confirmation of progression and characterization of potential acquired resistance alterations. All patients will have a ventricular reservoir placed at time of surgery with CSF and plasma sampling. Arm A: Patients will start the study drug (plixorafenib 900mg daily 30 minutes after a full meal or meal supplement) 7-28 days post-operatively, when clinically stable. Patients will take the drug daily by mouth continuously for 28-day cycles until progressive disease or up to 24 cycles. MRI will be performed post-operatively (between surgery and start of study drug) for evaluation of measurable disease, at the beginning of Cycle 2, then at the beginning of every odd cycle. Blood and CSF samples will be obtained on day of surgery, C1D1 (baseline), pre-C2 (week 4) and with every odd cycle up to and including C7 and EOT. Arm B: This arm will evaluate the safety and biological effect of plixorafenib in combination with retifanlimab. Participants will receive one dose of retifanlimab prior to surgery. Following surgery, the participants will start plixorafenib 7-28 days post-operatively, when clinically stable. Retifanlimab (administered by IV every 28 days) will be restarted after one cycle of plixorafenib or after the 2nd cycle of plixorafenib per physician discretion. Patients will take the drugs in 28-day cycles until progressive disease or up to 24 cycles. MRI, blood, CSF and other study assessments will be performed as for Arm A.

Conditions

• BRAF V600E Mutation

Interventions

Type	Name	Description
DRUG	Plixorafenib	Patients will start the study drug (plixorafenib 900mg daily 30 minutes after a full meal or meal supplement) 7-28 days post-operatively, when clinically stable. Patients will take the drug daily by mouth continuously for 28-day cycles until progressive disease or up to 24 cycles. MRI will be performed post-operatively (between surgery and start of study drug) for evaluation of measurable disease, at the beginning of Cycle 2, then at the beginning of every odd cycle. Blood and CSF samples will be obtained on day of surgery, C1D1 (baseline), pre-C2 (week 4) and with every odd cycle up to and including C7 and EOT.
DRUG	Retifanlimab	Investigators will evaluate the sensitivity of ctDNA from plasma and CSF at baseline 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.

Timeline

• Start date: 2025-04-07
• Primary completion: 2027-06-30
• Completion: 2028-06-30
• First posted: 2024-09-24
• Last updated: 2026-04-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study