Merck KGaA Reports Durable Tumor Control With Pimicotinib at Two Years

Merck KGaA reported two-year follow-up results from the Phase 3 MANEUVER study of pimicotinib, showing sustained improvements in pain, stiffness, joint mobility, and physical function alongside durable tumor responses in patients with tenosynovial giant cell tumor (TGCT). The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2026 on October 26.

The results provide longer-term evidence of clinical benefit with pimicotinib, an oral colony-stimulating factor 1 receptor (CSF-1R) inhibitor, in patients with TGCT who require systemic treatment and for whom surgery may cause substantial morbidity or functional limitations.

Sustained Improvements in Symptoms and Joint Function

Among patients initially randomized to pimicotinib, improvements in pain, stiffness, range of motion, and physical function were observed as early as Week 5 and were sustained through the follow-up period, with further improvements reported over time.

At Week 97, mean range of motion improved by 19.6% from baseline. Stiffness decreased by 3.9 points on the Worst Stiffness Numeric Rating Scale, while worst pain decreased by 3.1 points on the Brief Pain Inventory (BPI). Physical function improved by 7.4 points on the Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) scale.

Together, these findings suggest that the treatment’s potential benefit extends beyond tumor shrinkage to outcomes directly relevant to patients’ daily activities and joint function. However, the reported changes are within-group results and do not establish comparative benefit over placebo throughout the two-year period.

Tumor Responses Remained Durable at Two Years

The objective response rate (ORR), assessed by a blinded independent review committee using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was 76.2% (95% confidence interval [CI], 63.8%–86.0%). This was unchanged from the one-year analysis.

Using the tumor volume score (TVS), the ORR increased from 74.6% at one year to 77.8% at two years (95% CI, 65.5%–87.3%). RECIST v1.1 and TVS are distinct tumor-response assessment methods, so their results should be interpreted separately.

The median duration of response had not been reached at the time of analysis, indicating that the median time until response loss could not yet be determined. As of the March 1, 2026, data cutoff, median treatment duration was 22.6 months, ranging from 1.8 to 33.6 months. Fifty-four percent of patients initially randomized to pimicotinib remained on treatment at the two-year assessment.

The maintained RECIST response rate and unreached median duration of response support the durability of tumor control, although longer follow-up will be needed to characterize the duration of benefit more fully.

Safety and Tolerability

Pimicotinib’s safety profile was consistent with previous analyses. The announcement reported no evidence of cholestatic hepatotoxicity or hair and skin hypopigmentation.

During the initial randomized, double-blind treatment phase, treatment-emergent adverse events (TEAEs) leading to treatment discontinuation occurred in one patient receiving pimicotinib (1.6%). TEAEs resulting in dose reduction occurred in five patients (7.9%).

These findings provide additional safety information, but the discontinuation and dose-reduction figures relate specifically to the randomized treatment phase. They should not be interpreted as cumulative event rates across the entire two-year follow-up.

Phase 3 MANEUVER Study Design

MANEUVER (NCT05804045) is an ongoing, global, three-part, randomized, double-blind, placebo-controlled Phase 3 study evaluating pimicotinib in patients with TGCT who are eligible for systemic therapy and have not previously received CSF-1- or CSF-1R-targeted treatment.

The study enrolled 94 patients across the United States, Canada, Europe, and China. During Part 1, 63 patients received pimicotinib 50 mg once daily and 31 received placebo for 24 weeks. The primary endpoint was ORR at Week 25, assessed using RECIST v1.1 by a blinded independent review committee.

Secondary endpoints included TVS, range of motion, stiffness, pain, and physical function. Following the double-blind phase, eligible patients could enter Part 2, an open-label phase of up to 24 weeks of pimicotinib treatment. Participants completing Part 2 could subsequently enter Part 3, the open-label extension for continued treatment and safety follow-up.

Regulatory Status

Pimicotinib, also known as ABSK021, is an oral, selective small-molecule CSF-1R inhibitor developed by Abbisko Therapeutics. Merck holds worldwide commercialization rights.

According to the company, pimicotinib was approved in China in December 2025 and in Canada in June 2026 for adults with symptomatic TGCT when surgical resection could cause functional limitations or substantial morbidity. The drug has also received Breakthrough Therapy Designation from the US Food and Drug Administration and Priority Medicines (PRIME) designation from the European Medicines Agency. Regulatory applications remain under review in other jurisdictions, including the United States.

Clinical Implications

The two-year MANEUVER findings add evidence of sustained tumor response and improvements in symptoms and physical function with pimicotinib. The results are clinically relevant for patients who need systemic treatment, particularly when surgery carries substantial risks. Nevertheless, the open-label follow-up and absence of a continuing randomized comparator limit conclusions about comparative efficacy over two years. Further follow-up will help define the durability of benefit and longer-term safety.

Reference

Merck KGaA/EMD Serono, Two-Year Data of Pimicotinib Demonstrated Durable Tumor Control and Sustained Improvement in TGCT Symptoms and Joint Function, October 26, 2026.

Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER), ClinicalTrials.gov ID NCT05804045