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Olfactory NeuroblastomaPhase 2NCT05012098

Phase 2 Study of Bintrafusp Alfa in Recurrent/Metastatic Olfactory Neuroblastoma (BARON).

A Phase 2 study testing Bintrafusp alfa/M7824, Ibuprofen and PET scan in people with Olfactory Neuroblastoma and Esthesioneuroblastoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Background: Olfactory neuroblastoma (ONB) is a rare cancer of the nasal cavity. At diagnosis, it is usually locally advanced. It tends to spread to the neck. Sometimes it spreads to the lungs and bones. Researchers want to find a better way to treat it. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bintrafusp alfa/M7824, Ibuprofen and PET scan
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
21 Jun 2022to 9 Jul 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

None listed.

Who cannot join

  • Anticancer treatment, concurrent or prior (chemotherapy, monoclonal antibody, cytokine therapy, immune therapy, targeted small molecule therapy) or any investigational drug, within 4 weeks or 5 half-lives (whichever shorter) prior to the first drug administration. All residual treatment-related toxicities must have resolved or be minimal and not constitute a safety risk. Note: Palliative radiotherapy is permitted concurrently or within the pretreatment period. Subjects receiving bisphosphonates or denosumab are eligible provided treatment was initiated at least 14 days before treatment.
  • Participants who received prior checkpoint blockade therapy and were taken off treatment for serious adverse events related to immuno-therapy are excluded.
  • Major surgery within 4 weeks prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted).
  • Active or prior documented autoimmune or inflammatory diseases that might deteriorate on immunostimulatory agent (including colitis or Crohn's disease, systemic lupus erythematosus, sarcoidosis, vasculitis, Grave's disease, hypophysitis, uveitis, rheumatoid arthritis etc.), except the following:
  • Type I diabetes mellitus
  • Chronic skin conditions that do not require systemic therapy (including eczema, vitiligo, alopecia, psoriasis)
Show all 29Show fewer
  • Hypothyroidism (e.g., post-Hashimoto thyroiditis) stable, on hormone replacement
  • Mild autoimmune disease not active in the last 5 years may be eligible after consultation with the principal investigator.
  • Current use of immunosuppressive medication within 14 days before the first dose of the study medication, except the following:
  • Intranasal, inhaled, topical glucocorticoids; locally injected glucocorticoids (i.e. intra-articular, intra-ocular)
  • Systemic glucocorticoids at physiologic doses (generally <= 10 mg prednisone or equivalent per day)
  • Glucocorticoids as premedication for contrast-enhanced studies is allowed prior to enrollment and on study.
  • Uncontrolled intercurrent chronic or acute illness including, but not limited to the following, that may limit interpretation of results or increase risk to the participant in the judgment of the investigator:
  • Bleeding diathesis or recent (<3 months) clinically significant bleeding event.
  • Prior organ transplantation including allogenic stem-cell transplantation
  • Impaired cardiovascular function or clinically significant cardiovascular disease, including, but not limited to, any of the following:
  • cerebral vascular accident/stroke (< 3 months prior to enrollment),
  • acute coronary syndromes (including myocardial infarction < 6 months prior to enrollment, unstable angina),
  • Congestive Heart Failure (>= New York Heart Association Classification Class III); CHF Class II must have been stable for 3 months prior to enrollment
  • history or presence of clinically significant cardiac arrhythmia including resting bradycardia, uncontrolled atrial fibrillation or paroxysmal supraventricular tachycardia (controlled arrhythmias, e.g., stable atrial fibrillation, may be allowed at the discretion of the investigator),
  • history of myocarditis
  • History of idiopathic pulmonary fibrosis, drug-induced or idiopathic pneumonitis, active interstitial lung disease, blood oxygen saturation <90% at rest (on ambient air).
  • Clinically significant hepatic disease.
  • Active infection requiring systemic therapy (minor infections may be allowed at the discretion of the investigator).
  • Subjects unwilling to accept blood products as medically indicated.
  • Vaccination with live vaccines within 4 weeks of the first dose of treatment and while on study is prohibited. Inactivated vaccines may be administered.
  • History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to bintrafusp alfa. Participants with history of severe hypersensitivity reaction to monoclonal antibodies (grade >= 3 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5) will be evaluated by the allergy/immunology team prior to enrollment.
  • History of second malignancy within 3 years of enrollment except for the following: adequately treated localized basal cell or squamous skin cancer, cervical carcinoma in situ, superficial bladder cancer, other localized malignancy which has been adequately treated or malignancy which does not require active systemic treatment (e.g., low risk chronic lymphocytic leukemia (CLL).
  • Pregnant or breastfeeding women are excluded from this study because the study medications have not been tested in pregnant women and there is potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study medications, breastfeeding should be discontinued if the mother is treated on this protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Background:

Olfactory neuroblastoma (ONB) is a rare cancer of the nasal cavity. At diagnosis, it is usually locally advanced. It tends to spread to the neck. Sometimes it spreads to the lungs and bones. Researchers want to find a better way to treat it.

