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.
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)
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)
Single group
Anti-PRAME T-cell Receptor/Anti-CD3 scFv Fusion Protein IMC-F106C
Biological/VaccineGiven IV
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
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.
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.
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).
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.
Changes in circulating tumor deoxyribonucleic acid (ctDNA)
Changes in ctDNA will be correlated with the clinical outcomes of PFS and disease control rate (DCR).
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.
Pathogenic fusion protein
Will look for the sarcoma specific fusion protein in circulating blood and measure changes in ctDNA levels in response to treatment.
DCR and tumor volume
DCR will be correlated with reduction in tumor volume.
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