Gene-Editing Clinical Trial Update

FT538: An Off-The-Shelf Natural Killer Cell Therapy for Acute Myeloid Leukaemia and Multiple Myeloma

FT538 is a universal, off-the-shelf natural killer (NK) cell cancer immunotherapy that is being developed by Californian biopharmaceutical company Fate Therapeutics.

The novel therapy is being tested in two separate treatment regimens in a Phase 1 dose-finding study; either as monotherapy for acute myeloid leukaemia (AML) or as combination therapy with monoclonal antibodies for multiple myeloma (MM).

The study, which aims to enrol up to 105 adult participants, will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts. The dose-escalation stage aims to determine the maximum tolerated dose (MTD) of up to three doses of FT538 at set intervals during the treatment period for the two separate regimens mentioned above. During dose-expansion, the safety, efficacy, and pharmacokinetics of FT538 will be further characterised in all regimens.

FT819: An Off-The-Shelf CAR T-Cell Therapy for B-Cell Malignancies

In a recent IND update, we shared that Fate Therapeutics was developing FT819, an off-the-shelf CAR T-cell cancer immunotherapy candidate for the treatment of acute lymphoblastic leukaemia (ALL).

Since then, Fate Therapeutics has initiated a Phase I dose-finding study for FT819 as monotherapy and in combination with IL-2 in participants with relapsed/refractory B-cell malignancies including B cell lymphoma, chronic lymphocytic leukaemia (CLL) and precursor B-cell ALL (B-ALL). The study comprises a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts. The trial aims to enrol up to 297 adult participants with an estimated primary completion date in December 2022.

FT819 is CRISPR-engineered to express a novel 1XX CAR that targets the CD19 B cell-specific cell-surface antigen that is expressed in all B cell lineage cancers. The company presented encouraging in vivo pre-clinical data at last year’s American Society of Hemoatology Meeting, and obtained IND clearance from the FDA in July of this year, allowing it to proceed with the clinical development of FT819 for CD19+ cancers.

FT819 is the first-ever CAR T-cell therapy to be derived from a clonal master iPSC line engineered with Fate Therapeutic's proprietary iPSC platform, and it has several first-of-kind features that are designed to improve the safety and efficacy of CAR T-cell therapy.

CB-010: An Off-The-Shelf Allogeneic CAR-T Cell Therapy for B Cell Non-Hodgkin Lymphoma

Caribou Biosciences, a genome-editing company based in Berkeley, California, is developing CB-010 as an off-the-shelf allogeneic anti-CD19 CAR-T cell therapy for relapsed/refractory B cell non-Hodgkin lymphoma.

CB-010 is Caribou’s most advanced cell therapy candidate and is derived from healthy donor T cells that are genome-edited using Caribou’s next-generation CRISPR-Cas technology that is based on CRISPR hybrid RNA-DNA (chRDNAs). Using CRISPR, the PD-1 gene is deleted from CAR-T cells. This gene encodes the PD-1 protein which functions as a safety switch on T cells that cancer cells turn on to protect themselves from T cell-mediated immune responses.