PB2000: LESSONS LEARNED FROM CERBA RESEARCH CHIMERIC ANTIGEN RECEPTOR T-CELL (CAR T) MULTIPLE MYELOMA RUNNING TRIALS

Abstract

Background: The pipeline has 359 liquid tumor trials that are CAR T driven where Cerba Research (CR) understands that there is a demand to provide innovative specialty testing, such as flow cytometry, sequencing and downstream biomarker analysis. Herein, CR examined 38 of our active multiple myeloma (MM) trials since 2016 with a focus on CAR T therapy. We identified 15 of those trials where CR participated as a central laboratory. Aims: The aim of this evaluation is to identify gaps within current CAR T MM trial endpoints and to improve for the future of our liquid tumor trials. Methods: We analyzed internal trial matrix database and examined other documents such as laboratory specification documents, trial design, protocol, and schedule of activities. We used descriptive statistics to illustrate our specialty testing involvement and to identify gaps in our offerings. Results: CR currently has 38 running MM trials, in which 15 (39%) have a CAR T therapy. Sixteen (42%) of our MM trials are phase I/first-in-human (FIH), whereas 14 (37%) and 7 (18%) are phase II and III, respectively. Within our MM CAR T trials, we perform flow cytometry (FCM) in 87% of cases. Our involvement in FCM is exploratory in nature, and the design of the panels is performed with continued scientific discussions with sponsors. Some of the flow cytometry panels performed in our CAR T trials are: - Enumeration of CAR T cells in whole blood and bone marrow aspirates, including PK evaluation - Immunophenotyping of CAR T cells (memory, regulatory, activation status, exhaustion status) - Minimal residual disease (MRD) CR is often involved across full CAR T programs starting at FIH up to registration trials. We have robust upstream capabilities where we perform peripheral blood mononuclear cell (PBMC) isolation (60%), bone marrow mononuclear cell (BMMC) isolation (53%), DNA extraction (47%), cell sorting (53%), serum and urine protein electrophoresis/immunofixation (47%), and histopathology (decalcification, embedding, sectioning) (53%). We are also involved in routine testing such as hematology (27%), biochemistry (33%) and coagulation (27%). However, except for FCM (87%), immunohistochemistry (IHC 47%) and FISH (47%), we identified a gap in requests for sequencing within MM CAR T trials (0%.) Next generation sequencing (NGS), which was mostly for MRD assessment, was performed by referral labs. We also identified up to 11 referral labs participating in MM trials which significantly adds to a trial operation complexity. Summary/Conclusion: CR currently has strong FCM fit-for-purpose design and execution capabilities as demonstrated by our participation in CAR T programs as a central laboratory. Using FCM in CAR T trials is important as it can aid in determining effectiveness of therapy, any potential side effects, and general health of the immune system by performing longitudinal monitoring of the immune system. We also frequently isolate PBMCs/BMMCs, extract DNA and perform histopathology on a global scale for clinical trial purposes. Herein, we determined that we have good downstream efforts with FCM, IHC and FISH and plan on growing NGS offerings by creating a new MRD NGS oncopanel and compare it with FCM for validation and concordance in multiple myeloma.