Since project start in 2018, the CARAMBA consortium has made rapid progress in implementing the project and clinical trial. The manufacturing authorization for SLAMF7 CAR T was obtained in the 1st project period (PP) and is the first virus-free (i.e. independent from viral gene transfer vectors) CAR T manufacturing process in Europe that uses advanced SB transposon technology with mRNA and minicircle DNA vectors. This unique approach enables high scalable, cost-efficient CAR T manufacturing. The CARAMBA clinical trial received regulatory approval in all 4 intended EU member states - Germany, Spain, Italy, and France and is at present, the only academic investigator-initiated trial with CAR T cells that is active in several EU countries.
During the 4th PP, the site in France was initiated and started patient recruitment. In summary, since 2020, 11 patients have been recruited, of which 9 received SLAMF7 CAR T at increasing doses as foreseen in Phase I of the trial. Considering that several BCMA-directed therapies are concurrently being investigated in MM, patient selection and recruitment has been done prudently, carefully considering the potential benefits and risks of participating in the CARAMBA trial. Of note, CARAMBA is one of the few CAR T trials worldwide that considers MM patients that relapse after prior bone marrow transplantation.
In the CARAMBA trial, SLAMF7 CAR T treatment was well tolerated. The SLAMF7 CAR T cells engrafted after infusion and already show signs of clinical efficacy, even though the administered dose was still low. Of note, patients from all EU-countries are eligible and several patients have been enrolled that have their primary residence outside one of the EU member states represented in the CARAMBA consortium. Myeloma Patients Europe - the largest MM patient advocacy group in Europe is very active in the project and ensures that patient perspectives and concerns are being addressed. In the 3rd and 4th PP, several highly visible and impactful patient information and engagement campaigns were conducted, including videos and information materials in different languages. Significant output from the correlative research (including standardisation and continued quality control of laboratory procedures) and the exploratory research program was delivered. This includes several key note presentations and manuscripts in the world’s leading scientific journals. The CARAMBA consortium was highly active at international societies (EHA, EBMT, ESGCT) and conferences, including the EBMT & EHA European CAR T Cell Meeting as the largest CAR-T event world-wide (Chair 2022 – 2024: M. Hudecek). CARAMBA is also enabling the commercial development and exploitation of CAR T technologies in Europe through the biotech partner T-CURX that scoped the market space, established reimbursement and business development strategies and completed a first financing event in order to create a legacy for the CARAMBA project.
Conclusions: The CARAMBA consortium implemented its set project goals by bringing an innovative virus-free CAR-T product into the clinic. With the regulatory approval in 4 countries, MM patients from across the EU receive access to this new therapeutic approach. Although progress has been made in MM therapy with CAR-T directed against BCMA or GPRC5D both targets have been observed to be subject to antigen loss resulting in relapse of patients. Therefore and due to its much safer genomic insertion profile and reduced manufacturing costs compared to conventional CAR-T products, the interest in SLAMF7 CAR-T alone or as combinatorial target remains unwavering. The project has strengthened the collaboration among the European partners further, gained high visibility in the scientific community and serves with its scalable manufacturing as a platform for development of future CAR-T products in the EU. The aim is to continue the clinical trial after the project end to the product development towards the market and to enable commercial exploitation.
Key metrics: Trial approval in 4/4 EU member states. SLAMF7 CAR T product delivered to 9/9 patients. >100 CARAMBA project presentations at national, European and international conferences. >5 original papers published in excellent scientific journals. >4.000 followers on CARAMBA social media and website. >2.500 patients engaged at patient stakeholder events, conferences and outreach activities. >10 Mio EUR raised in additional public grant funding and private financing by CARAMBA partners during the project.
