Pexidartinib Shows Durable Response Among Patients with Tenosynovial Giant Cell Tumors

Final Results From the Phase 3 ENLIVEN Trial

According to the final long-term analysis of the phase 3 ENLIVEN study, pexidartinib demonstrated a sustained clinical benefit among patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. 

As Andrew Wagner, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors stated, “Because TGCT can be a chronic condition, particularly for those with diffuse TGCT not amenable to surgery, it is important to understand the long-term efficacy and safety of pexidartinib in these patients.”

The double-blinded, phase 3 ENLIVEN study enrolled 120 patients with symptomatic, advanced TGCT for whom surgery was not recommended were randomized on a 1-to-1 basis to receive either pexidartinib (n = 61) or placebo (n = 59). In the pexidartinib arm, a loading dose of 1000 mg of pexidartinib was administered daily (400 mg in the morning and 600 mg in the evening) for the first 2 weeks, followed by 800 mg daily (400 mg twice daily) for 22 weeks. Due to emergence of mixed or cholestatic hepatotoxicity, enrollment was terminated early and there was total enrollment of 95% of original target and increased patient withdrawal. The primary end point was overall response rate (ORR) at week 25. As reported previously, the ORR was higher in the pexidartinib arm vs the placebo arm (39% vs 0%; P < .0001).

Following the double-blinded part 1 of the study, there was an open-label continuation of those patients in the pexidartinib arm (n = 48), or who crossed over to pexidartinib treatment from the placebo arm (n = 30; all patients who received ≥1 dose of pexidartinib, n = 78). The primary end point was ORR, with secondary end points including proportion of patients with response based on tumor volume score (TVS).

With a median follow-up duration of 31.2 months, the ORR (by RECIST) was 60%, with no discernible difference between patients who were randomized to pexidartinib initially and those who crossed over in part 2 of the trial (60% vs 61%, respectively). The ORR by TVS was 68%, again with no discernible difference between the 2 cohorts (67% vs 70%). As noted by the study authors, the findings in this analysis are consistent with those results from the primary analysis, while also showing that tumor responses deepen over time. There were no new safety signals identified and no new significant cases of hepatotoxicity.

Dr Wagner et al, concluded, there was a “sustained clinical benefit” with pexidartinib for patients with symptomatic TGCT associated with severe morbidity or functional limitations that was not amenable to improvement with surgery, and there was “increased ORR by RECIST and TVS compared to the end of the blinded phase at week 25.”

Source:

Wagner AJ, Tap WD, Bauer S, et al. Long-term efficacy and safety of pexidartinib in patients with tenosynovial giant cell tumor: Final results of the ENLIVEN study. Oncologist. 2025; 30(7). doi:10/1093/oncolo/oyae345.

Tap WD, Gelderblom H, Palmerini E, et al. Pexidartinib versus placebo for advanced tenosynovial giant cell tumor (ENLIVEN): A randomised phase 3 trial. Lancet. 2019; 394(10197):478-487. doi:10.1016/S0140-6736(19)30764-0.