TJ107, an immuno-oncology agent also known as Hyleukin, is a T cell amplifier comprising a homodimer of engineered human interleukin-7 (IL-7) fused with Genexine’s proprietary long-acting platform hybrid Fc. IL-7 is a critical homeostatic factor for T cells, acting on T cells to increase their number, diversity and functionality.
TJ107 could play a pivotal role in reconstitution and reinvigoration of T cell immunity in cancer patients, providing unique opportunities for immuno-oncology combination strategies. The aim of this study (NCT04001075) is to determine the safety, tolerability and PKPD profile of TJ107 in Chinese cancer patients.
This ongoing study is to evaluate the safety, tolerability, PK profile, and anti-tumor activity of TJ107 in patients with advanced solid tumors who failed standard therapy. Patients receive TJ107 every 4 weeks by intramuscular (IM) injection. Dose escalation is aided by a 3+3 scheme from 240μg/kg to 1200μg/kg. A dose expansion cohort is being planned after the RP2D is determined. Safety is assessed by monitoring AEs and the associated grades per NCI CTCAE v5.0. Tumor response will be assessed per RECIST v1.1. Samples will be collected for PK, PD, ADA, immunophenotyping and TCR repertoire analysis.
Three patients with colorectal cancer were enrolled in the first cohort(240μg/kg).TJ107 was well tolerated and no DLTs were reported during the first cycle at this dose level. The preliminary PK results shows that TJ107 was rapidly absorbed and reached serum peak concentration around 24 hours post-dose. TJ107 was slowly cleared from the body and remained detectable in serum until Day 14 post-dose. A substantial increase in absolute lymphocyte count (ALC) from baseline was observed and peaked around 3 to 4 weeks post first dose. FACS analysis revealed increases in CD3+, CD4+ and CD8+ T cells. The numeric increase in T cells is consistent with increased Ki67 expression on Day 8 post first dose. There were no notable changes in B cells, monocytes, NK cells, neutrophils, nor Tregs, as expected.
Preliminary results from this trial suggest that TJ107 activated IL-7 pathway and expanded T cells in cancer patients in a similar way to data previously reported in healthy subjects. TJ107 exhibits a promising safety and tolerability profile in cancer patients under current dose. These findings support further clinical investigation.