ST Pharm's phase 1 study of anticancer drug basroparib shows safety at ESMO 2024

ST Pharm said it presented the detailed results of its phase 1 clinical trial for basroparib (STP1002), a tankyrase-targeting anticancer drug, at the European Society for Medical Oncology (ESMO) Congress 2024, held in Barcelona, Spain from Sept. 13 to 17.

The ESMO Congress is a leading global academic event for advancing cancer research, treatment, and patient care, attracting around 34,000 attendees from 149 countries.

Basroparib is the first compound globally to complete human clinical trials for its selective inhibition of tankyrase 1/2. Competing drugs targeting the same mechanism failed in preclinical stages due to gastrointestinal toxicity.

The phase 1 trial was an open-label, multicenter, dose-escalation study aimed at evaluating the safety, tolerability, and pharmacokinetics (PK) of basroparib in patients with advanced solid tumors. It also sought to determine the maximum tolerated dose (MTD).

A total of 25 patients participated in the trial, including 23 with colorectal cancer and 2 with renal cancer. The drug was administered orally once daily in doses ranging from 30 mg to 360 mg across seven dose levels, with a 28-day cycle (21 days of administration followed by seven days of rest).

In terms of safety, most of the 25 treatment-related adverse events (TRAEs) observed were mild (Grade 1-2), such as fatigue and nausea. There were four cases of Grade 3 or higher adverse events, including one instance of Grade 3 pancreatitis and three cases of Grade 4 adverse events -- elevated amylase, elevated lipase, and hypercalcemia.

Still, the company stressed that it reported no clinically significant adverse events were observed in laboratory tests, physical examinations, vital signs, or electrocardiogram evaluations. Also, no bone-related side effects were reported.

Antitumor efficacy was evaluated in 17 patients, with four demonstrating stable disease (SD). Pharmacokinetic analysis showed a dose-dependent increase in drug exposure, with a half-life of approximately six to seven hours. Although dose-limiting toxicity was not observed during the trial, the Safety Monitoring Committee (SMC) concluded, based on statistical analyses and pharmacokinetic data, that the MTD and the recommended dose for phase 2 trials would be set at 360 mg.

"The phase 1 trial has demonstrated excellent safety and tolerability for basroparib, which paves the way for combination strategies with other therapies, such as MEK inhibitors, chemotherapy, and immunotherapy,” said Christopher H. Lieu, a professor at the University of Colorado Cancer Center and principal investigator of the study.

An ST Pharm spokesperson also said, “It is well known that administering tankyrase inhibitors alone is not expected to yield strong anticancer effects, but preclinical results have shown that combined therapy can enhance the anticancer effect."

So far, the only drug that has entered clinical stages with the mechanism of selectively inhibiting tankyrase is basroparib, he added.

The official stressed that as the phase 1 clinical trial has demonstrated excellent safety and tolerability, the company plans to establish strategies for subsequent clinical trials while simultaneously actively pursuing technology transfer.