With its tolerable safety profile and precise mechanism of action, vimseltinib (Romvimza) serves as an effective and valuable addition to the systemic therapy armamentarium for patients with diffuse and symptomatic tenosynovial giant cell tumor (TGCT), according to R. Lor Randall, MD, FACS.

On February 14, 2025, the FDA approved vimseltinib for the treatment of patients with symptomatic TGCT for whom surgical resection may cause severe morbidity or worsening functional limitation.1 This regulatory decision was backed by data from the phase 3 MOTION trial (NCT05059262). In MOTION, patients in the intent-to-treat population who received vimseltinib (n = 83) achieved an objective response rate (ORR) of 40% (95% CI, 29%-51%) at week 25.2 In comparison, the ORR with placebo (n = 40) was 0% (95% CI, 0%-9%; (difference, 40% [95% CI, 29%-51%]; P < .0001).

Moreover, 95% of patients who received vimseltinib had tumor shrinkage per RECIST criteria. The mean change in active range of motion (ROM) from baseline to week 25 in the affected joint and TGCT-specific Patient-Reported Outcomes Measurement Information System (PROMIS) scores were both significantly higher with vimseltinib vs placebo.

“[Vimseltinib] is another effective agent for the multidisciplinary team to use in treating patients with diffuse TGCT,” Randall said in an interview with OncLive®. “There is proven efficacy, and the tolerability is terrific; [rates of] transaminitis and [other] liver problems are diminished with this new drug.”

In the interview, Randall discussed the significance of this approval, highlighting the importance of developing alternatives to surgery for patients with diffuse TGCT, who are at high risk of relapse following surgery. He also emphasized the importance of collaboration between orthopedic surgeons and medical oncologists to individualize and optimize treatment approaches for patients with this disease.

Randall is the David Linn Endowed Chair for Orthopaedic Surgery, as well as the chair of and a professor in the Department of Orthopaedic Surgery at the University of California Davis Comprehensive Cancer Center in Sacramento.

OncLive: How does this approval address unmet needs for patients with symptomatic TGCT?

Randall: I’m grateful to speak about this important addition to the armamentarium for patients with TGCT. [The FDA approval of vimseltinib] increases the [treatment] options available to providers and patients. Surgery remains the backbone of [treatment for] most cases [of TGCT]. For clarity, there is the nodular, or limited, variant [of TGCT] and the diffuse type. In this discussion, we’re going to be talking mostly about the diffuse type.

For the limited type [of TGCT], surgery is the mainstay and [is associated with] overall high efficacy and minimal local recurrence. The real problem for patients and providers is diffuse-type [TGCT]. Historically, these [cases] have high local recurrence rates when treated with surgery. Generally, [diffuse-type TGCT is located] around the knee. Orthopedic surgeons and orthopedic oncologists [will access the tumors] either arthroscopically or [with open surgical approaches] and perform major surgery, unfortunately just for many of these tumors to grow right back. 

A variety of TKIs have come [into the sarcoma treatment arsenal] over the years that haven’t been specifically indicated for use in TGCT. [In 2019], the FDA approved the drug pexidartinib [Turalio], which is a CSF1R inhibitor, [for the treatment of adult patients with TGCT that is associated with severe morbidity or functional limitations and is not responsive to surgery]. That is a great addition to the armamentarium. It’s the first approved drug that has helped patients when surgery isn’t indicated or has proven not to be effective.

Now there’s another [drug in this setting with the FDA approval of vimseltinib]. It is a different option from pexidartinib, but both are great drugs. One is not necessarily better than the other. They both have indications [for this patient population]. Many patients have been effectively treated with pexidartinib and achieved good local control. However, [vimseltinib’s] switch pocket [inhibition] specificity [for] CSF1R makes this drug very specific.

What were the key efficacy, safety, and QOL findings from the MOTION trial?

The efficacy [of vimseltinib] was apparent [compared with] placebo. [MOTION had] a 2:1 randomization. For every 3 patients, on average, 2 received vimseltinib, and 1 received placebo. The MOTION trial demonstrated that the ORR with [vimseltinib] was 40% compared with 0% with placebo. The PROMIS scores were significantly improved [with vimseltinib vs placebo]. The ROM and the total volume shrinkage were improved in the [vimseltinib] group vs the [placebo group].

All these [outcomes] speak to the fact that [vimseltinib] is a great new drug. It had good tolerability. The transaminitis and other significant adverse effects [AEs] to the liver were minimal, and the drug had a good AE profile with few grade 3 or 4 toxicities.

What disease factors and patient characteristics might influence the choice between vimseltinib, pexidartinib, and surgery for individual patients?

[Pexidartinib has offered] real advantages for treating patients. If patients are well treated with pexidartinib, they should not switch [to vimseltinib]. If pexidartinib isn’t working out, or the patients need to try something else, vimseltinib is a new option with good efficacy and safety profiles that are exciting. However, for patients who are receiving pexidartinib and doing well, there should be no reason to switch over to this new agent.

This [approval] is exciting [and will require] medical oncologists to partner [with other specialties in[ the [sarcoma] space. [Oncologists treating] patients with TGCT need to make informed decisions with their orthopedic surgery colleagues. [The TGCT field] needs to have a tumor board or consensus around when to treat and when not to treat.

[The issues that arise with TGCT are typically] QOL issues, and any drug can be associated with AEs. When [the aim of the drug is to improve] QOL [and the length of that] life itself [is not] on the line, we need to be careful and use discretion [when determining] whether we use surgery, do observation, or choose drug A or B. All [these strategies] have potential risks, so [everyone] needs to be well informed, and a good consensus between surgeons and medical oncologists [needs to be present] in decision-making.

References

1. FDA approves vimseltinib for symptomatic tenosynovial giant cell tumor. FDA. February 14, 2025. Accessed March 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vimseltinib-symptomatic-tenosynovial-giant-cell-tumor
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