FDA Grants Orphan Drug Designation to ATG-101 for Pancreatic Cancer

Patients with pancreatic cancer may benefit from treatment with ATG-101, which was granted orphan drug designation by the FDA.

The novel PD-L1/4-1BB bispecific antibody ATG-101 has received orphan drug designation from the FDA for patients with pancreatic cancer, according to a press release from Antengene Corporation.

The designation will aid in the company’s communication with the FDA to accelerate clinical trial development and the eventual registration of the agent. Currently, there has not been any global approval of a PD-L1/4-1BB bispecific antibody for patients with pancreatic cancer. In preclinical studies, ATG-101 has yielded significant anti-tumor activity in animal models with resistant tumors or who had progressive disease following anti–PD-1 and –PD-L1 therapy. The agent has also demonstrated a promising safety profile, according to Good Laboratory Practice toxicology studies.

It is the first PD-L1/4-1BB bispecific to enter development in Australia in addition to being assessed in China and the United States.

“We are very encouraged by this orphan drug designation from the U.S. FDA and are hopeful that ATG-101 will offer a novel therapeutic to patients with pancreatic cancer. As Antengene's first in-house developed asset with global rights, ATG-101 has already entered clinical development in Australia, China, and the U.S. We will strive to accelerate the global clinical development of ATG-101 in efforts to provide a new treatment option to patients around the world,” Bo Shan, PhD, chief scientific officer at Antengene, said in a press release.

ATG-101 was designed to block immunosuppressive PD-L1 binding and yield conditional 4-1BB stimulation. By doing so, the agent prompts anti-tumor immune effectors and yields enhanced anti-tumor activity with a manageable safety profile.

The agent is currently being assessed as part of the phase 1 PROBE study (NCT04986865), which includes patients with metastatic and advanced solid malignancies and mature B-cell non-Hodgkin lymphomas. The first-in-human study has an estimated enrollment of 482 patients and will include a dose escalation phase and a dose expansion phase. Intravenous ATG-101 will be administered once every 21 days, and the dosing levels will be chosen based on the starting dose.

The primary outcome measures are safety, serious adverse effects (AEs), and dose-limiting toxicities. Secondary outcomes include overall response rate, duration of response, disease control rate, progression-free survival, and overall survival.

To be included in the study patients need to be aged 18 years or older with a histologically or cytologically confirmed solid malignancy that has progressed on standard therapy, is intolerant to standard therapy, or for which standard therapy would not be adequate. Other inclusion criteria include an estimated life expectancy of at least 12 weeks, an ECOG performance status of 0 or 1, and adequate contraceptive measures in patients of all sexes.

Those with known central nervous system metastases, prior administration of ATG-101 or a 4-1BB agonist, prior anti-tumor therapy within 21 days, or wide field radiotherapy within 28 days were excluded from the trial.


FDA news release. Antengene Announces ATG-101 Granted Orphan Drug Designation by the U.S. Published: September 18, 2022. https://prn.to/3qWyoig. Accessed: September 21, 2022.