Safety and efficacy of lacnotuzumab, a colony-stimulating factor 1 antibody for the treatment of tenosynovial giant cell tumors: a randomized phase II trial

Tenosynovial giant cell tumors (TGCT) are locally aggressive tumors that are often difficult to treat surgically due to their size and diffuse growth. Systemic therapies targeting the colony-stimulating factor-1 (CSF-1) pathway have emerged as alternatives. This study assessed the safety and efficacy of lacnotuzumab, a monoclonal antibody against CSF-1. This prospective, placebo-controlled, double-blind phase II study had three parts introduced sequentially: Part A: 7 participants received a single dose of lacnotuzumab (10 mg/kg) or placebo. Part B: 11 participants received 10 mg/kg lacnotuzumab or placebo for the first dose, followed by up to six monthly open-label doses (10 mg/kg). Part C: 18 participants were randomized to 3, 5, or 10 mg/kg lacnotuzumab for the first three doses, with possible escalation based on tumor response. Tumor volume was assessed by MRI every 4 weeks. Safety was monitored via laboratory assessments and adverse event (AE) reporting. The most frequent treatment-emergent AEs were periorbital/facial swelling (64%) and peripheral swelling (22%), mostly mild and self-limiting. Four weeks after a single dose, median tumor volume reductions were − 8.6% (3 mg/kg), -17.7% (5 mg/kg), and − 33.3% (10 mg/kg), versus − 10.1% for placebo. Eight weeks after the last dose, reductions were − 29.7% (3 mg/kg), -56% (5 mg/kg), and − 55.7% (10 mg/kg). Dose escalation further reduced tumor volume. Lacnotuzumab reduced TGCT volume, especially with multiple and higher doses. Edema was the most frequent AE but was self-limiting. While not curative in most cases, lacnotuzumab could be explored as neoadjuvant option to reduce tumor volume. Clinical trial number : ClinicalTrials.gov ID NCT01643850.