Preliminary Report of Academic CAR-T (ISIKOK-19) Cell Clinical Trial in Turkey: Characterization of Product and Outcomes of Clinical Application

Erdogan, E.; Yalcin, K.; Hemsinlioglu, C.; Sezgin, A.; Seyis, U.; Dilek Kancagi, D.; Tastan, C.; Yurtsever, B.; Turan, R. D.; Cakirsoy, D.; Abanuz, S.; Sir Karakus, G.; Elek, M.; Bekoz, H. S.; Gemici, A. I.; Sargin, D.; Arat, M.; Ferhanoglu, B.; Pekguc, E.; Ornek, S.; Buyuktas, D.; Birgen, N.; Ratip, S.; Ovali, E.

Objective: Chimeric antigen receptor T (CAR-T) cell therapies already made an impact on the treatment of B cell malignancies. Although CAR-T cell therapies are promising, there are concerns with commercial products regarding their affordability and sustainability. In this preliminary study, results of the first productional and clinical data of academic CAR-T cell (ISIKOK-19) from Turkey are presented. Materials and Methods: A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy in patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. Production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusion is presented in this study. Results: Nine patients were enrolled for the trial (ALL n=5 and NHL n=4) but only 7 patients could receive the treatment. Two out of three ALL patients and three out of four NHL patients had complete/partial response (ORR 72%). Four patients (57%) had CAR-T-related toxicities (CRS, CRES, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up. Conclusion: Production efficacy and fulfilling the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles are acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19 positive tumors. The findings of this study need to be supported by the currently ongoing clinical trial of ISIKOK-19.