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

NCT06610682 | Recruiting Early Phase 1 DMC FDA Drug

• 3 other identifiers: J2488FoundationIRB00457005
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

BRAF V600E Mutation

Keywords

BRAF,; BRAF V600E mutant; Plixorafenib; Retifanlimab; recurrent

Outcome Measures

Primary Outcomes (1)

• Detection rate of BRAF-V600E ctDNA in CSF and/or plasma

  Proportion of patients with detectable ctDNA in CSF and/or plasma detected at surgery, baseline (C1D1), and pre-Cycle 2 (week 4).

  surgery, baseline (C1D1) and pre-cycle 2 (week 4)

Secondary Outcomes (3)

• Compare BRAF-V600 ctDNA levels in CSF and plasma after treatment among patients with different radiographic responses

  up to 16 weeks

• Radiographic response rate in each arm

  up to 16 weeks

• Percentage of patients with serious Treatment-Emergent Adverse Events (TEAEs) treated with plixorafenib alone or in combination with retifanlimab.

  up to 24 months

Study Arms (2)

Plixorafenib alone (Arm A)

EXPERIMENTAL

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: Plixorafenib

Plixorafenib in combination with retifanlimab (Arm B)

EXPERIMENTAL

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.

Drug: Plixorafenib; Drug: Retifanlimab

Interventions

Plixorafenib DRUG

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.

Plixorafenib alone (Arm A); Plixorafenib in combination with retifanlimab (Arm B)

Retifanlimab DRUG

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.

Plixorafenib in combination with retifanlimab (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Prior RAF dimer disruptor or pan-RAF inhibitor.
• Prior immunotherapy (of note prior RAF dimer-disruptor or pan-RAF inhibitor is allowed).
• Known history of clinically significant autoimmune disease that, in the opinion of the investigator, may be exacerbated by immune checkpoint blockade (e.g., multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease), with the following exceptions: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment (subjects with a history of flares requiring systemic treatment are excluded), or other autoimmune conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Daily systemic steroids \> 4mg daily dexamethasone or equivalent.
• Have received a live vaccine within 28 days before the planned start of study treatment.
• Current use of any other standard or investigational agents (excepting tumor treating fields).
• Known co-occurring NF1 and/or RAS-related alteration known to cause resistance.
• Known hypersensitivity to plixorafenib, retifanlimab or to excipients.
• Current use of a prohibited medication (including herbal medications, supplements, or foods), as described in Section 5.6, or use of a prohibited medication ≤ 7 days prior to first infusion of retifanlimab.
• Impairment in gastrointestinal function or disease that may significantly alter the absorption of oral plixorafenib (such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Clinically significant cardiovascular disease including, but not limited to the following:
• History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary artery bypass grafting, coronary angioplasty or stenting ≤ 180 days prior to start date;
• Congestive heart failure requiring treatment (New York Heart Association Grade \> 2);
• History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
• QTcF interval ≥ 480 ms.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Fore Biotherapeutics: collaborator
• Ivy Brain Tumor Foundation: collaborator
• Incyte Corporation: collaborator

Study Sites (1)

Johns Hopkins

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Karisa Schreck, MD

  Johns Hopkins University

  STUDY CHAIR

Central Study Contacts

Study Chair, MD

CONTACT

410-955-8837; ksolt1@jhmi.edu

Principal Investigator, MD

CONTACT

410-955-8837

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: September 24, 2024
• Study Start: April 7, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)