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

Recruiting now · Early Phase 1

Conditions studied: BRAF V600E Mutation

In brief

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.

Key facts

Study ID

NCT06610682

Run by

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

People needed

24

Starts

2025-04-07

Expected to finish

2028-06-30

Last updated by the study team

2026-04-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Exclusion Arm A Only:
• Prior RAF dimer disruptor or pan-RAF inhibitor.
• Exclusion Arm B Only:
• 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.
• Exclusion Both Arms:
• 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.
• History of recent (≤ 90 days) thromboembolic or cerebrovascular event such as transient ischemic attack, cerebrovascular accident, or hemodynamically significant (massive or sub-massive) deep vein thrombosis or pulmonary emboli (DVT/PE). Note: Patients with DVT/PE that does not result in hemodynamic instability may enroll as long as the participants are anticoagulated for at least 4 weeks. Note: Patients with DVT/PE related to indwelling catheters or other procedures may enroll.
• Known history of any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus. Subjects with previously treated viral hepatitis and undetectable virus may be eligible.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible.
• Pregnant women are excluded from this study because the effects of plixorafenib or retifanlimab on a fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with plixorafenib, breastfeeding should be discontinued if the mother is treated on study.
• Contraindication to ventricular reservoir placement or biospecimen collection.
• Current use of strong inhibitors or inducers of CYP3A.

Where it is running

• Johns Hopkins — Baltimore, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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