Vimseltinib Shows Efficacy in Rare Tenosynovial Giant Cell Tumors

Promising efficacy and safety data seen with vimseltinib in the treatment of patients with tenosynovial giant cell tumor (TGCT) notably also showed improvements in quality of life (QOL), according to R. Lor Randall, MD, FACS.

“These are very encouraging preliminary results of a randomized, placebo-controlled trial looking at vimseltinib in a benign but locally aggressive condition that medical oncologists will be involved in treating. The company is taking [the agent] forward to the FDA for approval,” Randall said in an interview with OncLive^®.

The FDA granted priority review to the new drug application for the oral switch-control TKI vimseltinib for the treatment of patients with TGCT in August 2024. The target action date for the decision is February 17, 2025.¹ Data from the pivotal phase 3 MOTION trial (NCT05059262) revealed thatthe objective response rate (ORR) was 40% among patients who received vimseltinib (n = 83) compared with 0% for those given placebo (n = 40; difference, 40%; 95% CI, 29%-51%; P < .0001).²

In the interview, Randall highlighted key findings from MOTION. In a concurrent interview, he detailed how he approaches the treatment of patients with TGCT and the potential of vimseltinib to join pexidartinib in the field. Randall is the David Linn Endowed Chair for Orthopedic Surgery, the chair of the Department of Orthopedic Surgery, and a professor at the University of California Davis Comprehensive Cancer Center in Sacramento, California.

OncLive: How was the MOTION trial examining vimseltinib in patients with TGCT conducted?

Randall: MOTION was a double-blind, randomized, [placebo]-controlled trial. It was international and there were 35 sites. [The design] was a 2:1 randomization of the drug vs placebo for a 24-week period and there is a subsequent open-label period. [However], the publication [of the data is solely on] the first 24-week [period of the] trial.

[Data on vimseltinib vs placebo] showed a real improvement in the primary and secondary end points. The primary end point was ORR based upon RECIST 1.1 criteria, but the secondary end points are as important for QOL. There was the ORR per tumor volume score [TVS] and the mean change from baseline [to week 25] in active range of motion, PROMIS [Patient-Reported Outcomes Measurement Information System] scores, stiffness, and in a couple of pain parameters as well. When we talk about this with our patients, it’s those latter points that matter most. Although they’d like their tumor to shrink, more importantly, they want to feel better. Those are [end points] worth emphasizing.

What were the key findings from MOTION?

We were able to enroll a fair number of patients as there were 83 on the treatment arm and 40 on the placebo-controlled arm. The demographics were similar [between arms].

What was exciting to see was that the primary end point of ORR by RECIST criteria was 40% in the vimseltinib arm and 0% in the placebo arm, which is non-equivocal that there’s an effect. In terms of the secondary end points, the ORR by independent radiologic review [per] TVS was 67% for vimseltinib and 0% for placebo. [These] 2 measures of objective response are very impressive. The partial response rate is a surrogate for how the patient is doing. It’s fair to say if the tumor is shrinking, they’re more likely to feel better, but what we really want to know is whether the patients are feeling better. The data are encouraging.

Range of motion [from baseline] to 25 weeks prior to the crossover, the PROMIS scores, stiffness scores, and a couple of pain scores, were all statistically significant for being improved [with vimseltinib vs placebo]. Also, it’s important that all these improvements were seen in the face of a relatively benign adverse effect [AE] profile. Treatment-emergent AEs were mostly grade 1 and grade 2. One point that is very important to emphasize is that the elevated transaminase [levels], alanine aminotransferase particularly, were benign with mild increases. There were no grade 3 or 4 increases [aside from blood creatine phosphokinase levels], which is a concern about some other drugs that are available on the market.

Are these results from such a small trial compelling enough to encourage the use of this agent?

It shows the different paradigms [in terms of trial size]. People who are treating [patients with] very common condition [such as] breast, prostate, lung and non-solid tumor cancers [see larger trials in their field]. TGCT is very rare, like sarcomas [are]. If we bundle it into the sarcoma paradigm, 123 patients for a randomized, placebo-controlled trial that’s double-blinded is massive. It shows you the relative rarity of these conditions. Through the scientific stringency lens, yes, there should be some trepidation here, but from a practical lens this is a rare condition. It took 35 centers from around the world to be able to accrue this [patient population, so the data] are worth a nod.

How does vimseltinib compare with pexidartinib (Turalio)?

[Vimseltinib] is probably not going to need any sort of REMS [Risk Evaluation and Mitigation Strategy] program, [whereas pexidartinib is only available through the Turalio REMS program], because the liver toxicity is much more favorable. [Whether vimseltinib requires a REMS program is] to be determined by others, but this is an agent that can be used with more confidence [because] of its benignity in terms of AEs.

Vimseltinib does have many of the AEs [that] some TKIs do—it [can lead to] edema issues [and] it does bump the transaminase [levels up] a bit, so patients will need to be surveilled. But overall, the surveillance for AEs will be much less onerous, so patients will be less inclined to remove themselves from treatment.

Disclosures: Dr Randall is a consultant for Deciphera Pharmaceuticals, the manufacturer of vimseltinib.

References

1. U.S. Food and Drug Administration accepts for priority review Deciphera’s new drug application for vimseltinib for the treatment of patients with tenosynovial giant cell tumor (TGCT). News release. Ono Pharmaceutical, Ltd. August 16, 2024. Accessed September 3, 2024. https://www.ono-pharma.com/en/news/20240816.html
2. Gelderblom H, Bhadri V, Stacchiotti S, et al. Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;403(10445):2709-2719. doi:10.1016/S0140-6736(24)00885-7