Off-the-Shelf TRX103 Exhibits Early Tolerability in Select HCT Populations

Treatment with TRX103, an allogenic Tr1 cell product, exhibited manageable safety and dose-dependent exposure, expansion, and persistence in a small cohort of patients with hematologic malignancies undergoing HLA-mismatched hematopoietic cell transplantation (HCT), according to findings from a presentation given at the 2026 Tandem Meetings.

Specifically, among 12 patients who underwent TRX103 infusion, no dose-limiting toxicities (DLTs) were observed by day 28 of treatment. Moreover, no serious adverse effects (SAEs) were observed related to TRX103 infusion in this population, with 2 patients experiencing a grade 1 infusion reaction and transient rash, respectively. Hematopoietic stem cell transplantation (HSCT) engraftment was initiated in all patients, with a median time to neutrophil engraftment of 17 days (range, 14-31) and 100% donor chimerism at a median of 32 days (range, 28-36).

Moreover, 5 patients experienced grade 2 to 4 acute graft-versus-host disease (GVHD), with grade 2 events occurring in 2 patients, 1 patient, and 1 patient at dose levels 1, 3, and 4, respectively, as well as 1 patient in dose level 3 experiencing a grade 4 acute GVHD event. Regarding severity, 2 patients experienced mild chronic GVHD at dose levels 1 and 3, 1 patient experienced moderate chronic GVHD at dose level 3, and 1 patient experienced severe chronic GVHD at dose level 1.

Preliminary clinical data revealed that complications due to underlying disease were the most prominent at the lowest dose levels. A total of 3 patients experienced disease relapse, including 2 patients with acute myeloid leukemia (AML) in the first and second dose levels, respectively, at day +120 and +210. One patient treated at dose level 4 with B-cell acute lymphoblastic leukemia (B-ALL) experienced a relapse at day +85. Additionally, 1 death was observed at day +72 due to respiratory failure, but it was deemed unattributable to TRX103.

“[There was] no DLT at day 28 after using the [TRX] cells. Engraftment was confirmed in all patients with no issue,” Monzr Al Malki, MD, director of the Unrelated Donor Bone Marrow Transplant and Haploidentical Transplant Programs and associate professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, said in his presentation of the study data. “No SAEs related to the cells themselves [were observed]. There was one [infusion-related reaction] at the [225 x 10⁶] dose.”

Patients selected for enrollment on the study had B- or T-cell ALL, AML, myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). They were also undergoing HLA-mismatched related or unrelated hematopoietic peripheral blood stem cell transplantation (PBSCT).

Screening occurred 35 to 8 days before study treatment, wherein cohort dose level assignments for TRX were determined. Patients underwent conditioning on days –7 to –1, and HSCT infusion was given on day 0 of study treatment. GVHD prophylaxis was provided on days 3 and 4 of study treatment, TRX103 was infused on day 6 of study treatment, and a DLT evaluation window was conducted from day 6 to 34 of study treatment.

In addition, patients received mycophenolate mofetil (MMF) or sirolimus (Rapamune). Sirolimus was given starting on day 5 of study treatment at a loading dose of 4 to 6 mg, followed by 1 to 2 mg daily, which tapered from day 60 to 90 and was discontinued between days 100 and 150. MMF was initiated day 5 at a dose of 3 g or less daily, with patients discontinuing the agent between days 28 and 35 of study treatment.

The study followed a modified 3+3+3 design, and the respective dose levels in each cohort for the escalation portion of the trial were 25 x 10⁶, 75 x 10⁶, 225 x 10⁶, and 675 x 10⁶ DRX cells. Patients in the expansion cohort will be treated at recommended dose levels determined by a safety review committee (SRC) evaluation.

The trial included 1 patient with CMML, 3 with MDS, 4 with B-ALL, and 4 with AML. Two patients received myeloablative conditioning, and 10 received reduced-intensity conditioning. The median age at the time of PBSCT was 66 years (range, 37-73).

Moreover, there was a total of 8 haploidentical and 4 HLA-mismatched unrelated donor transplants in this patient group. The median number of infused CD34-positive cells was 5.02 x 10⁶ cells/kg (range, 4.05-8.06), and the median nucleated cell total was 4.84 x 10⁸cells/kg (range, 1.39-18.58).

The primary end points of the trial were the safety and tolerability of TRX103. Secondary end points included incidence of grade 2 to 4 acute GVHD, incidence and severity of chronic GVHD, and 1-year overall survival. Exploratory objectives included pharmacokinetics and pharmacodynamics, time to immune reconstitution, and incidence of 1-year GVHD-free relapse-free survival.

Disclosures: Al Malki disclosed having received research funding from Miltenyi Biotec, Orca Bio, Stemline Therapeutics, Takada, and Incyte; serving in advisory committees for Hasna Biopharma, Gilead, Gamida Cell, and Incyte; and serving in a consultancy role for Tscan, TrX1 Inc., Ossium Health, Cellkure, MaaT, and CareDx.

Reference

Al Malki MM, Juckett M, Perales MA, et al. Off-the-shelf engineered Tr1 cells (TRX103) in patients with hematological malignancies undergoing HLA-mismatched hematopoietic cell transplantation (HCT) show safety and dose dependent effects. Presented at: 2026 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 4-7, 2026; Salt Lake City, UT. Abstract 8