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

NCT05012098 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 10000030000030-C
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Olfactory Neuroblastoma; Esthesioneuroblastoma; Neoplasm of the Nasal Cavity

Keywords

ONB; M7824; nasal tumor

Outcome Measures

Primary Outcomes (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.

  Cycle 1 (28 days)

Secondary Outcomes (4)

• 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

  up to 2 years

• Overall Survival (OS)

  Through study completion, an average of 2 years

• Duration of Response (DOR)

  Through treatment completion, an average of 1 year

• Progression Free Survival (PFS)

  Through treatment completion, an average of 1 year

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Adverse Events were monitored/assessed from first drug administration through 30 days after the last dose of study drug is administered, an average of 6 months.

Study Arms (1)

1/Arm 1: Treatment with Bintrafusp Alfa

EXPERIMENTAL

Treatment with Bintrafusp alfa

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

Interventions

Bintrafusp alfa/M7824 DRUG

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

Also known as: M7824

1/Arm 1: Treatment with Bintrafusp Alfa

Ibuprofen DRUG

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.

Also known as: Advil, Advil Migraine

1/Arm 1: Treatment with Bintrafusp Alfa

PET scan DIAGNOSTIC_TEST

Screening

Also known as: Positron emission tomography scan

1/Arm 1: Treatment with Bintrafusp Alfa

CT scan DIAGNOSTIC_TEST

Screening

Also known as: Computed tomography scan

1/Arm 1: Treatment with Bintrafusp Alfa

Tumor tissue biopsy PROCEDURE

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

Also known as: Tumor tissue bx

1/Arm 1: Treatment with Bintrafusp Alfa

Brain MRI DIAGNOSTIC_TEST

Baseline

Also known as: Brain magnetic resonance imaging

1/Arm 1: Treatment with Bintrafusp Alfa

Dotate scan DIAGNOSTIC_TEST

Baseline

Also known as: Ga-68 dotatate positron emission tomography/computed tomography scan

1/Arm 1: Treatment with Bintrafusp Alfa

PET FDG scan DIAGNOSTIC_TEST

Baseline

Also known as: fludeoxyglucose-18 (FDG) positron emission tomography (PET) scan

1/Arm 1: Treatment with Bintrafusp Alfa

Nuclear bone scan DIAGNOSTIC_TEST

Baseline

1/Arm 1: Treatment with Bintrafusp Alfa

EKG DIAGNOSTIC_TEST

Baseline

Also known as: Electrocardiogram

1/Arm 1: Treatment with Bintrafusp Alfa

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed recurrent or metastatic olfactory neuroblastoma (ONB) not amenable to potentially curative local therapies. Review of tissue samples by Pathology at the National Institutes of Health (NIH) is preferred.
• Participants must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. A previously treated lesion by radiotherapy can be chosen as the target lesion only if progression in the respective lesion has been demonstrated during or following radiotherapy.
• Participants should have received at least one line of systemic therapy including a platinum agent, with evidence of disease progression clinically or radiographically.
• Men or Women \>=18 years of age on day of signing informed consent. Because no dosing or adverse event data are currently available on the use of bintrafusp alfa in participants \<18 years of age, children are excluded from this study.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\<2.
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count (ANC) \>=1,500/mcL
• Hemoglobin \>=9 g/dL (transfusions allowed)
• Platelets \>=100,000/mcL
• Serum Creatinine \<= 1.5 x upper limit of normal (ULN) OR Measured creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula may be used to estimate CrCl/eGFR \>=30 mL/min/1.73m\^2 for participant with creatinine levels \> 1.5 x institutional ULN
• Serum total bilirubin \<=1.5 x upper limit of normal (ULN) OR Direct bilirubin \<=ULN for participants with total bilirubin levels \>1.5 x ULN
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) \<=2.5 x ULN
• The effects of immunotherapy on the developing human fetus are unknown. Therefore, participants must use effective methods of contraception (such as implants, injectables, combined oral contraceptives, intrauterine device (IUDs), sexual abstinence or vasectomized partner).
• Women of child-bearing potential (WOCBP: any woman who has experienced menarche and has not had hysterectomy or bilateral oophorectomy or is not postmenopausal (amenorrheic 12 months or more following cessation of exogenous hormonal treatments; if \<50 years old need follicle stimulating hormone (FSH) in the post-menopausal range)) must agree to use highly effective contraception prior to study entry and for up to 65 days following the last dose of study treatment.
• Men must agree to use highly effective contraception prior to study entry and up to 125 days following the last dose of study treatment.

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 39500789 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Esthesioneuroblastoma, Olfactory; Nose Neoplasms

Interventions

Ibuprofen; Positron-Emission Tomography; Tomography, X-Ray Computed; Radionuclide Imaging; Electrocardiography

Condition Hierarchy (Ancestors)

Neuroblastoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Olfactory Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Skull Neoplasms; Bone Neoplasms; Neoplasms by Site; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Bone Diseases; Musculoskeletal Diseases; Nose Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Image Enhancement; Photography; Tomography; Diagnostic Techniques, Radioisotope; Radiographic Image Enhancement; Radiography; Tomography, X-Ray; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis

Results Point of Contact

• Title: Dr. Charalampos Floudas
• Organization: National Cancer Institute

charalampos.floudas@nih.gov

240-858-3032

Study Officials

• Charalampos Floudas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 19, 2021
• Study Start: June 21, 2022
• Primary Completion: July 9, 2024
• Study Completion: July 9, 2024
• Last Updated: August 8, 2025
• Results First Posted: August 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)