The first patient has been dosed in Antengene‘s Phase 1 clinical trial investigating the dual inhibitor ATG-019, alone or in combination with niacin extended release, for people with non-Hodgkin’s lymphoma or advanced solid tumors.
ATG-019 is being developed as KPT-9274 by Karyopharm Therapeutics, but Antengene acquired its development and commercialization rights in several Asian countries and regions.
The TEACH trial (NCT04281420), taking place in Taiwan, follows the start of a similar Phase 1 trial (NCT02702492) in the U.S. by Karyopharm. Both trials are enrolling participants; more information is available here and here.
“We are pleased that the first patient of ATG-019 was successfully enrolled and dosed. This is our first step in developing PAK4/NAMPT dual-target inhibitor,” Jay Mei, founder, chairman, and CEO of Antengene, said in a press release.
ATG-019 is an oral small molecule that inhibits two proteins with an important role in cancer development: p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT).
PAK4 is a signaling protein that regulates a number of key cellular processes, but is overactive in some tumors, where it prevents immune cells from entering the tumor, and participates in tumor proliferation and metastasis.
NAMPT is an enzyme that helps cells produce enough energy for their daily functions. Cancer cells proliferate at higher rates and, thus, require more energy than healthy cells for their normal functioning.
By blocking both these proteins, ATG-019 may more effectively kill cancer cells by stopping a number of processes needed for their survival, including energy production, DNA repair, and proliferation.
Preclinical studies have demonstrated its activity against multiple tumor types, including breast cancer, multiple myeloma, and non-Hodgkin’s lymphomas.
TEACH is enrolling up to 70 participants who have failed, or refused, standard therapy and whose disease is currently progressing. The trial will first test ascending oral doses of ATG-019 to determine a maximum tolerated dose or an optimal dose for further testing. In this part, researchers will also examine how ATG-019 behaves in the body from absorption to excretion and what it does to the body.
Then, a second group of patients will receive the optimal dose, either alone or with daily niacin extended release (vitamin B3/nicotinic acid), which healthy cells use to produce energy in the absence of NAMPT.
In this part, patients will continue to be assessed for safety as well as for signs of efficacy, including their response rates, duration of response, time to disease worsening or death, and overall survival. Top-line results are expected in 2023.
“In addition to conducting the clinical trial for the treatment of advanced solid tumors and non-Hodgkin’s lymphoma, Antengene is also exploring the potential for ATG-019 in the treatment of different indications and in combination with existing regimens,” Mei said. “We hope to explore its potential from multiple dimensions in the near future.”
