Circulating tumor DNA and association with CAR-T cell therapy response in gastric and pancreatic cancer patients.

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4053 Background: Circulating tumor DNA (ctDNA) is a form of cell free DNA that can be used to detect and measure cancer molecular residual disease (MRD) before and after systemic therapy. There are no data pertaining to the assessment of MRD in patients with solid tumors treated with chimeric antigen receptor T-cell (CAR-T) therapy. Here, we evaluated a tumor-informed ctDNA assay in the setting of gastric and pancreatic malignancies treated with claudin18.2 (CT041)-targeted CAR-T cell therapy (NCT04404595). Methods: A single-center review between 7/1/2021 – 1/1/2023 identified 10 patients with pancreatic or gastric carcinoma who received CAR-T CT041 cell therapy. Eight patients were ctDNA positive prior to treatment and had blood samples serially drawn before and after CAR-T cell therapy. Banked plasma was analyzed for ctDNA using a tumor-informed Signatera, mPCR-NGS ctDNA assay (Natera, Inc.). The correlative prognostic value of ctDNA to predict response after CAR-T cell therapy was analyzed by RECIST 1.1 criteria. Results: Pre- and post-treatment serial ctDNA was available for 8 of 10 (3/5 gastric and 5/5 pancreatic cancer) patients and all 8 were ctDNA positive prior to CAR-T CT041 cell therapy. The median nadir of ctDNA was on day 14 after CT041 infusion.Of the 8 patients with detectable ctDNA, 5 (62.5%) became undetectable at some time after CT041 therapy, while 3 (37.5%)remained ctDNA positive throughout treatment. The disease control rate (DCR) was 80% for anytime negative ctDNA patients (4/5). Of patients with responsive disease after CT041 CAR-T, 2/3 (67%) achieved undetectable ctDNA and 1/3 (33%) had a ctDNA reduction by 95%. Both patients with stable disease developed undetectable ctDNA. In those patients with progressive disease, 1/3 (33%) had a negative anytime ctDNA. One patient with a complete response had undetectable ctDNA and target lesion response, then later developed progressive disease detectable by ctDNA 3 months prior to radiography. Overall survival was higher (9.1 months vs. 3.7 months) in those who achieved anytime undetectable ctDNA. Conclusions: Tumor-informed ctDNA correlates with response to CAR-T cell therapy in gastrointestinal malignancies. Ongoing clinical trials of CT041 CAR-T cell therapy will continue ctDNA analysis prospectively. Characteristics of initially ctDNA positive patients receiving CAR-T therapy. Clinical trial information: NCT04404595 . [Table: see text]