Early Results Highlight Promise of Autologous CAR T-Cell Combination Therapy

The combination of SYNCAR-001and STK-009 exhibited favorable safety, efficacy, and chimeric antigen receptor (CAR) T-cell metrics in patients with relapsed or refractory mature CD19-positive hematologic malignancies, according to early phase I data published in Blood.

SYNCAR-001 is an autologous CAR T-cell therapy composed of a CD19-28z CAR and a mutated interleukin (IL)-2 receptor beta (hoRβ) that is paired with STK-009, “a pegylated IL-2 mutein that provides a selective IL-2 signal to hoRβ,” explained lead author, Maria Palomba, MD, of the Memorial Sloan Kettering Cancer Center.

The study used a standard 3+3 dose escalation design to evaluate the safety, efficacy, immunogenicity, and pharmacokinetics of SYNCAR-001 plus STK-009 for adults with relapsed or refractory mature CD19-positive hematologic malignancies.

SYNCAR-001 Plus STK-009 in CLL, MZL, DLBCL

This analysis included six patients in total: three with chronic lymphocytic leukemia (CLL), two with marginal zone lymphoma (MZL), and one with diffuse large B-cell lymphoma (DLBCL). The median age was 62.5 years (range, 56–70); the median number of prior therapies was four (range, 2–5); and four patients received bridging therapy.

Three patients received STK-009 at a dose of 1.5 mg and three received 3.0 mg. All six participants received a SYNCAR-001 dose of 30 × 10⁶ cells with lymphodepleting chemotherapy.

Reportedly, the majority of adverse events (AEs) were grade 2 or lower and nonserious. The authors observed no dose-limiting toxicities, and only two of the 11 serious AEs reported were judged to be related to SYNCAR-001 or STK-009. STK-009 alone did not affect biomarkers related to IL-2 or interferon gamma and no cytokine-related AEs were seen in the safety lead-in phase.

One patient with CLL and the patient with DLBCL had cytokine release syndrome (CRS) of grade 2 or lower. The patient with DLBCL also had immune effector cell–associated neurotoxicity syndrome (ICANS) of grade 1.

At the time of submission, the two patients with MZL had ongoing complete responses (CR) of 180 and 270 days, respectively. The patient with DLBCL had achieved ongoing CR of 90 days after undergoing bridging therapy. The three patients with CLL had disease progression by day 28, including one with Richter’s transformation on day 16.

The trial also enrolled a second cohort evaluating a SYNCAR-001 dose of 90 × 10⁶ without lymphodepleting chemotherapy, but no patients were treated by the time of publication.

“This is the first reported clinical and translational data of an orthogonal cytokine system that provides a selective IL-2 signal to CAR T cells,” wrote Dr. Palomba and colleagues.

Reference

Palomba ML, Caimi PF, Mei M, et al. A phase I study to evaluate the safety and tolerability of a combination autologous CD19 CAR T cell therapy (SYNCAR-001) and orthogonal IL-2 (STK-009) in subjects with relapsed or refractory CD19 expressing hematologic malignancies (NCT05665062). Blood 2024;144(suppl 1):3453. doi: https://doi.org/10.1182/blood-2024-202090