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

A Phase 2 Trial of IMC-F106C, a PRAME Targeted ImmTAC, in Rare Cancers

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Synovial Sarcoma; Metastatic Myxoid Liposarcoma; Unresectable Synovial Sarcoma; Unresectable Myxoid Liposarcoma
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Procedure: Biopsy Procedure; Biological: Anti-PRAME T-cell Receptor/Anti-CD3 scFv Fusion Protein IMC-F106C

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the efficacy, as defined by overall response rate (ORR), of anti-PRAME T-cell receptor/anti-CD3 scFv fusion protein IMC-F106C (brenetafusp [IMC-F106C]) in patients with preferentially expressed antigen of melanoma (PRAME) positive synovial sarcoma and myxoid/round cell liposarcoma.

SECONDARY OBJECTIVES:

I. To estimate progression free survival (PFS) at 3 months, 12 months, and median PFS in patients with PRAME positive synovial sarcoma and myxoid/round cell liposarcoma.

II. To assess PRAME expression by ribonucleic acid sequencing (RNAseq) at baseline and correlate PRAME expression with response to brenetafusp (IMC-F106C).

III. To correlate PFS and disease control rate (DCR) with changes in circulating tumor deoxyribonucleic acid (DNA) (ctDNA).

IV. To determine the efficacy, as defined by ORR, of brenetafusp in the intention to treat population.

V. To estimate the PFS at 3 months, 12 months, and the median PFS in the intention to treat population.

EXPLORATORY OBJECTIVES:

I. To identify biomarkers associated with response to brenetafusp (IMC-F106C) in patients with PRAME positive synovial sarcoma and myxoid/round cell liposarcoma.

II. To detect the pathogenic fusion protein in circulating blood and to correlate changes in circulating tumor DNA with response.

III. To correlate DCR with tumor reduction.

OUTLINE:

Patients receive brenetafusp (IMC-F106C) intravenously (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 computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study as well as biopsy and blood sample collection on study.

After completion of study treatment, patients are followed for up to 30 days.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

• Patients with treated brain metastases are eligible if:

  • Follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  • Treated CNS lesions are asymptomatic and radiographically stable for ≥ 2 weeks after intervention (surgery and/or radiation)
  • Participants are neurologically stable off systemic corticosteroids for at least 2 weeks prior to enrollment
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
• The effects of brenetafusp (IMC-F106C) on the developing human fetus are unknown. For this reason and because ImmTAC agents are known to be teratogenic, women of child-bearing potential and their partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during study treatment, and for 5 months after the last dose of brenetafusp (IMC-F106C). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should not breastfeed while taking brenetafusp (IMC-F106C) and for 5 months after completion of treatment. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 5 months after completion of brenetafusp (IMC-F106C) administration
• Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (brenetafusp [IMC-F106C]); 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.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Procedure: Biopsy Procedure; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy; Biological: Anti-PRAME T-cell Receptor/Anti-CD3 scFv Fusion Protein IMC-F106C; Given IV; Other Names: ImmTAC IMC-F106C; ImmTAC Molecule IMC-F106C; Immune Mobilizing Monoclonal TCR Against Cancer IMC-F106C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Will be calculated using a Kaplan-Meier estimator. Will report the point estimates at specified timepoints (3 months, 6 months, 12 months) and the corresponding 95% confidence interval. Will also report the median PFS.	From study initiation to first evidence of disease progression or death, assessed at 3, 6, and 12 months
Overall survival (OS)	Will be calculated using a Kaplan-Meier estimator. Will report the point estimates at specified timepoints (3 months, 6 months, 12 months) and the corresponding 95% confidence interval. Will also report the median OS with the corresponding 95% confidence intervals (if evaluable).	At 3, 6, and 12 months
Preferentially expressed antigen of melanoma (PRAME) expression	PRAME expression in tumor will first be measured by transcriptomic (ribonucleic acid) assessment and immunohistochemistry and then will be correlated with response to treatment. Analysis will be primarily descriptive.	At baseline and end of treatment
Changes in circulating tumor deoxyribonucleic acid (ctDNA)	Changes in ctDNA will be correlated with the clinical outcomes of PFS and disease control rate (DCR).	At baseline, cycle 2 day 1, and end of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers associated with response	Multiplex imaging will be utilized. Biomarker analysis will be primarily descriptive and therefore not specifically powered. The main comparisons will be between the level of the biomarker among patients who had a tumor response to treatment (responders as determined with RECIST v1.1), and those who did not have a tumor response. For categorical biomarkers, the data will be summarized with contingency tables, and the association between the biomarker status and response status will be evaluated using a Fisher's exact test.	At baseline, cycle 1 day 14-21, and end of treatment
Pathogenic fusion protein	Will look for the sarcoma specific fusion protein in circulating blood and measure changes in ctDNA levels in response to treatment.	At baseline, cycle 2 day 1, and end of treatment
DCR and tumor volume	DCR will be correlated with reduction in tumor volume.	Up to 30 days post-treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michael Wagner, Dana-Farber - Harvard Cancer Center LAO

Study record dates

Study Major Dates

• Study Start (Estimated): September 11, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: July 3, 2026
• First Submitted That Met QC Criteria: July 3, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Neoplasms, Adipose Tissue; Liposarcoma; Sarcoma, Synovial; Liposarcoma, Myxoid; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: NCI-2026-04705 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); UM1CA186709 (U.S. NIH Grant/Contract); 10740 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No