Abstract A038: Enrollment of pediatric and adolescent patients with MAGE-A4+ advanced synovial sarcoma into cohort 2 of SPEARHEAD-1: a phase 2 trial of afamitresgene autoleucel (“afami-cel” [formerly ADP-A2M4])
Authors: Lunt Colin , D’Angelo Sandra P. , Razak Albiruni Ryan Abdul , Wagner Michael J. , Van Tine Brian A. , Ganjoo Kristen , Blay Jean-Yves , Araujo Dejka M. , Agulnik Mark , Glod John W. , Van Winkle Erin , Elefant Erica , Biswas Swethajit , Williams Dennis , Le Cesne Axel 
Published: September 2022

Abstract
Background: Afami-cel is an autologous, specific peptide enhanced affinity receptor T-cell therapy genetically engineered to target MAGE-A4+ solid tumors in HLA-A*02+ patients. SPEARHEAD-1 (NCT04044768) is a Phase 2, two-cohort, single-arm, open-label trial evaluating afami-cel in patients with advanced/metastatic synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) and is the largest trial in metastatic synovial sarcoma to date. Preliminary data from Cohort 1 in 47 heavily pre-treated patients aged 16–75 years from 22 centers in North America and Europe, showed an overall response rate (ORR) per independent review of 34.0% (14/39 [35.9%] in synovial sarcoma; 2/8 [25%] in MRCLS) and a favorable benefit–risk profile with mainly low-grade cytokine release syndrome and tolerable/reversible hematologic toxicities.1 The reported ORR in synovial sarcoma in Cohort 1 was higher than reported ORRs for current standard-of-care therapies, such as pazopanib and trabectedin, in the second-line metastatic setting.2 As synovial sarcoma is the most common malignant nonrhabdomyosarcoma soft-tissue sarcoma in children and adolescents with few treatment options, especially for recurrent disease, the trial opened a second cohort to allow enrollment of pediatric patients with MAGE-A4+ synovial sarcoma who experienced disease progression post first-line chemotherapy, and to better understand MAGE-A4 tumor expression in children. Methods: Cohort 2 of the SPEARHEAD-1 trial is enrolling patients with advanced synovial sarcoma who are at least 10 years old and weigh at least 40 kg. The planned enrollment is 45 patients, including up to 13 children, to enable a pooled analysis of ORR in &gt;90 patients across Cohorts 1 and 2. HLA and MAGE-A4+ screening in Cohort 2 is conducted at a central laboratory using the same method as Cohort 1; MAGE-A4 testing is done using a clinical trial assay. All patients enrolled in Cohort 2 undergo apheresis and their isolated T-cells are then transduced with the MAGE-A4c1032 TCR using a lentivirus vector, followed by ex vivo expansion. Prior to afami-cel infusion of 1–10 × 109 transduced T-cells, patients will receive lymphodepleting chemotherapy consisting of fludarabine (30 mg/m2/day for 4 days) and cyclophosphamide (600 mg/m2/day for 3 days). Disease will be assessed by independent review per RECIST v1.1 using computerized tomography or magnetic resonance imaging at weeks 4, 8, 12, 16, 24, and every 2 months thereafter until confirmed disease progression. Patients enter long-term follow-up for 15 years. 1. Van Tine BA, et al. Paper 30: CTOS 2021; Virtual 2. Carroll C, et al. Cancer Res 2021;81(13_Suppl): Abstract nr 2630.
Citation Format: Colin Lunt, Sandra P. D’Angelo, Albiruni Ryan Abdul Razak, Michael J. Wagner, Brian A. Van Tine, Kristen Ganjoo, Jean-Yves Blay, Dejka M. Araujo, Mark Agulnik, John W. Glod, Erin Van Winkle, Erica Elefant, Swethajit Biswas, Dennis Williams, Axel Le Cesne. Enrollment of pediatric and adolescent patients with MAGE-A4+ advanced synovial sarcoma into cohort 2 of SPEARHEAD-1: a phase 2 trial of afamitresgene autoleucel (“afami-cel” [formerly ADP-A2M4]) [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr A038.