Vimseltinib Shows Statistically Significant Improvement in 25-Week ORR in TGCT
The phase 3 MOTION study met its primary end point of objective response rate at week 25, as well as key secondary end points, when patients with tenosynovial giant cell tumor were given vimseltinib.
Tumor Cell:© nevio - stock.adobe.com
The primary end point of objective response rate (ORR) at week 25 was met at 40% (95% CI, 29%-51%) for patients with tenosynovial giant cell tumor (TGCT) not amenable to surgery treated with vimseltinib (DCC-3014) vs 0% (95% CI, 0%-9%) for patients treated with placebo (P <.0001) in the pivotal, phase 3 MOTION study (NCT05059262).1
According to positive top-line results from the trial based on a data cutoff date of August 22, 2023, all of the key secondary end points were also met with statistically significant and clinically meaningful improvements observed in patients treated with vimseltinib at week 25 vs those given placebo. This includes an ORR by tumor volume score (TVS) of 67% in the vimseltinib treated group vs 0% in the placebo treated group (P < .0001).
The ORR at week 25 in the intention-to-treat (ITT) population based on blinded independent radiologic review (IRR) per TVS was 67% (95% CI, 56%-77%) for patients in the vimseltinib arm vs 0% (95% CI, 0%-9%) among those in the placebo arm (P <.0001). An improvement in mean change from baseline in active range of motion at week 25 was also observed with vimseltinib (18.4%) vs placebo (3.8%; P =.0077).
For safety, vimseltinib was well-tolerated and no evidence of cholestatic hepatotoxicity was observed in patients treated with vimseltinib. In the vimseltinib arm, 6% of patients with treatment-emergent adverse events (TEAEs) discontinued treatment. The most common any grade TEAEs >15% seen in the vimseltinib vs placebo arm included periorbital edema (45% v 13%), fatigue (33% v 15%), face edema (31% v 8%), pruritus (29% v 8%), and headache (28% v 26%). In the vimseltinib group, the most common grade 3/4 TEAEs were creatine phosphokinase increased (10%), hypertension (5%), periorbital edema (4%), pruritus (2%), and face edema, headache, asthenia, and maculopapular rash in 1% each.
“Patients suffering from TGCT are in need of a new treatment option that offers both strong clinical benefit and a well-tolerated safety profile,” said Hans Gelderblom, MD, PhD, chair of the Department of Medical Oncology at Leiden University Medical Center, in a press release. “TGCT has a significant negative impact on the daily life of patients who face substantial pain, stiffness, and impaired mobility. Success across both the primary and all key secondary endpoints in MOTION underscores vimseltinib’s ability to help TGCT patients feel and function better. The top-line results from MOTION, together with the impressive data announced today from the phase 1/2 study showing that the response rates with vimseltinib continue to increase over time, and that patients continue to receive long-term clinical benefit as evidenced by the median duration of treatment, demonstrates vimseltinib’s potential to become a best-in-class agent.”
Vimseltinib is an investigational, orally administered, potent, and highly selective switch-control kinase inhibitor of CSF1R.
MOTION, a 2-part, randomized, double-blind, placebo-controlled, phase 3 study, is evaluating the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy. Patients who have received prior therapy with imatinib (Gleevec) or nilotinib (Tasigna) are not eligible for enrollment.
Patients were eligible for enrollment if they had symptomatic disease defined as at least moderate stiffness or at least moderate pain, receipt of a stable analgesic regimen for at least 2 weeks prior to the first dose of the treatment with the study drug, measurable disease per RECIST v1.1 criteria with at least 1 measurable lesion of at least 2 cm, and adequate organ and bone marrow function.2
In part 1 of the study, 123 patients were randomized in a 2:1 fashion to receive either 30 mg twice weekly of vimseltinib (n = 83) or placebo (n = 40) for 24 weeks. In the phase 2, open-label portion of MOTION, patients from the vimseltinib arm, as well as the placebo arm, are being treated with vimseltinib. Investigation of this portion of the trial remains ongoing.1
In addition to MOTION, updated results from a phase 1/2, open-label, multicenter study (NCT03069469) of vimseltinib for the treatment of 97 patients with TGCT were reported from the June 27, 2023, cutoff date. In phase 1, 32 patients were enrolled in 3 cohorts across multiple doses and in phase 2, 65 patients were enrolled in 2 cohorts at the recommended phase 2 dose of 30 mg twice a week.3 Cohort A included 46 patients with TGCT with no prior anti-CSF1/CSF1R therapy, and cohort B included 19 patients with prior anti-CSF1/CSF1R therapy.1
With a median treatment duration of 25.1 months for phase 1 of the study and 21.0 months in cohort A of phase 2, treatment with vimseltinib demonstrated a best ORR of 72% and 64%. In addition, updated data from cohorts A and B from phase 2 showed that clinically meaningful symptomatic benefits were seen at week 25 across multiple secondary efficacy end points, including best ORR per TVS in cohort A, and active range of motion, physical function, stiffness, and pain.
For safety, vimseltinib was well-tolerated in patients with TGCT and consistent with what has been previously observed with the agent. No evidence of cholestatic hepatotoxicity was seen and 9% of patients discontinued treatment due to TEAEs.
Further data from this phase 1/2 study will be presented at the Connective Tissue Oncology Society 2023 Annual Meeting in Dublin, Ireland, on November 1-4, 2023. A new drug application to the FDA for vimseltinib for the treatment of patients with TGCT is expected in the second quarter of 2024, and a marketing authorization application to the European Medicines Agency is expected in the third quarter of 2024.
REFERENCES:
Deciphera Pharmaceuticals announces positive top-line results from motion pivotal phase 3 study of vimseltinib in patients with tenosynovial giant cell tumor (TGCT) and updated results from phase 1/2 study of vimseltinib in TGCT. News release. Deciphera Pharmaceuticals, Inc. October 30, 2023. Accessed October 31, 2023. https://tinyurl.com/2dpedb4p
Study of vimseltinib for tenosynovial giant cell tumor (MOTION). ClinicalTrials.gov. Updated March 16, 2023. Accessed October 31, 2023. https://clinicaltrials.gov/study/NCT05059262
Study of DCC-3014 in patients with advanced tumors and tenosynovial giant cell tumor. ClinicalTrials.gov. Updated October 10, 2023. Accessed October 31, 2023. https://clinicaltrials.gov/study/NCT03069469
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