2022-LBA-414-ESGO Preliminary clinical outcome of ADP-A2M4CD8, a next-generation autologous T-cell receptor T-cell therapy, in patients with advanced epithelial ovarian cancer

• Published in: International journal of gynecological cancer Vol. 32; no. Suppl 2; pp. A472 - A473
• Main Authors: Moore, Kathleen, Asch, Adam, Moreno, Victor, Calvo, Emiliano, Butler, Marcus, Zugazagoitia, Jon, Hong, David, Galal, Ahmed, Ostios, Lorena, de Miguel, Maria, Lin, Quan, Annareddy, Thejo, Brophy, Francine, Rosenberg, Marisa, Seiders, Theresa, Naidoo, Revashnee, Bath, Natalie, Saro, Jose, Norry, Elliot, Clarke, Jeffrey
• Format: Journal Article
• Language: English
• Published: Oxford BMJ Publishing Group Ltd 27.10.2022; BMJ Publishing Group LTD
• Subjects: Antigens; Cancer therapies; Chemotherapy; Cytokines; Hypoxia; Late breaking abstracts; Neurotoxicity; Ovarian cancer; Response rates; Tumors
• ISSN: 1048-891X; 1525-1438
• DOI: 10.1136/ijgc-2022-ESGO.1019

IntroductionADP-A2M4CD8, a next-generation specific peptide enhanced affinity receptor (SPEAR) T-cell therapy supplemented with a CD8α co-receptor, is being evaluated in the Phase 1 SURPASS trial (NCT04044859) in multiple solid tumours, including ovarian cancer. Promising anti-tumour activity, including a 36% overall response rate (1 complete response [CR], 7 partial responses [PR] in 22 evaluable patients; 2 August 2021 data cut-off) and a favourable benefit to risk profile were reported.1 We report preliminary anti-tumour activity in ovarian cancer and updated safety in all tumours.MethodsSURPASS is a first-in-human trial evaluating ADP-A2M4CD8 using a modified 3+3 design, with 2 dose cohorts and an expansion cohort.1 T-cells are collected by leukapheresis, transduced, and infused into the patient after lymphodepletion. Eligible patients express human leukocyte antigen A*02 with melanoma-associated antigen (MAGE)-A4-positive tumours. Patients with ovarian cancer must have received platinum-based chemotherapy and progressed ≤12 months post platinum therapy.ResultsAs of 1 August 2022, 14 patients with ovarian cancer had received 1.14–9.95×109 transduced T-cells. Median age was 59 years (range, 40–75); median number of prior systemic therapy regimens was 4 (range, 2–8); median MAGE-A4 expression H-score was 237.5 (range, 95–300). Adverse events in the overall population were consistent with lymphodepletion chemotherapy or cellular therapy; similar safety results were seen in the ovarian cancer subgroup (table 1). There was 1 Grade 5 cytokine release syndrome. Best overall responses were 1 CR, 4 PR, 6 stable disease (SD), 2 progressive disease and 1 not evaluable, giving a 36% overall response rate and a 79% disease control rate (CR+PR+SD, figure 1).Abstract 2022-LBA-414-ESGO Table 1Adverse event (AE) summary Preferred term Serious AEs in ≥5% of patients overall, N=44 Serious AEs related to T-cell infusion in ≥5% of patients overall, N=44 Serious AEs in patients with ovarian cancer, N=14 Serious AEs related to T-cell infusion in patients with ovarian cancer, N=14 Any serious AE, n (%) 27 (61.4) 21 (47.7) 11 (78.6) 10 (71.4) Cytokine release syndrome (CRS) 14 (31.8) 14 (31.8) 7 (50.0) [including 1 grade 5 event in a 60-year-old with large tumor burden in lungs and previous lung radiotherapy. Cause of death: pneumonia and CRS] 7 (50.0) Hypoxia 3 (6.8) 3 (6.8) 3 (21.4) 3 (21.4) Immune effector cell-associated neurotoxicity syndrome 3 (6.8) 3 (6.8) 1 (7.1) 1 (7.1) Pyrexia 3 (6.8) 2 (4.5) 2 (14.3) 2 (14.3) Preferred term AEs related to T-cell infusion in ≥12% of patients overall, N=44 AEs related to T-cell infusion in patients with ovarian cancer, N=14 Any AE 40 (90.9) 14 (100.0) Cytokine release syndrome 32 (72.7) 11 (78.6) Neutropenia/neutrophil count decreased 13 (29.5) 4 (28.6) Anemia/RBC decreased 10 (22.7) 3 (21.4) Pyrexia 10 (22.7) 5 (35.7) Fatigue 9 (20.5) 4 (28.6) Leukopenia/WBC decreased 7 (15.9) 2 (14.3) Rash 7 (15.9) 3 (21.4) Thrombocytopenia/platelet count decreased 7 (15.9) 2 (14.3) Dyspnoea 6 (13.6) 3 (21.4) Hypoxia 6 (13.6) 3 (21.4) Immune effector cell-associated neurotoxicity syndrome 6 (13.6) 1 (7.1) Pleural effusion 6 (13.6) 1 (7.1) Abstract 2022-LBA-414-ESGO Figure 1ConclusionsADP-A2M4CD8 SPEAR T-cell therapy showed preliminary anti-tumour activity in heavily pre-treated patients with MAGE-A4+ advanced ovarian cancer, with tolerable emerging safety results. The trial now includes an anti-programmed death-ligand 1 combination treatment cohort. 1. Hong DS, et al. Ann Oncol. 2021;32(suppl5):540P.