دورية
CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial
| العنوان: | CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial |
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| المؤلفون: | Mackensen, Andreas, Haanen, John B.A.G., Koenecke, Christian, Alsdorf, Winfried, Wagner-Drouet, Eva, Borchmann, Peter, Heudobler, Daniel, Ferstl, Barbara, Klobuch, Sebastian, Bokemeyer, Carsten, Desuki, Alexander, Lüke, Florian, Kutsch, Nadine, Müller, Fabian, Smit, Eveline, Hillemanns, Peter, Karagiannis, Panagiotis, Wiegert, Erol, He, Ying, Ho, Thang, Kang-Fortner, Qing, Schlitter, Anna Melissa, Schulz-Eying, Catrine, Finlayson, Andrew, Flemmig, Carina, Kühlcke, Klaus, Preußner, Liane, Rengstl, Benjamin, Türeci, Özlem, Şahin, Uğur |
| المصدر: | Nature Medicine; November 2023, Vol. 29 Issue: 11 p2844-2853, 10p |
| مستخلص: | 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. ClinicalTrials.gov Identifier: NCT04503278. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 10788956 1546170X |
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| DOI: | 10.1038/s41591-023-02612-0 |