SCRI-CAR19 / Seattle Children's Hospital - LARVOL DELTA

Outcomes of PLAT-02 and PLAT-03: Evaluating CD19 CAR T-Cell Therapy and CD19-expressing T-APC Support in Pediatric B-ALL. (PubMed, Blood) - P1, P1/2 | "This study reports outcomes of PLAT-02, a phase 2 trial of SCRI-CAR19, a second-generation CAR T-cell product with FMC63 scFv and 41BB costimulation, in pediatric and young adult patients with B-cell acute lymphoblastic leukemia; and PLAT-03, a companion study evaluating exogenous CD19 antigen stimulation with serial infusions of T cells expressing truncated CD19, T-cell antigen presenting cells (T-APCs). The efficacy cohort of PLAT-02 (n=72 patients, median age 12.5 years) received fludarabine/cyclophosphamide lymphodepletion followed by a dose of 1X106 CAR+ T cells/kg...Further exploration of serial artificial CD19 antigen exposure is warranted based on these pilot results. PLAT-02 (NCT02028455) and PLAT-03 (NCT03186118)."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD19

Feasibility and Favorable Responses Following Investigational CAR T-Cell Therapy for Relapsed and Refractory Infant ALL. (PubMed, Blood Adv) - "We describe our experience utilizing two experimental CD19-CAR T-cell products, SCRI-CAR19 or SCRI-CAR19x22, for 19 patients with R/R infant B-ALL enrolled on three clinical trials...Neurotoxicity occurred in 2/17 (11.8%) patients with all events ≤ Grade 2. With the successful early clinical experience of CAR T-cell therapy in this population, more systematic evaluation specific to infant ALL is warranted."

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Childhood B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

A Phase 2 Trial of SCRI-CAR19 Demonstrates Favorable Leukemia-Free Survival (LFS), with a Pilot Study of CD19-Expressing T-Cell Antigen Presenting Cells (CD19t T-APCs) Demonstrating Safety and Tolerability (ASH 2023) - P1, P1/2 | "The primary efficacy cohort was defined as those who received fludarabine/cyclophosphamide (flu/cy) LD and were infused with CAR19. However, subjects were not randomized to receive T-APCs and those enrolled on PLAT-03 were more heavily treated and more likely to have received a prior HCT. Further exploration of T-APCs is warranted to define and evaluate their impact on persistence and durable responses."

Clinical • P2 data • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Neutropenia • Oncology • Transplantation • CD19

Molecular Characteristics of Resistance to CD19-Directed CAR T Cells Revealed in Pediatric ALL (Cancer Network) - P1/2 | N=167 | NCT02028455 | "The investigators used bone marrow samples from 14 participants in the PLAT-02 trial (NCT02028455) of CD19-directed CAR T-cell therapy for relapsed/refractory pediatric ALL...In patients who went on to have PNR, investigators discovered epigenetic markers including 238 regions of hypermethylated DNA, which is associated with inactivated genes (P = 8.15 × 10-25). These regions are known to be activated in stem cells....The ATAC-seq analysis showed increased accessibility of chromatin at regions linked to stem cell proliferation (normalized enrichment score [NES] = 2.31; P < .0001) and cell cycling (NES = 2.27; P < .0001), indicating inherent plasticity that may allow leukemia cells to adapt to resist CAR T-cell therapy."

Biomarker • P1/2 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology