Mackensen, Haanen et al. reported interim data from a phase 1/2 trial in 22 heavily pretreated patients with relapsed/refractory Claudin 6 (CLDN6)-positive solid tumors. Two dose levels of CLDN6 CAR T cells were compared with or without a CAR T cell-amplifying RNA/lipid vaccine (CARVac). Overall safety and adverse events of both doses were manageable, and CARVac addition was well tolerated. CAR T cell engraftment was robust, and patients with germ cell tumors at the higher dose exhibited the greatest response rate (ORR 57%; 4 of 7), while the unconfirmed ORR in 21 patients was 33%, including 1 CR. An amended trial using an automated manufacturing process is ongoing.
Contributed by Katherine Turner
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 .
Author Info: (1) University Hospital Erlangen, Department of Internal Medicine 5, Hematology/Oncology, Erlangen, Germany. Bavarian Cancer Research Center (BZKF), Erlangen, Germany. (2) Netherla
Author Info: (1) University Hospital Erlangen, Department of Internal Medicine 5, Hematology/Oncology, Erlangen, Germany. Bavarian Cancer Research Center (BZKF), Erlangen, Germany. (2) Netherlands Cancer Institute, Division of Medical Oncology, Amsterdam, the Netherlands. Leiden University Medical Center, Department of Oncology, Leiden, the Netherlands. (3) Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany. (4) University Medical Center Hamburg-Eppendorf, Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, Hamburg, Germany. (5) University Medical Center Mainz, 3rd Medical Department, Hematology and Oncology, Mainz, Germany. (6) University Hospital of Cologne, Department I of Internal Medicine and Center for Integrated Oncology Aachen Bonn Cologne Dsseldorf, Cologne, Germany. (7) Bavarian Cancer Research Center (BZKF), Erlangen, Germany. University Hospital Regensburg, Department of Internal Medicine III, Hematology and Oncology, Regensburg, Germany. (8) University Hospital Erlangen, Department of Internal Medicine 5, Hematology/Oncology, Erlangen, Germany. Bavarian Cancer Research Center (BZKF), Erlangen, Germany. (9) Netherlands Cancer Institute, Division of Medical Oncology, Amsterdam, the Netherlands. (10) University Medical Center Hamburg-Eppendorf, Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, Hamburg, Germany. (11) University Medical Center Mainz, 3rd Medical Department, Hematology and Oncology, Mainz, Germany. (12) Bavarian Cancer Research Center (BZKF), Erlangen, Germany. University Hospital Regensburg, Department of Internal Medicine III, Hematology and Oncology, Regensburg, Germany. (13) University Hospital of Cologne, Department I of Internal Medicine and Center for Integrated Oncology Aachen Bonn Cologne Dsseldorf, Cologne, Germany. (14) University Hospital Erlangen, Department of Internal Medicine 5, Hematology/Oncology, Erlangen, Germany. Bavarian Cancer Research Center (BZKF), Erlangen, Germany. (15) Netherlands Cancer Institute, Division of Medical Oncology, Amsterdam, the Netherlands. (16) Hannover Medical School, Department of Gynecology and Obstetrics, Hannover, Germany. (17) University Medical Center Hamburg-Eppendorf, Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, Hamburg, Germany. (18) Bexon Clinical Consulting, Upper Montclair, NJ, USA. (19) BioNTech SE, Mainz, Germany. (20) BioNTech US, Cambridge, MA, USA. (21) BioNTech US, Cambridge, MA, USA. (22) BioNTech SE, Mainz, Germany. (23) BioNTech SE, Mainz, Germany. (24) BioNTech SE, Mainz, Germany. (25) BioNTech SE, Mainz, Germany. (26) BioNTech Innovative Manufacturing Services GmbH, Idar-Oberstein, Germany. (27) BioNTech SE, Mainz, Germany. (28) BioNTech SE, Mainz, Germany. BioNTech Cell & Gene Therapies GmbH, Mainz, Germany. (29) BioNTech SE, Mainz, Germany. BioNTech US, Cambridge, MA, USA. BioNTech Innovative Manufacturing Services GmbH, Idar-Oberstein, Germany. BioNTech Cell & Gene Therapies GmbH, Mainz, Germany. (30) BioNTech SE, Mainz, Germany. Ugur.Sahin@biontech.de. BioNTech US, Cambridge, MA, USA. Ugur.Sahin@biontech.de. BioNTech Innovative Manufacturing Services GmbH, Idar-Oberstein, Germany. Ugur.Sahin@biontech.de. BioNTech Cell & Gene Therapies GmbH, Mainz, Germany. Ugur.Sahin@biontech.de.
