CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial PMID: 37872225

ADC Targets in Oncology

2026-04-10

CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial

Nat Med. 2023 Nov;29(11):2844-2853. doi: 10.1038/s41591-023-02612-0.

Andreas Mackensen ^# ¹ ² , John B A G Haanen ^# ³ ⁴ , Christian Koenecke ⁵ , Winfried Alsdorf ⁶ , Eva Wagner-Drouet ⁷ , Peter Borchmann ⁸ , Daniel Heudobler ² ⁹ , Barbara Ferstl ¹ ² , Sebastian Klobuch ³ , Carsten Bokemeyer ⁶ , Alexander Desuki ⁷ , Florian Lüke ² ⁹ , Nadine Kutsch ⁸ , Fabian Müller ¹ ² , Eveline Smit ³ , Peter Hillemanns ¹⁰ , Panagiotis Karagiannis ⁶ , Erol Wiegert ¹¹ , Ying He ¹² , Thang Ho ¹³ , Qing Kang-Fortner ¹³ , Anna Melissa Schlitter ¹² , Catrine Schulz-Eying ¹² , Andrew Finlayson ¹² , Carina Flemmig ¹² , Klaus Kühlcke ¹⁴ , Liane Preußner ¹² , Benjamin Rengstl ¹² ¹⁵ , Özlem Türeci ¹² ¹³ ¹⁴ ¹⁵ , Uğur Şahin ¹⁶ ¹⁷ ¹⁸ ¹⁹

Affiliations

1. University Hospital Erlangen, Department of Internal Medicine 5, Hematology/Oncology, Erlangen, Germany.
2. Bavarian Cancer Research Center (BZKF), Erlangen, Germany.
3. Netherlands Cancer Institute, Division of Medical Oncology, Amsterdam, the Netherlands.
4. Leiden University Medical Center, Department of Oncology, Leiden, the Netherlands.
5. Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany.
6. University Medical Center Hamburg-Eppendorf, Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, Hamburg, Germany.
7. University Medical Center Mainz, 3rd Medical Department, Hematology and Oncology, Mainz, Germany.
8. University Hospital of Cologne, Department I of Internal Medicine and Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, Cologne, Germany.
9. University Hospital Regensburg, Department of Internal Medicine III, Hematology and Oncology, Regensburg, Germany.
10. Hannover Medical School, Department of Gynecology and Obstetrics, Hannover, Germany.
11. Bexon Clinical Consulting, Upper Montclair, NJ, USA.
12. BioNTech SE, Mainz, Germany.
13. BioNTech US, Cambridge, MA, USA.
14. BioNTech Innovative Manufacturing Services GmbH, Idar-Oberstein, Germany.
15. BioNTech Cell & Gene Therapies GmbH, Mainz, Germany.
16. BioNTech SE, Mainz, Germany. [email protected].
17. BioNTech US, Cambridge, MA, USA. [email protected].
18. BioNTech Innovative Manufacturing Services GmbH, Idar-Oberstein, Germany. [email protected].
19. BioNTech Cell & Gene Therapies GmbH, Mainz, Germany. [email protected].
# Contributed equally.

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. ClinicalTrials.gov Identifier: NCT04503278 .