ESMO 2023: LBA35
BioNTech’s innovative manufacturing process for CAR-T therapy, BNT211, has shown promising results in treating solid tumors. While the enhanced potency of BNT211 has demonstrated clinical activity and CAR-T cell persistence in solid tumor patients, it has also raised concerns about side effects. The European Society for Medical Oncology Congress featured data showing that BNT211, in combination with CARVac, BioNTech’s RNA vaccine.
The data update included 44 patients who were administered CLDN6 CAR-T cells at various dose levels, either alone or in combination with CARVac. These patients had different types of tumors, including germ cell tumors, ovarian cancer, and other solid tumor types. During the dose escalation process, adverse events increased in a dose-dependent manner, with 23 out of 44 patients experiencing cytokine release syndromes, primarily of grade 1 and 2, but with one grade 3 and one grade 4 event. Two patients exhibited mild and self-limiting neurotoxicity. Out of the 44 patients, 38 were evaluated for efficacy, showing an overall response rate (ORR) of 45% and a disease control rate (DCR) of 74%. Furthermore, 27 patients received CLDN6 CAR-T cells at a specific dose level (1×108 CAR-T cells) with or without CARVac, resulting in a 59% ORR and a 95% DCR, with those receiving CARVac showing prolonged CAR-T cell persistence in the same cohort.
These findings emphasize the potential of BioNTech’s BNT211 program. One of the aims of the ongoing Phase 1/2 trial is to determine the recommended dose for initiating a potential pivotal Phase 2 trial in patients with germ cell tumors, set to commence in 2024.
However, a dose-dependent increase in cytokine release syndrome (CRS), an immune response-related complication, was observed in 23 out of 44 patients, with most events being grades 1 and 2. The highest dose level led to one grade 4 CRS case, which involved acute respiratory distress syndrome but ultimately resulted in recovery. BioNTech is focusing on the second dose level, which demonstrates efficacy with manageable safety profiles.
“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. BNT211 aims to address two 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.”
– Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech
The manufacturing process improvements have made BNT211 more potent but also slightly more toxic. However, BioNTech is confident in its ability to manage toxicities and improve patient outcomes. The therapy aims to address solid tumors, a less explored field in CAR-T therapy. The data indicates lower neurotoxicity but increased liver toxicities due to the heightened cytokine production, activating the immune system and impacting organs.
BioNTech’s novel approach to CAR-T therapy may pave the way for effective solid tumor treatments, representing a significant step forward in the field of cancer therapeutics.
The data update from BioNTech’s CLDN6 CAR-T cell therapy trials shows promising results, with an overall response rate of 45% and a disease control rate of 74%. In a specific dose group, the ORR was 59%, and patients receiving CARVac demonstrated prolonged CAR-T cell persistence.
The durability of BNT211 remains a question, as CAR-T therapy often faces relapse issues. Redosing studies show promise in addressing this challenge. Regulatory discussions are ongoing to optimize trial designs and compare curative approaches to palliative care. BioNTech is planning to initiate the phase 2 portion of the trial, focusing on germ cell cancers in the EU and US, as it continues to expand its applications in the CAR-T field. Patients have reported an improved quality of life compared to previous chemotherapy, reinforcing the potential of BNT211 as a treatment option. These findings underscore the potential of BioNTech’s BNT211 program, with plans for a pivotal Phase 2 trial in patients with germ cell tumors in 2024.