A pilot study of lymphodepletion intensity for PBMC-derived, neoantigen-specific CD8+ T cells (Neo-Ts) therapy in patients with advanced solid tumors.

person Dandan Li Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Dandan Li, Chao Chen, Jingjing Li, Jianhui Yue, Ya Ding, Hailun Wang, Zhaoduan Liang, Le Zhang, Si Qiu, Geng Liu, Yan Gao, Ying Huang, Dongli Li, Wei Liu, Xizhi Wen, Bo Li, Xiaoshi Zhang, Xi Zhang, Rui-Hua Xu

Authors person Dandan Li Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China info_outline Dandan Li, Chao Chen, Jingjing Li, Jianhui Yue, Ya Ding, Hailun Wang, Zhaoduan Liang, Le Zhang, Si Qiu, Geng Liu, Yan Gao, Ying Huang, Dongli Li, Wei Liu, Xizhi Wen, Bo Li, Xiaoshi Zhang, Xi Zhang, Rui-Hua Xu Organizations Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China, BGI-Shen zhen, Shen Zhen, China, BGI-Shen zhen, Shenzhen, China, BGI-Shenzhen, Shenzhen, China, Biotherapy Center, Sun Yat-sen University Cancer Center, 510060 Guangzhou, China., Guangzhou, China, Sun Yat-sen University Cancer Center, Guangzhou, China, BGI Genomics, BGI-Shenzhen, Shenzhen, China, State Key Laboratory of Oncology in South China,510060 Guangzhou, China., Guangzhou, China Abstract Disclosures Research Funding No funding received None. Background: Adoptive T cell therapy (ACT) using neoantigen-specific CD8+ T cells (Neo-Ts) derived from patient PBMC was recently developed aiming to target individual patient’s unique tumor mutations and increase treatment efficacy. But the optimal lymphodepletion intensity for Neo-T therapy has yet to be determined. Methods: In this phase I clinical trial (NCT02959905), we generated Neo-Ts from patients with locally advanced or metastatic melanoma or colon cancers that were refractory to standard therapies, and evaluated the effects of lymphodepletion at various dosages (high: 2x500 mg/m 2 cyclophosphamide and 2x25 mg/ m 2 fludarabine; low: 1x500 mg/m 2 cyclophosphamide and 2x25 mg/ m 2 fludarabine; and no lymphodepletion) during Neo-T therapy. The primary end point was safety and the secondary end point was objective response rate (ORR). Results: We showed that Neo-T therapy was safe with lymphodepletion at dosages from no lymphodepletion to high intensity. The median PFS was 7.1 months (95% CI:3.7-9.8), and median overall survival (OS) was 16.8 months (95% CI: 11.9-31.7). The ORR was 33.3% (3/9) among all groups. Three patients achieved PR, two of them were in the group without lymphodepletion. One of the PR patients refractory to prior anti-PD-1 therapy also responded to Neo-T therapy. Neoantigen specific TCRs were examined in two responding patients and showed expansion and persistence after treatment. Conclusions: Neo-T therapy with low intensity lymphodepletion or no lymphodepletion could be a safe and promising regimen for advanced solid tumors. Clinical trial information: NCT02959905.

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