FDA accepts Investigational New Drug application for PBCAR19B for the treatment of R/R NHL

On January 19, 2021, it was announced that the U.S. Food and Drug Administration (FDA), accepted the Investigational New Drug application for PBCAR19B, a next-generation, allogeneic CD19 chimeric antigen receptor (CAR) T‑cell candidate for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). This was based on preclinical data that showed PBCAR19B delays allogeneic rejection mediated by T cells and natural killer cells. This acceptance allows for the commencement of a phase I trial (NCT04649112).¹

PBCAR19B¹

Allogeneic anti‑CD19 CAR T‑cell therapy with an added stealth vector for a short hairpin RNA, which suppresses the expression of the beta-2 microglobulin component of major histocompatibility complex class I (MHC‑I), thus making the cells less visible to cytotoxic T cells. The vector also carries an HLA‑E gene to inhibit the cytotoxic activity of natural killer cells that may be stimulated by reduced MHC‑I expression.

NCT04649112^1,2

• A non-randomized, open-label, single-dose, dose-escalation, and dose-expansion study to evaluate the efficacy and safety of PBCAR19B at increasing flat dose levels (2.7 × 10⁸–8.1 × 10⁸ CAR T‑cells) in patients with R/R NHL.
• Primary outcome measures: maximum tolerated dose and dose-limiting toxicities.
• Secondary outcome measures: duration of response, objective response rate, progression‑free survival, and overall survival.
• Estimated start date: May 3, 2021.