636 BASECAMP-1: A master prescreening study to identify patients with high-risk or metastatic solid tumors with HLA loss of heterozygosity (LOH) in preparation for Tmod CAR T-cell therapy trials

• DOI: 10.1136/jitc-2023-sitc2023.0636
• Publication Date: 2023-10-31T14:07:01Z
• Authors: Diane M Simeone; J Randolph Hecht; Caleb Smith; Marwan Fakih; Theodore Welling; Edward Garon; M Pia Morelli; Patrick M Grierson; Kedar Kirtane; Peter Vu; Saurabh Dahiya; Frederick L Locke; Oliver Dorigo; Jong Chul Park; Caron Jacobson; Jennifer Specht; Tomislav Dragovich; Ariane Lozac’hmeur; Jessica Tebbets; Gayanie Ong; William Y Go; John Welch; Eric W Ng; David Maloney; Marcela Maus; Julian Molina
• Keywords: Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RC254-282

<h3>Background</h3> Chimeric antigen receptor (CAR) T-cell therapy has been challenging in solid tumors due to an absence of tumor-specific targets and the resultant on-target, off-tumor toxicity. Tmod, a novel logic-gated CAR therapy, utilizes blocking discriminate tumor from normal cells, thus mitigating toxicity (figure 1).^{1 2} The blocker recognizes human leukocyte (HLA), that is subject LOH.^{3 4} Among advanced colorectal, pancreatic, non-small cell lung cancers, HLA LOH occurs 15.6%, 19.6%, 23.1% patients, respectively (Tempus Database).⁵ However, can only be therapeutically exploited if patients are identifiable through feasible clinical workflow. BASECAMP-1 ongoing prescreening study to: 1) Identify with tumor-associated eligible for Tmod 2) Obtain leukapheresis preparation autologous trials EVEREST-1 (A2B530 targeting carcinoembryonic antigen; NCT05736731) EVEREST-2 (A2B694 mesothelin). <h3>Methods</h3> (NCT04981119) eligibility 2 parts 2). Patients metastatic or at high risk relapse will screened germline HLA-A*02. Tumor tissue HLA-A*02:01 heterozygosity analyzed somatic via Tempus next-generation sequencing testing. In addition, may identified AWARE program. analyzes submitted as part patient's routine workup. Institutional investigators then informed molecular results communicate treating physicians regarding enrollment opportunities. demonstrating HLA-A*02 subsequent leukapheresis, banked T cells available studies. <h3>Results</h3> As June 1, 2023, 664 were consented 9 institutions 3). status was determined 584 patients; 234 heterozygous (40%). 117 13 positive (11%). program deployed since January 2022. We have 52 across sites study-specific disease types LOH; these, currently being screened, 23 found ineligible, 16 consented. This demonstrated feasibility leveraging diagnostic during workup identify rare, molecularly defined personalized <h3>Trial Registration</h3> NCT04981119 Please note, this trial screening/non-interventional trial. <h3>References</h3> 1. Hamburger AE, DiAndreth B, Cui J, <i>et al</i>. Engineered directed allelic loss. <i>Mol Immunol.</i> 2020;<b>128</b>:298- 2. A, Xu H, Kamb A. cellular logic gate solution tumor-selective immunotherapy. Clin Immunol. 2022;<b>241</b>:109030. 3. Sandberg ML, Wang X, Martin AD, A antigen-specific selectively loss vitro vivo. <i>Sci Transl Med.</i> 2022;<b>14</b>:eabm0306. 4. Tokatlian T, Asuelime GE, Mock J-Y, Mesothelin-specific CAR-T incorporates HLA-gated safety mechanism kills cells. <i>J Immunother Cancer.</i> 2022;<b>10</b>:e003826. 5. Simeone DM, Hecht R, Patel SP, BASECAMP-1: Leveraging (HLA) (LOH) by (NGS) relapsed future therapy. Oncol</i>. 2022;<b>40</b>(16_Suppl):TPS2676. <h3>Ethics Approval</h3> approved site IRBs