TY - JOUR T1 - Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10<sup>+</sup> advanced non-small cell lung cancer JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2021-003581 VL - 10 IS - 1 SP - e003581 AU - George R Blumenschein AU - Siddhartha Devarakonda AU - Melissa Johnson AU - Victor Moreno AU - Justin Gainor AU - Martin J Edelman AU - John V Heymach AU - Ramaswamy Govindan AU - Carlos Bachier AU - Bernard Doger de Spéville AU - Matthew J Frigault AU - Anthony J Olszanski AU - Vincent K Lam AU - Natalie Hyland AU - Jean-Marc Navenot AU - Svetlana Fayngerts AU - Zohar Wolchinsky AU - Robyn Broad AU - Dzmitry Batrakou AU - Melissa M Pentony AU - Joseph P Sanderson AU - Andrew Gerry AU - Diane Marks AU - Jane Bai AU - Tom Holdich AU - Elliot Norry AU - Paula M Fracasso Y1 - 2022/01/01 UR - http://jitc.bmj.com/content/10/1/e003581.abstract N2 - Background ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T cells (ADP-A2M10) are genetically engineered autologous T cells that express a high-affinity melanoma-associated antigen A10 (MAGE-A10)-specific T-cell receptor (TCR) targeting MAGE-A10+ tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-003 was a phase I dose-escalation trial that aimed to evaluate the safety and antitumor activity of ADP-A2M10 in non-small cell lung cancer (NSCLC) (NCT02592577).Methods Eligible patients were HLA-A*02 positive with advanced NSCLC expressing MAGE-A10. Patients underwent apheresis; T cells were isolated, transduced with a lentiviral vector containing the TCR targeting MAGE-A10, and expanded. Patients underwent lymphodepletion with varying doses/schedules of fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 were administered at 0.08–0.12×109 (dose group 1), 0.5–1.2×109 (dose group 2), and 1.2–15×109 (dose group 3/expansion) transduced cells.Results Eleven patients (male, n=6; female, n=5) with NSCLC (adenocarcinoma, n=8; squamous cell carcinoma, n=3) were treated. Five, three, and three patients received cells in dose group 1, dose group 2, and dose group 3/expansion, respectively. The most frequently reported grade ≥3 adverse events were lymphopenia (n=11), leukopenia (n=10), neutropenia (n=8), anemia (n=6), thrombocytopenia (n=5), and hyponatremia (n=5). Three patients presented with cytokine release syndrome (grades 1, 2, and 4, respectively). One patient received the highest dose of lymphodepletion (fludarabine 30 mg/m2 on days –5 to –2 and cyclophosphamide 1800 mg/m2 on days −5 to −4) prior to a second infusion of ADP-A2M10 and had a partial response, subsequently complicated by aplastic anemia and death. Responses included: partial response (after second infusion; one patient), stable disease (four patients), clinical or radiographic progressive disease (five patients), and not evaluable (one patient). ADP-A2M10 were detectable in peripheral blood and in tumor tissue. Peak persistence was higher in patients who received higher doses of ADP-A2M10.Conclusions ADP-A2M10 demonstrated an acceptable safety profile and no evidence of toxicity related to off-target binding or alloreactivity. There was persistence of ADP-A2M10 in peripheral blood as well as ADP-A2M10 trafficking into the tumor. Given the discovery that MAGE-A10 and MAGE-A4 expression frequently overlap, this clinical program closed as trials with SPEAR T cells targeting MAGE-A4 are ongoing.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. The raw data sets generated, used, and analyzed during the current study are available from the corresponding author on reasonable request. ER -