FDA Grants Breakthrough Therapy Designation for Pimicotinib in TGCT

The FDA has granted a breakthrough therapy designation to pimicotinib (ABSK021) for the treatment of patients with tenosynovial giant cell tumor (TGCT) who are not amenable for surgery.

The agent is the first new-generation CSF-1R inhibitor to earn the designation, according to the drug developer, Abbisko Therapeutics.

“We are very pleased to learn that the FDA has granted pimicotinib the breakthrough therapy designation,” Xu Yao-Chang, PhD, chair and chief executive officer of Abbisko, said in a news release. “It will make our clinical development process and finished drug progress more efficient, which will help shorten the time to market and benefit patients worldwide as soon as possible.”

The designation is based on findings from the TGCT cohort of a phase 1, open-label study (NCT04192344) assessing the safety, tolerability, and pharmacokinetics (PK) of pimicotinib in patients with advanced solid tumors. Patients received a starting dose of 25 mg oral pimicotinib once daily in a “3+3” dose escalation fashion to establish maximum tolerated dose or a recommended dose of expansion.

Enrolled patients are being administered a single dose of pimicotinib on day –3, followed by 3 days off as a run-in period to access the safety and PK of a single dose of medication. Patients then continuously receive pimicotinib once daily in repeated 28-day cycles.²

Data from previous studies have shown that blocking the CSF-1R signaling pathway could effectively modulate and change macrophage functions, and potentially treat many macrophage-dependent human diseases. Pimicotinib is currently being investigated as a treatment for TGCT, as well as chronic graft-vs-host disease.

In findings from the phase 1 trial presented at the CTOS 2022 Annual Meeting, among 20 patients eligible for evaluation following treatment for TGCT in China, 74.0% remained on treatment for at least 3 months. The overall median duration of treatment was 105 days (range, 49-164).³

At week 13, the overall response rate (ORR) was 35% (95% CI, 15.4%-59.2%). Preliminary PK results showed that pimicotinib has a rapid absorption and relatively long elimination, a finding that supports daily dosing. Furthermore, investigators observed treatment notable pharmacodynamic marker changes, including induction of CSF1 and reduction of non-classical monocytes and C-terminal telopeptide.

Most treatment-emergent adverse effects were grade 1/2.

ORR was the primary end point. Secondary endpoints included overall tolerability, range of motion improvement, and patient-reported outcome of pain and stiffness. As of June 01, 2022, 27 Chinese patients with advanced TGCT were enrolled in phase 1b and treated with continuous oral dosing of 50 mg of daily pimicotinib.

References

1. Abbisko Therapeutics announces that US FDA has granted breakthrough therapy designation for its CSF-1R inhibitor pimicotinib (ABSK021). News release. Abbisko Therapeutics. January 29, 2022. Accessed January 30, 2023. https://bit.ly/3Hn0Vp1
2. A study to assess the safety, tolerability, and pharmacokinetics of ABSK-021 in patients with advanced solid tumor. Clinicaltrials.gov. December 10, 2019. Accessed January 30, 2023. https://bit.ly/3Y8qmRX
3. Xu H, Li B, Luo Y, et al. Preliminary phase 1b results of ABSK021 for advanced tenosynovial giant cell tumor: significant antitumor activity and favourable safety profile. Presented at CTOS 2022 Annual Meeting; November 16-19, 2022; Vancouver, BC. Abst P164.