Read more

Objective:

To learn if giving immunotherapy drug bintrafusp alfa can help ONB shrink or disappear.

Eligibility:

People aged 18 years and older diagnosed with recurrent or metastatic ONB that has not responded to standard treatment.

Design:

Participants will be screened with a medical history, blood and urine tests, and physical exam. Their ability to perform their normal activities will be assessed. They will have an electrocardiogram to evaluate their heart. They will have imaging scans and/or a nuclear bone scan, as needed. For some scans, they may receive a contrast dye.

Some screening tests will be repeated during the study.

Participants will receive bintrafusp alfa once every 2 weeks for 26 doses. They will get it intravenously over 60 minutes. They may get other medicines to prevent side effects. They will complete health questionnaires. Visits will last 4-6 hours.

Participants may have optional tumor biopsies.

Participants will have an end of treatment visit within 7 days after they stop taking the study drug. About 28 days after treatment ends, they will have a safety visit. They will have follow-up visits every 3 months for the first year, then every 6 months for years 2-5, and then once a year after that for the rest of their life. If their disease progresses, they may be eligible for re-treatment with the study drug

Read the detailed description

Background:

Olfactory neuroblastoma (ONB, also known as esthesioneuroblastoma), is a rare malignant neoplasm of the nasal cavity. At diagnosis, ONB is often locally advanced. It tends to invade locally and has high rates of regional spread to the neck, and distally to the lungs and bones. The 10-year survival rate for ONB is reported at 46%.

Standard of care treatment is surgical resection followed by adjuvant radiation. In advanced unresectable or metastatic cases, systemic chemotherapy is used off label, with agent selection based on published case series. Genomic profiling of ONB has not yet informed the utilization of an appropriate molecularly targeted treatment.

High programmed death-ligand 1 (PD-L1) expression by immunohistochemistry was shown in ONB tumor samples, providing a rationale for immune checkpoint blockade in ONB. In addition, high expression of transforming growth factor beta (TGF-beta) ligands has been identified in ONB, implying that additional benefit may be achieved by combination of checkpoint blockade with TGF-beta inhibition.

Bintrafusp alfa is a novel bifunctional fusion protein composed of a blocking monoclonal antibody against PD-L1 fused with the soluble extracellular domain of the human TGF-beta receptor II (TGF-betaRII), acting as a decoy target for TGF-beta. The safety profile of bintrafusp alfa in clinical trials to date has been shown to be manageable.

Objective:

To assess the objective response rate (ORR) to bintrafusp alfa in participants with recurrent/metastatic ONB, immune checkpoint-naive (CN)

Eligibility:

Participants must have histologically confirmed recurrent or metastatic ONB, not amenable to potentially curative local therapies.

Participants should have received at least one line of systemic therapy including a platinum agent, with evidence of disease progression clinically or radiographically.

Presence of >= 1 lesion measurable by Response Evaluation Criteria in Solid Tumors, (RECIST) 1.1 criteria

Age >= 18 years, men and women

Adequate organ function, and without serious comorbidity (e.g., autoimmune disease), that would preclude concurrent systemic treatment.

Design:

Single-institution, single-arm Phase II trial to determine overall response rate (ORR) in participants with recurrent/metastatic ONB treated with bintrafusp alfa.

Participants will be treated with bintrafusp alfa 1200 mg every 2 weeks for 26 doses.

The trial will initially enroll 12 checkpoint-naive (CN) participants; if responses are observed in one or more participants, the second stage will enroll another 9 CN participants to define the response rate to bintrafusp alfa, for a total of 21 CN participants.

An additional cohort of checkpoint-resistant (CR) participants will be enrolled and evaluated separately. Initially 5 CR participants will be enrolled; if responses are observed in one or more participants, the second stage will enroll another 3 participants, for a total of up to 8 CR participants. Accrual for CR participants will end when the preset number of CN participants has been accrued.

Being tested
Bintrafusp alfa/M7824, Ibuprofen, PET scan, CT scan, Tumor tissue biopsy
Keywords
ONB, M7824, nasal tumor
Medical subject headings
Esthesioneuroblastoma, Olfactory, Nose Neoplasms

What participants receive

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

  • Bintrafusp alfa/M7824Drug

    Also called M7824

    Participants will be treated with bintrafusp alfa 1200 mg every 2 weeks for 26 doses.

