(P 168) A PHASE 3 STUDY OF THE EFFICACY AND SAFETY OF PEXIDARTINIB IN ASIAN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR

Objective: Tenosynovial giant cell tumor (TGCT), a rare mesenchymal neoplasm of the synovium, bursae, or tendon sheath, is associated with overexpression of colony-stimulating factor 1 (CSF-1). Pexidartinib, a novel, orally administered, selective inhibitor of the CSF-1 receptor, is approved by the United States Food and Drug Administration and Korean and Taiwan authorities for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. This approval was based on the double-blind, randomized, placebo-controlled phase 3 ENLIVEN study (ClinicalTrials.gov identifier: NCT02371369) that demonstrated robust tumor response and improved symptoms and functional outcomes with pexidartinib compared to placebo in patients with symptomatic, locally advanced TGCT. The current study evaluated the efficacy and safety of pexidartinib in Asian patients with TGCT.

Methods: This multicenter, single-arm, phase 3 study in China and Taiwan (ClinicalTrials.gov identifier: NCT04488822) enrolled adult patients (≥18 years) with symptomatic TGCT associated with severe morbidity or functional limitation and not amenable to improvement with surgery. Patients received pexidartinib 400 mg (2 x 200 mg capsules) twice daily on an empty stomach. Pexidartinib was administered continuously on a 28-day treatment cycle until criteria for discontinuation was reached. The primary efficacy endpoint was overall response rate (ORR) defined as complete response (CR) or partial response (PR) by RECIST v1.1 at Week 25 by centrally reviewed MRI scans. Secondary endpoints included centrally reviewed ORR by tumor volume score (TVS) at Week 25, mean (standard error [SE]) change from baseline to Week 25 in range of motion (ROM) of affected joints, best overall response (CR or PR) by RECIST v1.1 and treatment-emergent adverse events (TEAEs). Data cutoff for the primary analysis was October 27, 2021, after all patients completed Week 25.

Results: Overall, 40 patients received pexidartinib. All patients were Asian; mean (standard deviation [SD]) age was 40.9 (12.05) years and 27 (67.5%) were female. Tumor response at Week 25 by RECIST v1.1 and TVS is shown in the Table. Overall least squares mean (SE) change from baseline at Week 25 in ROM was 23.05 (3.207; 95% CI: 16.40, 29.69), with improvement noted in the affected joint at Week 13 (15.64 [3.312]; 95% CI: 8.84, 22.44). Best overall response by RECIST v1.1 was observed in 12 (30.0%) patients, including 2 (5.0%) with CR; 20 (50.0%) patients had stable disease, and 1 (2.5%) patient had progressive disease. All patients reported TEAEs and were related to pexidartinib. NCI-CTCAE grade ≥3 TEAEs were reported in 16 (40.0%) patients, with 12 (30.0%) patients reporting treatment-related grade ≥3 TEAEs. There were no grade 5 TEAEs. The most common TEAE was hair color changes (31 [77.5%]), followed by increases in alanine aminotransferase (24 [60.0%]), aspartate aminotransferase (23 [57.5%]), and blood lactate dehydrogenase (19 [47.5%]); pruritus (19 [47.5%]); and rash and face edema (each 17 [42.5%]). Sixteen (40.0%) patients had AST ≥3 × ULN or ALT ≥3 × ULN, 9 (22.5%) patients had AST ≥5 × ULN or ALT ≥5 × ULN. Most of the events occurred within the first 2 study treatment cycles. There were 2 (5.0%) patients who had AST or ALT ≥ 3 × ULN with total bilirubin ≥2 × ULN.

Conclusion: In Asian patients with symptomatic TGCT not amenable to improvement with surgery, pexidartinib demonstrated clinical benefit in tumor response and improvement in joint function. The overall safety profile of pexidartinib was comparable with previous data. Hepatotoxicity was manageable with frequent liver test monitoring and dose modifications as defined in the protocol, and no new safety signals were observed in this Asian population.