Estrella Immunopharma’s Trial for CD19-Targeted T-cell Therapy EB103 in B-Cell Lymphomas Doses First Patient
The open-label, multicenter phase 1/2 STARLIGHT-1 study takes the form of a dose escalation trial with a 3+3 design.
The first patient has been dosed in Estrella Immunopharma’s phase 1/2 STARLIGHT-1 clinical trial (NCT06343311) for EB103, an investigational CD19-targeted T-cell therapy being evaluated for the treatment of B-cell lymphomas.1
EB103 is based on technology developed by Estrella’s parent company Eureka Therapeutics referred to as ARTEMIS. The ARTEMIS technology differs from traditional chimeric antigen receptor T-cell (CAR-T) technology in that it allows the T-cells to be activated via a pathway more similar to that seen in endogenous T-cell receptors.1,2 Notably, ARTEMIS T-cells are able to target intracellular cancer-specific antigens in addition to the surface-antigens typically used as targets for CAR-T.3 EB103 is autologous and targets CD19.
“Dosing our first patient in the STARLIGHT-1 phase 1/2 clinical trial is a significant milestone for EB103, " Cheng Liu, PhD, president and chief executive officer at Estrella, said in a statement.1 “We believe ARTEMIS T-cell therapy could offer unique advantages over current CAR-T therapies, including higher killing efficacy, improved T-cell persistence and a better safety profile. We look forward to unlocking its full potential in clinical settings.”
The open-label, multicenter STARLIGHT-1 study takes the form of a dose escalation trial with a 3+3 design. It is open to patients aged 18 years or older who have relapsed/refractory (r/r) B-cell nonHodgkin lymphoma (NHL). The initial dose escalation portion will treat around 6 patients in order to establish the recommended phase 2 dose (RP2D). Afterwards, the dose expansion portion may treat around 15 more patients at the RP2D. Beyond determining the RP2D, the trial’s primary end points are focused on safety, measuring the incidence of dose limiting toxicities during the first 28 days after treatment; the type, frequency, and severity of treatment-emergent adverse events during the first 90 days after treatment; and the type, frequency, and severity of treatment-emergent laboratory abnormalities during the first 90 days after treatment. On the other hand, secondary end points will include a number of oncology efficacy measures and assessments of pharmacokinetics. The investigational new drug application for STARLIGHT-1 was cleared by the FDA in March 2023.4
"CAR-T therapies have improved outcomes for patients with B-cell NHLs compared with traditional standard-of-care treatments,” Mehrdad Abedi, MD, a professor of medicine at UC Davis Comprehensive Cancer Center, added to the statement.1 “However, patients battling r/r NHL, especially those with high-risk conditions such as HIV-associated lymphoma, central nervous system lymphoma, and additional high-grade NHL subtypes urgently need new therapeutic options that minimize the risk of potential life-threatening side effects, including severe cytokine release syndrome and neurotoxicity. EB103 ARTEMIS T-cell therapy represents an innovative treatment option that may potentially benefit a wider range of r/r B-cell NHL patients.”
In addition to the STARLIGHT-1 trial, which will evaluate EB103 as a monotherapy, Estrella is also conducting preclinical research assessing the potential of EB103 in combination with its partner Imugene’s onCARlytics (CF33-CD19) oncolytic virus for the potential treatment of multiple solid tumor indications.2,4 onCARlytics is intended to induce expression of a truncated CD19 antigen on tumor cells in order to allow them to be targeted by CD19-directed T-cell therapies.5
Furthermore, Estrella is also conducting preclinical research on the potential of an ARTEMIS T-cell therapy to treat acute myeloid leukemia AML.3 The research demonstrated engineering of ARTEMIS T-cells with an antibody-T cell receptor that targets intracellular antigen Wilm's tumor 1 protein and a costimulatory signaling receptor directed at surface antigen CD33, 2 antigens highly expressed on the majority of AML cells.
"ARTEMIS technology can unlock the potential of adoptive T-cell therapies by targeting intracellular proteins that are presently not druggable by conventional antibodies or conventional CAR T-cells that target only cell surface proteins, and we remain committed to rapidly advancing our technology in the field of oncology,” Liu said in a January 2024 statement.3
