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

Esthesioneuroblastoma Clinical Trial

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

Status Active, not recruiting

Clinical 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.

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

Clinical Trial 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 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 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 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. ;

Related Conditions & MeSH terms

• Esthesioneuroblastoma
• Esthesioneuroblastoma, Olfactory
• Neuroblastoma
• Olfactory Neuroblastoma

• NCT number: NCT05012098
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 21, 2022
• Completion date: August 31, 2025