Mackensen, Andreas and Haanen, John B. A. G. and Koenecke, Christian and Alsdorf, Winfried and Wagner-Drouet, Eva and Borchmann, Peter and Heudobler, Daniel and Ferstl, Barbara and Klobuch, Sebastian and Bokemeyer, Carsten and Desuki, Alexander and Lueke, Florian and Kutsch, Nadine and Mueller, Fabian and Smit, Eveline and Hillemanns, Peter and Karagiannis, Panagiotis and Wiegert, Erol and He, Ying and Ho, Thang and Kang-Fortner, Qing and Schlitter, Anna Melissa and Schulz-Eying, Catrine and Finlayson, Andrew and Flemmig, Carina and Kuehlcke, Klaus and Preussner, Liane and Rengstl, Benjamin and Tuereci, Oezlem and Sahin, Ugur (2023) CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial. NATURE PORTFOLIO, BERLIN.
Full text not available from this repository. (Request a copy)Abstract
The oncofetal antigen Claudin 6 (CLDN6) is highly and specifically expressed in many solid tumors, and could be a promising treatment target. We report dose escalation results from the ongoing phase 1/2 BNT211-01 trial evaluating the safety and feasibility of chimeric antigen receptor (CAR) T cells targeting the CLDN6 with or without a CAR-T cell-amplifying RNA vaccine (CARVac) at two dose levels (DLs) in relapsed/refractory CLDN6-positive solid tumors. The primary endpoints were safety and tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D). Secondary endpoints included objective response rate (ORR) and disease control rate. We observed manageable toxicity, with 10 out of 22 patients (46%) experiencing cytokine release syndrome including one grade 3 event and 1 out of 22 (5%) with grade 1 immune effector cell-associated neurotoxicity syndrome. Dose-limiting toxicities occurred in two patients at the higher DL, resolving without sequelae. CAR-T cell engraftment was robust, and the addition of CARVac was well tolerated. The unconfirmed ORR in 21 evaluable patients was 33% (7 of 21), including one complete response. The disease control rate was 67% (14 of 21), with stable disease in seven patients. Patients with germ cell tumors treated at the higher DL exhibited the highest response rate (ORR 57% (4 of 7)). The maximum tolerated dose and RP2D were not established as the trial has been amended to utilize an automated manufacturing process. A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials.
| Item Type: | Other |
|---|---|
| Uncontrolled Keywords: | CLAUDIN 6; ANTIGEN; CANCER; THERAPY; IMMUNOTHERAPY; LIPOSOMES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2024 13:50 |
| Last Modified: | 07 May 2024 13:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60734 |
Actions (login required)
 |
View Item |
