The U.S. Food and Drug Administration (FDA) has accepted Ascentage Pharma‘s Investigational New Drug (IND) application for APG-1387, allowing Ascentage to test the anti-cancer drug candidate in clinical trials.
APG-1387 is an inhibitor of a class of proteins called inhibitors of apoptosis (IAP) – a type of programmed cell death. It works by promoting cell death and preventing tumor growth and the spread of cancer cells to other locations.
“The acceptance of a U.S. IND application represents another important milestone in the global clinical development of APG-1387,” Dr. Yang Dajun, chairman and chief executive officer of Ascentage, said in a press release.
“Based on preclinical and clinical results achieved to date, we believe APG-1387 could represent a first-in-class treatment option for patients with a wide range of refractory or resistant cancers,” he added.
Unlike other IAP blockers – which are selective in their targets and bind exclusively to simple proteins, called monomers – APG-1387 binds and inhibits both monomers and dimers (the junction of two monomers).
Previous studies have shown that high levels of IAP proteins are often found in certain blood and solid cancers, such as melanoma, multiple myeloma, and cancers of the head and neck, breast, lung, and gastrointestinal tract.
The company completed Phase 1 trials in Australia and China testing escalating doses of APG-1387.
In the Australian trial (ACTRN12614000268640), a group of patients with advanced solid cancers or lymphoma began APG-1387 doses at 0.3 mg, administered intravenously for 30 minutes on days 1, 8, and 15, followed by one week off therapy, in 28-day cycles.
If the treatment was well tolerated after the first cycle, the dose was increased for subsequent patient groups up to the following doses: 0.6 mg, 1 mg, 1.5 mg, 2.5 mg, 4.0 mg, 7.0 mg, 12 mg, 20 mg, and 30 mg, accordingly. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal.
Last year, and supporting the drug’s efficacy, Ascentage published a study supporting APG-1387’s anti-tumor activity as a single agent in cells of nasopharyngeal carcinoma.
The study, “A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis,” appeared in the journal Cancer Letters.