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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Given IV
Undergo biopsy
Undergo blood sample collection
Undergo CT
Undergo 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.
Time frame: Up to 8 cycles (Cycle length = 21 days)
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.
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: At baseline, cycle 2 day 1, and end of treatment
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