KEY TAKEAWAYS
- The phase I trial aimed to report the safety and preliminary antitumor activity of pimicotinib in TGCT pts.
- The drug was given to TGCT pts who cannot have surgery at specified doses.
- The study found that pimicotinib was a promising new treatment for TGCT with significant antitumor activity and a favorable safety profile.
Tenosynovial giant cell tumor (TGCT) is a rare cancer caused by overexpression of colony-stimulating factor 1(CSF1) gene. Pimicotinib is a new drug that blocks CSF1R, a protein that helps TGCT cells grow. Pimicotinib has been granted Breakthrough Therapy Designation by the FDA for TGCT.
Researchers aimed to report the safety and preliminary antitumor activity of pimicotinib in TGCT patients(pts).
Pimicotinib was administered at 50 or 25 mg once daily in TGCT pts who cannot have surgery.
About 49 pts with TGCT were enrolled, including 37 pts treated with 50 mg QD and 12 pts with 25 mg QD. The median age was 39 years (range: 19-76), and 40.8% were male. The tumor location was mainly in the knee (53.1%), hip (18.4%), or ankle (12.2%). About 31 pts received at least one prior surgery, and 1 received prior exploratory systemic therapy (Anlotinib). Median treatment duration was 7.9 months (range: 0.4-12.5), and 89.8% remained on treatment. The ORR was 77.4% (24/31, including 2 CR) in 50 mg QD and 40% (4/10, including 1 CR) in 25 mg QD by IRC based on RECIST 1.1. Most responses were achieved within 25 weeks, and the median DOR in both cohorts was not reached. The average knee flexion range improvement at week 13 from baseline was 30.2 degrees (n = 13, range: 2, 105) in 50 mg QD and 4.8 degrees (n = 5, range: -12, 24) in 25 mg QD.
The results showed that at week 25, 66.7% (16/24) of the 50 mg once-daily (QD) group and 60% (3/5) of the 25 mg QD group were responders based on BPI-30, with a similar trend in stiffness. Most events were Grade 1 or 2, with four Grade 3/4 TEAEs, comprising 2 drug-related cases and 1 serious TEAE. Common TEAEs (≥20%) included LDH increase (75.5%), CPK increase (67.3%), α-HBDH increase (63.3%), AST increase (42.9%), amylase increase (26.5%), ALT increase (24.5%), pruritus (20.4%), and rash (20.4%). No serious adverse events(AEs) were reported, including hair color changes, severe liver issues, or CPK or transaminase elevations; 50 mg QD had twice the Cmax and Ctrough of 25 mg QD at steady state, consistent with earlier findings. Both groups exhibited significant pharmacodynamic changes, including increased plasma CSF-1 levels, reduced non-classical monocytes, and lower C-terminal telopeptide (CTx). Baseline changes in CSF-1 and CTx correlated with pimocetinib plasma levels.
The study found that Pimicotinib is a promising new treatment for tenosynovial giant cell tumor (TGCT) with significant antitumor activity and a favorable safety profile.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.11559#:~:text=
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04192344
Lu Yao, Yong Zhou, Binghao Li, Xianbiao Xie, Xinhui Du, Ting Yuan, Bo Chen, Qingping Zou, Qiuxiang Guo, Pan Liang, Chen Wang, Boyao Shan, Zhichao Tong, Yang Dong, Yao Weitao, Jingnan Shen, Zhaoming Ye, Chongqi Tu, and Xiaohui Niu. DOI: 10.1200/JCO.2023.41.16_suppl.11559 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 11559-11559.
