Pimicotinib Shows Promising Efficacy and Tolerability in TGCT

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Pimicotinib (ABSK021) led to an objective response rate (ORR) at week 25 of 54.0% in patients with tenosynovial giant cell tumor (TGCT) vs 3.2% for placebo (P <.0001) based on RECIST v1.1 per Blinded Independent Review Committee (BIRC), meeting the primary end point of the phase 3 MANEUVER study (NCT05804045).¹

The study also demonstrated statistically significant and clinically meaningful improvements in secondary end points. The mean reduction in stiffness, as measured by the Numeric Rating Scale (NRS), was -3.00 from baseline in the pimicotinib group, compared with -0.57 in the placebo group (P <.0001). Additionally, the mean reduction in pain, assessed by the Brief Pain Inventory (BPI), was -2.32 in the pimicotinib arm vs 0.23 in the placebo arm (P <.0001).

For safety, the MANEUVER study showed pimicotinib to be well tolerated with a safety profile consistent with previously reported findings. No evidence of cholestatic hepatotoxicity was observed in the study. Further, treatment-emergent adverse events (TEAEs) led to treatment discontinuation in 1.6% (n = 1) of patients treated with pimicotinib and dose reductions due to TEAEs were seen in 7.9% (n = 5) of patients given pimicotinib.

"TGCT tends to be a disease of the young. This rare, benign tumor that grows in and around the joints primarily affects young and middle-aged adults in their working years. The swelling, pain, stiffness and limited mobility caused by the disease can have a significant impact on the ability to perform daily activities, limiting patients' work and social lives. Treatment often involves surgery, yet the high recurrence rate and potential complications from repeated surgical interventions can be very challenging for patients to deal with, creating an urgent need for systemic therapy that could control tumor growth," said Niu Xiaohui, MD, director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital, in a news release.

Further efficacy and safety data from this study will be presented at an upcoming medical conference.

"Based on these new data from the MANEUVER study, together with once-daily oral administration that may promote long-term adherence and pimicotinib'sselective inhibition of CSF-1R, this investigational medicine has the potential to establish a new treatment paradigm for patients with TGCT," continued Xiaohui.

Methods and Design of the MANUEVER Trial

The 3-part, randomized, double-blind, placebo-controlled MANUEVER study evaluated treatment with pimicotinib in patients aged 18 years and older with histologically confirmed unresectable TGCT.²

Enrollment in the trial was open to patients with an ECOG performance status of 0 or 1, measurable disease per RECIST 1.1 criteria with 1 or more lesion of at least 2 cm, and adequate organ function and bone marrow function. Patients were also required to complete stiffness and pain assessments during the screening process, with symptomatic disease due to active TGCT needing to meet the minimum thresholds specified in the study protocol.

The double-blind, phase 1 portion of the study randomly assigned patients in a 2:1 ratio to receive either 50 mg of pimicotinib once daily (n = 63) or a matching placebo (n = 31) for 24 weeks. Phase 2 of the trial allowed eligible patients to continue treatment in an open-label expansion for up to an additional 24 weeks. Those who completed phase 2 were then permitted to enter phase 3, an open-label extension with safety follow-up.

The primary end point of the trial was ORR at week 25 per RECIST 1.1 criteria as assessed by BICR. Secondary end points consisted of tumor volume score, active range of motion, stiffness by NRS, pain by BPI, and physical function.

REFERENCES:

1. Pimicotinib significantly improved outcomes for patients with tenosynovial giant cell tumor in a global phase III trial. News release. Abbisko. November 11, 2024. Accessed November 13, 2024. https://tinyurl.com/245uhhh2

2. Study of pimicotinib (ABSK021) for tenosynovial giant cell tumor (MANEUVER). ClinicalTrials.gov. Updated August 29, 2024. Accessed November 13, 2024. https://clinicaltrials.gov/study/NCT05804045