Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

• Published in: The Lancet (British edition) 2024-06, Vol.403 (10445), p.2709-2719
• Main Authors: Gelderblom, Hans, Bhadri, Vivek, Stacchiotti, Silvia, Bauer, Sebastian, Wagner, Andrew J, van de Sande, Michiel, Bernthal, Nicholas M, López Pousa, Antonio, Razak, Albiruni Abdul, Italiano, Antoine, Ahmed, Mahbubl, Le Cesne, Axel, Tinoco, Gabriel, Boye, Kjetil, Martín-Broto, Javier, Palmerini, Emanuela, Tafuto, Salvatore, Pratap, Sarah, Powers, Benjamin C, Reichardt, Peter, Casado Herráez, Antonio, Rutkowski, Piotr, Tait, Christopher, Zarins, Fiona, Harrow, Brooke, Sharma, Maitreyi G, Ruiz-Soto, Rodrigo, Sherman, Matthew L, Blay, Jean-Yves, Tap, William D, Loong, Herbert, Brunello, Antonella, Krieg, Andreas, Algulnik, Mark, Riedel, Richard, Okuno, Scott, Loggers, Elizabeth, Alcindor, Thierry, Ferraresi, Virginia, Serrano, César, Randall, R. Lor, Wilky, Breelyn, Ravi, Vinod
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analgesics; Anilides; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Clinical outcomes; Creatine; Creatine kinase; Double-Blind Method; Drug dosages; Female; Giant Cell Tumor of Tendon Sheath - drug therapy; Health services; Hepatotoxicity; Humans; Kinases; Male; Middle Aged; Morbidity; Narcotics; Patients; Placebos; Quality of life; Questionnaires; Quinolines; Range of motion; Regulatory approval; Response rates; Solid tumors; Statistical analysis; Surgery; Treatment Outcome; Tumors
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(24)00885-7

Tenosynovial giant cell tumour (TGCT) is a locally aggressive neoplasm for which few systemic treatment options exist. This study evaluated the efficacy and safety of vimseltinib, an oral, switch-control, CSF1R inhibitor, in patients with symptomatic TGCT not amenable to surgery. MOTION is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 35 specialised hospitals in 13 countries. Eligible patients were adults (aged ≥18 years) with a histologically confirmed diagnosis of TGCT for which surgical resection could potentially worsen functional limitation or cause severe morbidity. Patients were randomly assigned (2:1) with interactive response technology to vimseltinib (30 mg orally twice weekly) or placebo, administrated in 28-day cycles for 24 weeks. Patients and site personnel were masked to treatment assignment until week 25, unless progressive disease was confirmed earlier. The primary endpoint was objective response rate by independent radiological review using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) at week 25 in the intention-to-treat population. Safety was assessed in all patients who received the study drug. The trial is registered with ClinicalTrials.gov, NCT05059262, and enrolment is complete. Between Jan 21, 2022, and Feb 21, 2023, 123 patients were randomly assigned (83 to vimseltinib and 40 to placebo). 73 (59%) patients were female and 50 (41%) were male. Nine (11%) of 83 patients assigned to vimseltinib and five (13%) of 40 patients assigned to placebo discontinued treatment before week 25; one patient in the placebo group did not receive any study drug. Objective response rate per RECIST was 40% (33 of 83 patients) in the vimseltinib group vs 0% (none of 40) in the placebo group (difference 40% [95% CI 29–51]; p