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BRAF V600E MutationEarly Phase 1NCT06610682

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

A Early Phase 1 study testing Plixorafenib and Retifanlimab in people with BRAF V600E Mutation, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
BRAF V600E Mutation
What is being tested?
Plixorafenib and Retifanlimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
2 sitesUnited States
Study dates
7 Apr 2025to 30 Jun 2028
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must have received prior BRAF and/or MEK inhibitor therapy.
  • Prior RAF dimer disruptor or pan-RAF inhibitor not allowed
  • Prior immunotherapy allowed
  • The following intervals from previous treatments should have elapsed prior to enrollment:
  • BRAFi/MEKi should be stopped 2 weeks prior to surgery
  • Patients must be maintained on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to screening MRI. No maximum dose. Topical and inhaled steroid treatment is allowed.
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  • Patient must have received prior BRAF and/or MEK inhibitor therapy.
  • Prior RAF dimer disruptor or pan-RAF inhibitor allowed,
  • Prior immunotherapy not allowed (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathway).
  • The following intervals from previous treatments should have elapsed prior to first infusion:
  • BRAFi/MEKi should be stopped 7 days prior to first retifanlimab infusion and at least 2 weeks prior to surgery.
  • Patients must be maintained on a stable (<4mg daily dexamethasone) or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to screening MRI. Topical and inhaled steroid treatment is allowed.
  • Histologic diagnosis of a primary CNS tumor with documented BRAF-V600E mutation by a CLIA approved DNA or RNA-based sequencing test (NGS or RNAseq). Immunohistochemistry alone is insufficient.
  • Karnofsky performance status ≥ 70.
  • Patient is 18 years of age or older.
  • Measurable disease by RANO 2.0 criteria on screening MRI. Leptomeningeal disease allowed.
  • Willing to submit archival tumor sample if available.
  • The following intervals from previous treatments should have elapsed prior to either day of surgery (for Arm A) or first infusion of Retifanlimab (for Arm B):
  • 12 weeks from the completion of radiation.
  • 8 weeks from an anti-VEGF therapy
  • 4 weeks from a nitrosourea chemotherapy
  • 2 weeks or 5 half-lives from any investigational (not FDA-approved) agents or FDA-approved non-nitrosourea chemotherapy (whichever is shorter)
  • Patients must have the following organ and marrow function:
  • Absolute neutrophil count >1,000/mcL
  • Platelets >100,000/mcL
  • Hemoglobin > 9 g/dL
  • Total bilirubin < 1.5 x institutional upper limit of normal (ULN) OR total bilirubin >1.5 × ULN with direct bilirubin < 1.5 × ULN;
  • AST (SGOT) and ALT (SGPT) < 2.5 x institutional ULN
  • PT or PTT < 1.5 x institutional ULN
  • Creatinine ≤ 1.5 x institutional ULN OR
  • Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
  • Patient must be able to provide written informed consent.
  • All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline except for
  • Alopecia (Grade ≤2)
  • Sensory neuropathy (Grade ≤2)
  • Lymphopenia (Grade <2)
  • Other adverse events that have resolved to Grade ≤2 that, according to the clinical judgment of the investigator, do not constitute a safety risk to the participant.
  • Ability to swallow and retain orally administered medications, including a liquid suspension.
  • Female participants of childbearing potential (defined as all females who have experienced menarche and who are not postmenopausal or surgically sterile) must have a negative serum pregnancy test prior to study start. Surgical sterility (methods inclusive of hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or post-menopausal state (amenorrhea for ≥24 months without an alternative medical cause and FSH ≥30 mIU/mL) must be confirmed. Female participants of childbearing potential must agree to use highly effective contraception or practice true abstinence (defined as refraining from heterosexual intercourse during the entire specified period) and not to donate ova from screening through 30 days after the last dose of plixorafenib or 120 days after last dose of retifanlimab. Highly effective contraception is defined as 1) intrauterine device, 2) abstinence, or 3) combined estrogen and progesterone or progesterone only containing implants, injectables, transdermal, or intravaginal contraceptives.
  • Male participants must also be documented to be surgically sterile or agree to use adequate contraception and not to donate sperm from screening until 30 days after the last dose of plixorafenib or 120 days after last dose of retifanlimab.
  • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with other malignancies must be disease-free for > 2 years.
  • Life expectancy equal or greater than six months.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Study Chair, MD contact

410-955-8837

ksolt1@jhmi.edu

Principal Investigator, MD contact

410-955-8837

United States2 sites, 2 recruiting

  • Johns Hopkins

    Baltimore, Maryland, 21231

    Karisa Schreck, MD, 410-955-8837

    Recruiting

  • NYU Langone Health Perlmutter Cancer Center Ambulatory Care Center

    New York, New York, 10016

    Research Nurse, RN, 212-731-6267

    Not yet recruiting

Other trials in United States

About this study

Official title: 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

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.

Read the 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.

Being tested
Plixorafenib, Retifanlimab
Keywords
BRAF,, BRAF V600E mutant, Plixorafenib, Retifanlimab, recurrent
Medical subject headings
Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlixorafenibDrug

    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.

  • RetifanlimabDrug

    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.

Study groups in NCT06610682
Study groupRoleWhat they receive
Plixorafenib alone (Arm A)ExperimentalPatients 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
Receives: Drug: Plixorafenib
Plixorafenib in combination with retifanlimab (Arm B)ExperimentalParticipants 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.
Receives: Drug: Plixorafenib; Drug: Retifanlimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

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

Secondary outcomes (3)

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

    Quantify disease progression and treatment response rate over time BRAF-V600 ctDNA levels among patients with different radiographic responses (1="improved", 2="stable", 3="worsened" measured by RANO 2.0 criteria) at 4 and 16 weeks after the treatment initiation (pre-C2, pre-C5). Correlation of ctDNA levels in CSF and plasma samples at baseline, after 4 weeks (pre-C2) and 16weeks of treatment with radiographic disease status after 4 (pre-C2) and 16 weeks (pre-C5) of treatment

    Measured: up to 16 weeks

  2. Radiographic response rate in each arm

    Arm A: Radiographic response by RANO 2.0 criteria at 4 and 16 weeks (pre-C2 \& pre-C5).

    Arm B: Radiographic response by iRANO criteria at 4 and 16 weeks pre-C2 \& pre-C5).

    Measured: up to 16 weeks

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

    CTCAE v5 will be utilized to determine serious TEAEs as outline in the study

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Sep 2024
  2. Study start7 Apr 2025
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06610682
Sponsor's protocol ID
J2488
Other IDs
IRB00457005, 146958
Status last verified
Sep 2026
First submitted
20 Sep 2024
Last updated
22 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Plixorafenib and Retifanlimab in people with BRAF V600E Mutation, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Study Chair, MD (410-955-8837, ksolt1@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Detection rate of BRAF-V600E ctDNA in CSF and/or plasma (time frame: surgery, baseline (C1D1) and pre-cycle 2 (week 4)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06610682.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.

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