ATG-022 Granted Orphan Drug Status by FDA for 2 Types of GI Cancer

The FDA has granted 2 orphan drug designations to ATG-022 for the treatment of gastric cancer and pancreatic cancer.¹

ATG-022 is a claudin 18.2 (CLDN18.2) antibody drug conjugate which has shown potent in vivo and in vitro antitumor efficacy in xenografts of patients with gastric cancer, including in subjects with low CLDN18.2-expression, according to findings presented at the American Association for Cancer Research (AACR) 2022 Annual Meeting.² The preclinical results demonstrated with ATG-022 suggested that its use would be a promising therapeutic strategy, and based on this hypothesis, an open-label, multicenter, phase 1 study was launched (CLINCH; NCT05718895).^2,3

“We believe that the orphan drug designation represents an important regulatory milestone for ATG-022, recognizing the significant and urgent unmet need for new treatments to help patients who are fighting difficult to treat and devastating diseases such as pancreatic and gastric cancers,” said Amily Zhang, MD, chief medical officer, Antengene Corporation Limited, in a press release. “We are enthusiastic about the potential for ATG-022 to treat gastric and pancreatic cancers. Moving forward, Antengene will work closely with regulators and clinical investigators to advance the CLINCH trial and fully assess ATG-022’s therapeutic potential for solid tumors.”

The CLINCH study will include approximately 156 patients with advanced or metastatic solid tumors.³ Sixteen to 36 of the patients enrolled will be treated during the dose-escalation phase, during which dosing will begin at 0.3 mg/kg every 3 weeks. The highest ATG-022 dose level to be investigated is 3.6 mg/kg. During the dose-expansion phase, approximately 120 patients with advanced/metastatic solid tumors and CLDN18.2 expression will be evaluated.

During CLINCH, investigators will primarily observe patients to determine the number of patients with dose-limiting toxicities, the maximum-tolerated dose of ATG-022, and the recommended phase 2 dose of the agent. The secondary end points of the study include progression-free survival, objective response rate, and duration of response. The study will also investigate preliminary overall survival.

Patients aged 18 years or older with histologically or cytologically confirmed advanced/metastatic solid tumors are eligible to enroll in the study given they have measurable disease, an estimated life expectancy of at least 12 weeks, and an ECOG performance status of 0 or 1. The study’s protocol requires patients to be willing to undergo biopsy at the time of screening, and to use contraception during the study. Female patients are also required to produce a negative pregnancy test prior to starting study treatment.

The study excludes patients who were previously exposed to a CLDN18.2 targeted therapy, had prior chemotherapy, immunotherapy, anticancer agents, or investigational drugs in another clinical trial within 28 days of the first dosing of ATG-022. In addition, patients who had a prior vaccination within 28 days of ATG-022 dosing, prior solid organ transplant, or have hypersensitivity to drugs with a similar chemical or biologic makeup of ATG-022 will be excluded from the study.

Individuals with primary central nervous system disorder, active infection, known history of immunodeficiency virus infection, an unresolved toxicity higher than grade 1, and/or other primary malignancies developed within 5 years prior to the first dose of the study drug are ineligible to enroll. Investigators may also exclude patients with complication or other conditions at their discretion.

_REFERENCES:

_{1. Antengene announces claudin 18.2 antibody-drug conjugate ATG-022 granted orphan drug designations by the U.S. FDA for the treatment of gastric and pancreatic cancers. News release. Antengene Corporation Limited. May 23, 2023. Accessed May 23, 2023. https://bit.ly/43EkRxh}

_{2. Chen P, Liu Y, Deng M, et al. Abstract 1143: ATG-022, an antibody-drug conjugate targeting Claudin 18.2, demonstrated potent in vivo efficacy in gastric cancer patient-derived xenografts. Cancer Res. 2022; 82 (suppl 12): 1143. doi:10.1158/1538-7445.AM2022-1143}

_{3. A study of ATG-022 in patients with advanced/metastatic solid Tumors (CLINCH). ClinicalTrials.gov. Updated February 8, 2023. Accessed May 23, 2023. https://clinicaltrials.gov/ct2/show/NCT05718895?term=ATG-022&draw=2&rank=1}