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

  • Andreas Mackensen (Geteilte/r Erstautor/in)
  • John B A G Haanen (Geteilte/r Erstautor/in)
  • Christian Koenecke
  • Winfried Alsdorf
  • Eva Wagner-Drouet
  • Peter Borchmann
  • Daniel Heudobler
  • Barbara Ferstl
  • Sebastian Klobuch
  • Carsten Bokemeyer
  • Alexander Desuki
  • Florian Lüke
  • Nadine Kutsch
  • Fabian Müller
  • Eveline Smit
  • Peter Hillemanns
  • Panagiotis Karagiannis
  • Erol Wiegert
  • Ying He
  • Thang Ho
  • Qing Kang-Fortner
  • Anna Melissa Schlitter
  • Catrine Schulz-Eying
  • Andrew Finlayson
  • Carina Flemmig
  • Klaus Kühlcke
  • Liane Preußner
  • Benjamin Rengstl
  • Özlem Türeci (Geteilte/r Letztautor/in)
  • Uğur Şahin (Geteilte/r Letztautor/in)

Beteiligte Einrichtungen

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 .

Bibliografische Daten

OriginalspracheEnglisch
ISSN1078-8956
DOIs
StatusVeröffentlicht - 11.2023

Anmerkungen des Dekanats

© 2023. The Author(s).

PubMed 37872225