BNT211 chimeric antigen receptor (CAR) T-cell therapy showed some signs of clinical activity and an increased persistence of cancer-specific CAR-T cells when combined with CARVac in patients with Claudin-6 (CLDN6)-positive refractory/relapsed solid tumors.1
Professor John Haanen, MD, PhD
Updated data from an ongoing first-in-human Phase 1/2 trial (NCT04503278) were presented by Professor John Haanen, MD, PhD, Netherlands Cancer Institute (NKI), Amsterdam, at the European Society for Medical Oncology (ESMO) Congress 2023, held October 20-24 in Madrid, Spain.1
“Our goal is to unlock the potential of CAR-T for solid tumors and to help improve the outcomes for a broad range of hard-to-treat tumors,” Prof. Özlem Türeci, MD, cofounder and chief medical officer, BioNTech, said in a statement.2 “BNT211 aims to address 2 of the key limitations of CAR-T cell approaches in solid tumors, namely the lack of suitable cancer-specific cell surface targets and the limited persistence of CAR-T cells. To address this challenge, we have designed a CLDN6-specific autologous CAR-T cell therapy that we combine with our mRNA-based vaccine CARVac.”
BNT211 is an autologous CAR-T cell therapy targeting CLDN6 and CARVacis a CLDN6-encoding, CAR-T cell amplifying RNA vaccine. The trial is enrolling participants with at least 50% tumor cells with 2+/3+ CLDN6 positivity and measurable disease per RECIST v1.1 or elevated tumor marker and ECOG performance status 0–1. The trial is primarily assessing safety, tolerability, and dose-limiting toxicities. Secondary outcomes include immunogenicity, overall response rate (ORR), disease control rate (DCR), duration of response, and progression-free survival.
The data update included 44 participants who received BNT211 at 4 dose levels of 1×106, 1×107, 1×108, and 1×108 with or without a regular, fixed dose of CARVac after lymphodepletion. These patients had germ cell tumors (n=16), ovarian cancer (n=17) and other solid tumor types (n=11). Investigators observed a dose-dependent increase in adverse events, with 52% (n = 23) of participants experiencing mostly grade 1 and 2 cytokine release syndrome (CRS). One patient had grade 3 CRS and 1 had grade 4 CRS. Two patients had mild or self-limiting neurotoxicity.1
- CARVac addresses challenges in solid tumor treatment by enhancing BNT211 CAR-T cell persistence.
- Dose-dependent adverse events were observed with BNT211 with around half of patients experiencing mostly mild CRS.
- The therapy had a 45% overall response rate (ORR) and a 74% disease control rate (DCR), with best efficacy in patients treated at dose level 2.
In 38 efficacy evaluable patients, ORR was 45% and DCR was 74%. Patients dosed below dose level 2 had an ORR of 11.1% and a DCR of 22.2% and patients dosed above dose level 2 had an ORR of 42.9% and a DCR of 71.4%.1 At dose level 2, 13 of 27 patients treated with or without CARVac had partial responses for an ORR of 59% and a DCR of 95%. Patients in this cohort received CARVac showed a prolonged persistence of CAR-T cells. Further dose expansion and exploration is required to select a recommended phase 2 dose for a trial in patients with germ cell tumors, which BioNTech expects to initiate in 2024.
“Toxicities at higher dose level led to further evaluation of safety via backfilling into several cohorts. CARVac improved CAR-T persistence, leading to sustained, ongoing detection up to 100 days in several patients at DL2. Backfilling to determine RP2D for CLDN6 CAR-T cells for a pivotal trial in germ cell tumors is currently ongoing,” Hannen said during his presentation.1
1. Haanen J. ESMO 2023 BioNTech data. Presented at ESMO Congress 2023; October 20-24; Madrid, Spain.
2. BioNTech Presents Positive Phase 1/2 Data Update for CAR-T Cell Therapy Candidate BNT211 in Advanced Solid Tumors at ESMO Congress 2023. News release. BioNTech. October 23, 2023. https://finance.yahoo.com/news/biontech-presents-positive-phase-1-153000750.html