Pimicotinib Significantly Improves Responses Vs Placebo in TGCT

The safety profile of pimicotinib in the MANEUVER trial (NCT05804045) was comparable with prior reports of the agent, and investigators highlighted no signs of cholestatic hepatoxicity.

The investigational CSF-1R inhibitor pimicotinib (ABSK021) reached the primary end point of objective response rate (ORR) among patients with tenosynovial giant cell tumor (TGCT), according to results from the phase 3 MANEUVER trial (NCT05804045).¹

At 25 weeks, the ORR was 54.0% with pimicotinib vs 3.2% with placebo, representing a significant improvement in response (P <.0001).

Data also showed statistically significant and clinically meaningful improvements in secondary end points related to patient outcomes in the pimicotinib arm. The mean change in stiffness by Numeric Rating Scale (NRS) from baseline was –3.00 with pimicotinib vs –0.57 with placebo (P <.0001). Additionally, the mean change in pain by Brief Pain Inventory (BPI) from baseline was –2.32 and 0.23 in each respective treatment arm (P <.0001).

The safety profile of pimicotinib in the MANEUVER trial was comparable with prior reports of the agent, and investigators highlighted no signs of cholestatic hepatoxicity. In the pimicotinib arm, 1.6% (n = 1) and 7.9% (n = 5) of patients experienced treatment-emergent adverse effects resulting in treatment discontinuation and dose reduction, respectively.

Investigators will present additional safety and efficacy findings from the MANEUVER trial at a future 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, professor and director of the Bone and Soft Tissue Tumor Diagnosis and Research Centre at Beijing Jishuitan Hospital, in Beijing, China stated in a news release.1 “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.”

In the 3-part, double-blind, randomized phase 3 MANEUVER trial, investigators are evaluating the efficacy and safety of pimicotinib vs placebo among patients with TGCT who are eligible for systemic therapy and have not previously received CSF-1– or CSF-1R–targeting therapy. In part 1 of the trial, 94 patients were randomly assigned 2:1 to receive pimicotinib at 50 mg once daily (n = 63) or matched placebo (n = 31) for 24 weeks. The trial includes patients who are receiving treatment in China (n = 45), Europe (n = 28), and the US and Canada (n = 21).

The trial’s primary end point is ORR at 25 weeks based on RECIST v1.1 criteria per blinded independent central review. Secondary end points include tumor volume score, active range of motion, stiffness by NRS, pain per BPI, and physical functioning measured by Patient-Reported Outcomes Measurement Information System (PROMIS) criteria.

Patients 18 years and older with histologically confirmed unresectable TGCT and measurable disease per RECIST v1.1 guidelines were eligible for enrollment on the trial.² Other eligibility criteria included an ECOG performance status of 0 or 1 and adequate organ and bone marrow function.

In January 2023, the FDA granted breakthrough therapy designation to pimicotinib as a treatment for those with TGCT.³ The designation was supported by findings from a phase 1b trial (NCT04192344). Pimicotinib has also received breakthrough therapy designation from the China National Medical Products Administration and priority medicine designation from the European Medicines Agency for the same patient population.

References

1. Pimicotinib significantly improved outcomes for patients with TGCT in phase III trial. News release. Merck KGaA. November 12, 2024. Accessed November 13, 2024. https://tinyurl.com/mtm5vrf9
2. Study of pimicotinib (ABSK021) for tenosynovial giant cell tumor (MANEUVER). ClinicalTrials.gov. Updated August 29, 2024. Accessed November 13, 2024. https://tinyurl.com/ynab32z9
3. Abbisko Therapeutics announces that US FDA has granted breakthrough therapy designation for its CSF-1R inhibitor pimicotinib (ABSK021). News release. Abbisko Therapeutics. January 30, 2023. Accessed November 13, 2024. http://bit.ly/3jk4TXr