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

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 multice...

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Published in:The Lancet (British edition) Vol. 403; no. 10445; pp. 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: Journal Article
Language:English
Published: England Elsevier Ltd 22.06.2024
Elsevier Limited
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
United States > US
ISSN:0140-6736, 1474-547X, 1474-547X
Online Access:Get full text
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Description
Summary: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<0·0001). Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; the only grade 3 or 4 TEAE that occurred in more than 5% of patients receiving vimseltinib was increased blood creatine phosphokinase (eight [10%] of 83). One patient in the vimseltinib group had a treatment-related serious TEAE of subcutaneous abscess. No evidence of cholestatic hepatotoxicity or drug-induced liver injury was noted. Vimseltinib produced a significant objective response rate and clinically meaningful functional and symptomatic improvement in patients with TGCT, providing an effective treatment option for these patients. Deciphera Pharmaceuticals.
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Hans Gelderblom and William D. Tap contributed equally to this publication.
All authors had access to the data, participated in drafting and reviewing the manuscript, and approved the final version for submission. HG, BH, MGS, RRS, MLS, and WDT participated in the conception and design of the study, along with the sponsor. HG, VB, SS, SB, AJW, MS, NB, ALP, AAR, AI, MA, ALC, GT, KB, JM-B, EP, ST, SP, BCP, PR, ACH, PR, J-YB, and WDT, along with the sponsor, participated in data collection. CT oversaw the statistical analyses. CT, HG, and WDT directly accessed and verified the data reported in this manuscript. Authors employed by Deciphera Pharmaceuticals, LLC contributed to the design and conception of the study, analyzed and interpreted the data in collaboration with all authors, participated in drafting and reviewing the manuscript, and approved the final version for submission. All authors are accountable for all aspects of the work and had final responsibility for the decision to submit for publication.
Contributors
ISSN:0140-6736
1474-547X
1474-547X
DOI:10.1016/S0140-6736(24)00885-7