(P 169) UPDATED EFFICACY AND SAFETY PROFILE OF PIMICOTINIB (ABSK021) IN TENOSYNOVIAL GIANT CELL TUMOR (TGCT): 1-YEAR FOLLOW-UP FROM PHASE 1B

Objective: TGCT is a rare class of locally aggressive neoplasm, predominantly driven by overexpression of colony-stimulating factor 1 (CSF-1) gene. Pimicotinib, an orally administered selective small-molecule antagonist of CSF-1R, exhibits minimal inhibition of c-Kit and PDGFR. In 2023, the U.S. FDA conferred Breakthrough Therapy Designation and the European Medicines Agency granted Priority Medicine Designation upon Pimicotinib treatment of TGCT. Here, we report the phase 1b safety and efficacy results of Pimicotinib in TGCT patients (pts) over a 1-year follow-up.

Methods: The study (NCT04192344) entailed a TGCT cohort to evaluate the safety and preliminary antitumor activity of Pimicotinib in TGCT pts not amenable to surgical resection. The study investigated two dosage regimens: 50 mg once daily (QD) and 25 mg QD. As of 31 May 2023, a total of 56 TGCT pts were enrolled, comprising 44 pts in the 50 mg QD and 12 pts in the 25 mg QD cohort.

Results: Median age of 56 TGCT pts was 39 y (range: 18-76) and 41.1% were male. Tumors were primarily located in knee (48.2%), hip (16.1%) or ankle (10.7%). Prior to enrollment, thirty-three pts (58.9%) had undergone at least one tumor resection surgery. Extended follow-up indicated that Pimicotinib was well-tolerated, with a median treatment duration of 12.2 mos and the maximum treatment duration being 17.5 mos. 83.9% pts remained on treatment. A sustained improvement has been observed relative to the 6-month data earlier reported in CTOS last year, with an ORR of 87.5% (28/32, including 3 CR, 95%CI: 71.01%-96.49%) in 50 mg QD cohort and 66.7% (8/12, including 2 CR, 95%CI: 34.89%-90.08%) in 25 mg QD cohort by IRC based on RECIST 1.1 in response-evaluable analysis set. Out of the 16 pts in 50 mg QD cohort who achieved a PR within the first 6 mos and had follow-up data available, 15 of them (93.8%) sustained this response beyond 6 mos. Out of 5 pts in 50 mg QD cohort who achieved SD within the first 6 mos and had follow-up data, 4 (80%) pts improved to PR after 6 mos. Median DOR was not reached in either cohort. Durable improvements in range of motion, stiffness and pain over a 1-year follow-up were observed in both dose cohorts. The majority of TEAEs were Grade 1 to 2. Most common drug-related TEAEs (≥15%) include LDH increase (80.4%), CPK increase (67.9%), α-HBDH increase (62.5%), AST increase (42.9%), amylase increase (30.4%), ALT increase (25.0%), pruritus (21.4%), rash (19.6%), face oedema (19.6%) and dyslipidaemia (19.6%). No hair color change or serious liver injuries were reported, meanwhile, blood enzymes elevations were asymptomatic, within the expected range, and quickly recovered following drug interruptions, all of which were consistent with previous observations. Compared to the data within 6 mos, the overall safety profile remains largely consistent with no distinct adverse events emerging upon extended follow-up.

Conclusion: With the extension of treatment duration, there is an observed augmentation in the number of pts experiencing sustained tumor shrinkage and favorable safety of Pimicotinib with no apparent hepatotoxicity. Current data confers durable therapeutic benefits in TGCT pts, suggesting that prolonged exposure may represent an optimal treatment approach. In addition, a separate cohort with prior anti-CSF-1/CSF-1R therapies is underway to assess the safety and antitumor activity.