(P 542) ENROLLMENT OF PEDIATRIC PARTICIPANTS WITH MAGE-A4-POSITIVE SOLID TUMORS IN A PHASE 1/2, OPEN-LABEL, BASKET TRIAL OF AFAMITRESGENE AUTOLEUCEL ("AFAMI-CEL")

Objective: Afami-cel is an affinity-enhanced T-cell receptor (TCR) T-cell therapy genetically engineered to target melanoma-associated antigen A4 (MAGE-A4)-positive solid tumors in human leukocyte antigen (HLA) A*02-eligible patients. In the Phase 2, SPEARHEAD-1 (NCT04044768) trial evaluating afami-cel in participants with advanced/metastatic synovial sarcoma (SS) or myxoid/round cell liposarcoma, encouraging anti-tumor data and an acceptable benefit-to-risk profile are being used to support a Biologics License Application submission. Children and adolescents with rare, MAGE-A4–expressing solid tumors have few treatment options and may also potentially benefit from afami-cel. A Phase 1/2 clinical trial (NCT05642455) is therefore being initiated to evaluate the safety and anti-tumor activity of afami-cel as well as describe the prevalence of MAGEA4 expression in pediatric patients with relapsed/refractory solid tumors.

Methods: Participants aged 2–21 years old with SS, malignant peripheral nerve sheath tumor, neuroblastoma, or osteosarcoma who express at least one HLA-A*02 inclusion allele and no exclusion allele(s) and whose tumor expresses MAGE-A4 will be eligible for enrollment. Prior to undergoing leukapheresis to collect autologous cells for processing and manufacturing into afami-cel, participants (or their legally authorized representative) will be required to sign a treatment informed consent form. Lymphodepleting chemotherapy consisting of fludarabine (30 mg/m^2/day for 4 days) and cyclophosphamide (600 mg/m^2/day for 3 days) will be administered beginning one week prior to afami-cel infusion. Anti-cancer therapy may be administered between screening and leukapheresis and between leukapheresis and the start of lymphodepletion, but must adhere to mandatory washout periods. Participants will be assigned to one of two groups based on weight and may begin afami-cel dosing in parallel: Group 1 (≥40 kg) will receive a flat dose of 1–10×10^9 transduced T-cells, and Group 2 (≥10 kg to < 40 kg) will receive a weight-based dose of 0.025–0.200x10^9 transduced T-cells per kg. Up to 20 participants will be enrolled. Incidence of dose-limiting toxicities; adverse events (AEs); serious AEs; and the incidence, severity, and duration of AEs of special interest will be assessed along with objective response rate per RECIST v1.1 or the revised International Response Criteria for Neuroblastoma (2017).

Results: N/A. Submitting under Trials in Progress.

Conclusion: N/A. Submitting under Trials in Progress.