Pimicotinib Meets ORR End Point in Tenosynovial Giant Cell Tumor

Treatment with pimicotinib (ABSK021) led to a significant improvement in objective response rate (ORR) compared with placebo in patients with tenosynovial giant cell tumor (TGCT), meeting the primary end point of the phase 3 MANEUVER trial (NCT05804045).¹

Findings showed that patients treated with pimicotinib experienced an ORR at week 25 of 54.0% compared with 3.2% for those given placebo (P < .0001).

Statistically significant and clinically meaningful improvements in secondary end points were also observed for pimicotinib. The mean change in stiffness by Numeric Rating Scale (NRS) was –3.00 from baseline for the experimental arm vs –0.57 for the placebo arm (P < .0001). Mean change in pain by Brief Pain Inventory (BPI) was –2.32 vs 0.23 in the pimicotinib and placebo arms, respectively (P < .0001).

Additional efficacy and safety data from the study will be presented at an upcoming medical conference.

“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,” Niu Xiaohui, MD, director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital, stated in a news release. “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.”

MANUEVER was a 3-part, randomized, double-blind, placebo-controlled study that enrolled patients at least 18 years of age with histologically confirmed unresectable TGCT.2 Key inclusion criteria consisted of measurable disease per RECIST 1.1 criteria with at least one lesion of at least 2 cm; an ECOG performance status of 0 or 1; and adequate organ function and bone marrow function. Stiffness and pain scales needed to be completed during screening, and symptomatic disease because of active TGCT was required to meet the minimum requirements outlined in the study protocol.

Patients were excluded if they received previous treatment with highly selective CSF-1– or CSF-1R–targeted inhibitors; notably, previous treatment with imatinib (Gleevec) and nilotinib (Tasigna) was allowed. Other exclusion criteria consisted of known additional malignancies requiring active treatment; known metastatic TGCT; significant concomitant arthropathy in the affected joint, serious disease, or uncontrolled infection; and major surgery or previous antitumor therapy for TGCT within 4 weeks of randomization.

In the double-blind part 1 portion of the study, patients were randomly assigned in a 2:1 fashion to receive 50 mg of pimicotinib once per day (n = 63) or matching placebo (n = 31) for 24 weeks.¹ In part 2, eligible patients were allowed to continue treatment in an open-label expansion for up to an additional 24 weeks. Those who completed part 2 were allowed to continue in an open-label extension and safety follow-up in part 3.

ORR at week 25 per RECIST 1.1 criteria as assessed by blinded independent central review served as the trial’s primary end point. Secondary end points include tumor volume score, active range of motion, stiffness by NRS, pain by BPI, and physical function.

Safety data showed that pimicotinib was well-tolerated with a safety profile consistent with prior data. Instances of cholestatic hepatotoxicity were not reported. Treatment-emergent adverse effects led to treatment discontinuation and dose reduction in 1.6% and 7.9% of patients in the pimicotinib arm, respectively.

“Based on these new data from the MANEUVER study, together with once-daily oral administration that may promote long-term adherence and pimicotinib’s selective inhibition of CSF-1R, this investigational medicine has the potential to establish a new treatment paradigm for patients with TGCT,” Xiaohui said in the release.

References

1. Pimicotinib significantly improved outcomes for patients with tenosynovial giant cell tumor in a global phase III trial. News release. Merck KGaA. November 12, 2024. Accessed November 12, 2024. https://www.businesswire.com/news/home/20241111864964/en/Pimicotinib-Significantly-Improved-Outcomes-for-Patients-with-Tenosynovial-Giant-Cell-Tumor-in-a-Global-Phase-III-Trial
2. Study of pimicotinib (ABSK021) for tenosynovial giant cell tumor (MANEUVER). ClinicalTrials.gov. Updated August 29, 2024. Accessed November 12, 2024. https://clinicaltrials.gov/study/NCT05804045