Testing the Anti-Cancer Drug, Brenetafusp (IMCF106C), in Rare Cancers

NCT07686367 | Not Yet Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2026-0470510740UM1CA186709
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies how well brenetafusp (IMC-F106C) works in treating patients with preferentially expressed antigen of melanoma (PRAME) positive synovial sarcoma and myxoid/round cell liposarcoma that has spread from where it first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Brenetafusp (IMC-F106C) is in a new class of immunotherapy called immune mobilizing monoclonal T-cell receptors against cancer (ImmTAC). Brenetafusp (IMC-F106C), may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

Conditions

Metastatic Myxoid Liposarcoma; Metastatic Synovial Sarcoma; Unresectable Myxoid Liposarcoma; Unresectable Synovial Sarcoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria. The time interval for best response evaluation is within the first 6 cycles (after the third response assessment on study), with confirmation of response allowed within 8 cycles (2 cycles after initial response). Each disease cohort will be considered separately. Will use a two-stage Minimax design.

  Up to 8 cycles (Cycle length = 21 days)

Secondary Outcomes (4)

• Progression free survival (PFS)

  From study initiation to first evidence of disease progression or death, assessed at 3, 6, and 12 months

• Overall survival (OS)

  At 3, 6, and 12 months

• Preferentially expressed antigen of melanoma (PRAME) expression

  At baseline and end of treatment

• Changes in circulating tumor deoxyribonucleic acid (ctDNA)

  At baseline, cycle 2 day 1, and end of treatment

Other Outcomes (3)

• Biomarkers associated with response

  At baseline, cycle 1 day 14-21, and end of treatment

• Pathogenic fusion protein

  At baseline, cycle 2 day 1, and end of treatment

• DCR and tumor volume

  Up to 30 days post-treatment

Study Arms (1)

Treatment (brenetafusp [IMC-F106C])

EXPERIMENTAL

Patients receive brenetafusp (IMC-F106C) IV over 15-60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the study as well as biopsy and blood sample collection on study.

Biological: Anti-PRAME T-cell Receptor/Anti-CD3 scFv Fusion Protein IMC-F106C; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Anti-PRAME T-cell Receptor/Anti-CD3 scFv Fusion Protein IMC-F106C BIOLOGICAL

Given IV

Also known as: ImmTAC IMC-F106C, ImmTAC Molecule IMC-F106C, Immune Mobilizing Monoclonal TCR Against Cancer IMC-F106C

Treatment (brenetafusp [IMC-F106C])

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (brenetafusp [IMC-F106C])

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (brenetafusp [IMC-F106C])

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (brenetafusp [IMC-F106C])

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (brenetafusp [IMC-F106C])

Eligibility Criteria

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

You may qualify if:

• Patients must have metastatic or unresectable synovial sarcoma or myxoid/round cell liposarcoma confirmed by molecular testing (fluorescence in situ hybridization \[FISH\], immunohistochemistry \[IHC\] for fusion protein, or next-generation sequencing \[NGS\])
• Patients must be HLA-A\*02:01 positive. If HLA-A\*02:01 status is already known (from standard of care testing in a Clinical Laboratory Improvement Act \[CLIA\]-certified laboratory, e.g., in synovial sarcoma), then results from the patient record should be submitted. For patients with unknown HLA-A\*02:01 status, pre-enrollment blood should be submitted for testing through the American National Red Cross Histocompatibility Laboratory Services - Philadelphia for testing
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam
• Patients must have received at least one line of systemic therapy (neo/adjuvant chemotherapy counts as a line of therapy). The number of prior lines for metastatic or unresectable disease is limited to three (3)
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of brenetafusp (IMC-F106C) in patients \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥ 70%)
• Absolute neutrophil count ≥ 1,000/mcL (within 28 days of study enrollment)
• Platelets ≥ 75,000/mcL (within 28 days of study enrollment)
• Hemoglobin (Hgb) ≥ 9 g/dL (within 28 days of study enrollment)
• Total bilirubin ≤ 2 × institutional upper limit of normal (ULN) (within 28 days of study enrollment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN (within 28 days of study enrollment)
• Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 (within 28 days of study enrollment)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

You may not qualify if:

• Patients who received prior treatment with an agent targeting PRAME
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to brenetafusp (IMC-F106C)
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
• Pregnant women are excluded from this study because brenetafusp (IMC-F106C) is an ImmTAC agent with the 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 brenetafusp (IMC-F106C), breastfeeding should be discontinued if the mother is treated with brenetafusp (IMC-F106C)
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease will not be eligible for either the synovial sarcoma or myxoid liposarcoma cohorts
• Patients who have received prior T-cell receptor T-cell (TCR-T) therapy (including prior treatment with Afamitresgene autoleucel)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Liposarcoma, Myxoid; Sarcoma, Synovial

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Michael Wagner

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2026
• First Posted: July 7, 2026
• Study Start (Estimated): September 11, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: July 7, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share