  • IbuprofenDrug

    Also called Advil, Advil Migraine

    400 mg or comparable non-steroidal anti-inflammatory drugs (NSAIDs) dose up to 2 hours before and 8 hours after the start of each dose for prophylaxis of flu-like symptoms.

  • PET scanDiagnostic test

    Also called Positron emission tomography scan

    Screening

  • CT scanDiagnostic test

    Also called Computed tomography scan

    Screening

  • Tumor tissue biopsyProcedure or surgery

    Also called Tumor tissue bx

    Baseline, and subsequent weeks as stipulated in the study calendar.

  • Brain MRIDiagnostic test

    Also called Brain magnetic resonance imaging

    Baseline

  • Dotate scanDiagnostic test

    Also called Ga-68 dotatate positron emission tomography/computed tomography scan

    Baseline

  • PET FDG scanDiagnostic test

    Also called fludeoxyglucose-18 (FDG) positron emission tomography (PET) scan

    Baseline

  • Nuclear bone scanDiagnostic test

    Baseline

  • EKGDiagnostic test

    Also called Electrocardiogram

    Baseline

Study groups in NCT05012098
Study groupRoleWhat they receive
1/Arm 1: Treatment with Bintrafusp AlfaExperimentalTreatment with Bintrafusp alfa
Receives: Drug: Bintrafusp alfa/M7824; Drug: Ibuprofen; Diagnostic Test: PET scan; Diagnostic Test: CT scan; Procedure: Tumor tissue biopsy; Diagnostic Test: Brain MRI; Diagnostic Test: Dotate scan; Diagnostic Test: PET FDG scan; Diagnostic Test: Nuclear bone scan; Diagnostic Test: EKG

What is being measured

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

  1. Percentage of Participants With an Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    ORR is defined as the percentage of evaluable participants who experience a response evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 reported along with a 95% two-sided confidence interval. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: Cycle 1 (28 days)

Secondary outcomes (4)

  1. Number of Participants Who Experience a Toxicity Related to Bintrafusp Alfa (M7824), by Grades (1, 2, 3, 4 and/or 5) and Type of Toxicity

    The number of participants who experience toxicity, by grade and type of toxicity related to Bintrafusp alfa (M7824) was assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Measured: up to 2 years

  2. Overall Survival (OS)

    OS is defined as the time from the date of first treatment to the date of death (any cause) using the Kaplan-Meier method.

    Measured: Through study completion, an average of 2 years

  3. Duration of Response (DOR)

    DOR is defined as the time measurement for complete response (CR) or partial response (PR) (whichever is first recorded) until the first documented date of progressive disease (PD) or death. ORR was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using the Kaplan-Meier method and reported along with a 95% two-sided confidence interval. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions.

    Measured: Through treatment completion, an average of 1 year

  4. Progression Free Survival (PFS)

    PFS is defined as the time from the date of first treatment to the date of disease progression or death (any cause) whichever occurs first, using the Kaplan-Meier method and reported along with a 95% confidence interval. Disease progression was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of the diameters of target lesions.

    Measured: Through treatment completion, an average of 1 year

Timeline

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

  1. First posted19 Aug 2021
  2. Study start21 Jun 2022
  3. Primary completion9 Jul 2024
  4. Study completion9 Jul 2024

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
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05012098
Sponsor's protocol ID
10000030
Other IDs
000030-C
Status last verified
Jul 2025
First submitted
18 Aug 2021
Last updated
8 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Publications

  • London NR Jr, Bracken-Clarke D, Xue E, Brownell I, Mydlarz WK, Turkbey EB, Cordes LM, Marte JL, Rooper LM, Shah SB, Manu M, Sargi ZB, Gulley JL, Floudas CS. Bintrafusp alfa for patients with recurrent or metastatic olfactory neuroblastoma. Cancer Immunol Immunother. 2026 Jun 17. doi: 10.1007/s00262-026-04462-4. Online ahead of print.

    PubMed 42307670

  • Haque F, Carrasquillo JA, Turkbey EB, Mena E, Lindenberg L, Eclarinal PC, Nilubol N, Choyke PL, Floudas CS, Lin FI, Turkbey B, Harmon SA. An automated pheochromocytoma and paraganglioma lesion segmentation AI-model at whole-body 68Ga- DOTATATE PET/CT. EJNMMI Res. 2024 Nov 5;14(1):103. doi: 10.1186/s13550-024-01168-5.

    PubMed 39500789

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bintrafusp alfa/M7824, Ibuprofen and PET scan in people with Olfactory Neuroblastoma and Esthesioneuroblastoma, run by National Cancer Institute (NCI) at 1 site 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 0 inclusion and 29 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: finished, as of the sponsor's last update on 8 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With an Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (time frame: Cycle 1 (28 days)). 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 NCT05012098, which also lists 2 linked publications.

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 8 Aug 2025.

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