Abstract 5392
Background
Adoptive cellular therapy in patients (pts) with solid tumors is limited due to lack of cancer targets with high specificity or relapse often associated with loss of single antigen (Ag) expression. To address multiple novel tumor Ags, we utilized Ag-specific T cells (IMA101) against cancer targets. Target positive tumors were identified by qPCR. Expression levels predictive for Ag presentation were determined by mass spectrometry. Autologous T cells against ACTolog targets are in vitro primed in the presence of IL-21 followed by HLA tetramer-guided cell sorting and expansion prior to infusion.
Methods
HLA-A*02:01 positive pts with relapsed/refractory solid tumors are eligible for treatment if their tumors express ≥1 of 8 possible Ag targets from a predefined antigen warehouse. These pts undergo leukapheresis, followed by IMA101 cell manufacturing. Treatment consists of lymphodepletion (Fludarabine/Cyclophosphamide) followed by IMA101 infusion of up to 4 Ag-specific T cell products and IL-2.
Results
From 8/2017 to 5/2018, 86 pts were prescreened, 38 were HLA-A*02:01 positive, 18 had tumor biopsy, 11 had leukapheresis and 3 were treated so far: hormone receptor pos, HER2 neg. breast cancer (56 yr, fem.); synovial sarcoma (28 yr, fem.); and liposarcoma (36 yr, male); No. of prior therapies, 12, 6, 8, respectively. Respective time to recovery was: ANC >1.0: day 41, 8, and 61; Platelets > 50: day 47, no decrease <50, and 61. Pts developed Grade 1-2 cytokine release syndrome, without evidence of infection. The third patient developed bradycardia on day 9, which was reversible with discontinuation of IL-2. Peripheral blood analysis at 2 wks demonstrated that CD8+ T cells specific for cancer targets were 0.4%, 12%, and 46% of total circulating CD8+ T cells, respectively. Pts had disease stabilization at 6 wks.
Conclusions
In the 3 pts treated, treatment was tolerable. To our knowledge, this is the first time that pts received multiple defined Ag-specific products. Initial T-cell persistence data demostrated high prevalence and the expected T-cell phenotype, which are important prerequisites for clinical activity. The trial is ongoing.
Clinical trial identification
NCT02876510.
Legal entity responsible for the study
Immatics US, Inc.
Funding
Cancer Prevention Research Institute of Texas (DP150029).
Editorial Acknowledgement
Disclosure
H. Ma, C. Stewart, O. Schoor, D. Maurer, A. Satelli, G. Stephens, A. Mohamed, R. Mendrzyk: Employee: Immatics. P. Hwu, C. Yee: Stock option and scientific advisory board: Immatics. C. Reinhardt: Stock owner and employee: Immatics. H. Singh, S. Walter: Employee and stock option: Immatics. All other authors have declared no conflicts of interest.
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