scholarly journals Local delivery of CAR T cells targeting fibroblast activation protein is safe in patients with pleural mesothelioma: first report of FAPME, a phase I clinical trial

2021 ◽  
Vol 32 (1) ◽  
pp. 120-121
Author(s):  
S. Hiltbrunner ◽  
C. Britschgi ◽  
P. Schuberth ◽  
L. Bankel ◽  
T.D.L. Nguyen-Kim ◽  
...  
2015 ◽  
Vol 23 ◽  
pp. S188-S189 ◽  
Author(s):  
Jae H. Park ◽  
Isabelle Riviere ◽  
Xiuyan Wang ◽  
Yvette Bernal ◽  
Elizabeth Halton ◽  
...  

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 3008-3008 ◽  
Author(s):  
Nabil M. Ahmed ◽  
Vita S Brawley ◽  
Oumar Diouf ◽  
Alexia Ghazi ◽  
Joanna Yi ◽  
...  

2019 ◽  
Vol 37 ◽  
pp. 166-167 ◽  
Author(s):  
C.L. Batlevi ◽  
M.L. Palomba ◽  
J. Park ◽  
E. Mead ◽  
B. Santomasso ◽  
...  

2015 ◽  
Vol 23 ◽  
pp. S9 ◽  
Author(s):  
Nabil Ahmed ◽  
Vita Brawley ◽  
Oumar Diouf ◽  
Amanda Wakefield ◽  
Aidin Ashoori ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10035-10035
Author(s):  
Payal D Shah ◽  
Alexander Chan Chi Huang ◽  
Xiaowei Xu ◽  
Paul J. Zhang ◽  
Robert Orlowski ◽  
...  

10035 Background: Advanced relapsed/refractory melanoma and metastatic triple-negative breast cancer are lethal diseases for which effective therapies are limited. We conducted a pilot phase I clinical trial (NCT03060356) to establish the safety and feasibility of intravenous autologous chimeric antigen receptor (CAR) T cell immunotherapy targeting cMET, a cell-surface antigen that is highly expressed in these cancers. Methods: Subjects had metastatic or unresectable melanoma (Mel) or triple-negative breast cancer (BC) with ≥30% expression of cMET on archival tissue or screening biopsy. Eligible subjects had measurable disease and progression on at least 1 prior therapy. Patients (pts) received up to 6 doses (1x108 total T-cells per dose) of RNA electroporated anti-cMET CAR T cells over a 2-week period without antecedent lymphodepleting chemotherapy. Subjects underwent pre- and post-infusion biopsies. The primary objective was to determine feasibility and safety of treatment. Results: 77 subjects (39 mel, 38 BC) were prescreened for tumor cMET expression and 37 (17 mel, 20 BC) met the eligibility threshold. Seven pts (4 BC, 3 Mel) received cMET-directed CAR T infusions on study. Mean age was 50 years (35-64); median (M) ECOG 0 (0-1); M prior lines of chemotherapy/immunotherapy were 4/0 for BC pts and 1/3 for Mel pts. 6 of 7 pts received all planned CAR T cell infusions, and 1 received 5 infusions. 5 pts experienced grade (G) 1 or G 2 toxicity that was possibly or definitely related to study. Toxicities occurring in ≥1 pt included: anemia (n = 3), fatigue (n = 2), and malaise (n = 2). No G ≥3 toxicities or cytokine release syndrome were observed. No pts discontinued therapy due to toxicity. Best response was stable disease in 4 pts (2 BC, 2 Mel) and PD in 3 pts (2 BC, 1 Mel). Messenger RNA signals corresponding to CAR T cells were detected by RT-PCR in the peripheral blood of all pts during the infusion period and in 2 pts after the infusion period. 6 pts underwent baseline biopsy and 4 pts underwent post-infusion biopsy. Immunohistochemical stains of CD3, CD4, CD8, CD163, L26, PD1, PDL1, Foxp3, Ki67, Granzyme B and Phospho-S6 were performed on pre- and post-treatment tissue biopsies and are being evaluated. Conclusions: Intravenous administration of RNA-electroporated cMET-directed CAR T cells was safe and feasible. Future directions include examination of this target using a lentiviral construct in combination with lymphodepleting chemotherapy. Clinical trial information: NCT03060356.


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