Pexidartinib Shows Long-Term Safety and Efficacy in Symptomatic TGCT

Tenosynovial Giant Cell Tumor |
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Treatment with pexidartinib (Turalio) produced sustain clinical benefit among patients with symptomatic tenosynovial giant cell tumor (TGCT) who were not amenable to improvement with surgery, according to final long-term findings from the open-label extension of the phase 3 ENLIVEN trial (NCT02371369).1

Data published in The Oncologist demonstrated that at a median follow-up of 31.2 months (range, 2-66), patients who received pexidartinib (n = 91) achieved an overall response rate (ORR) of 60% (95% CI, 50%-70%) per RECIST 1.1 criteria.2 The median duration of response (DOR) was not reached (NR; 95% CI, 0.03+ to 63.4+ months). The ORR and DOR by tumor volume score (TVS) were 68% (95% CI, 58%-77%) and NR (95% CI, 0.03+ to 63.5+ months).

In August 2019, the FDA approved pexidartinib for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations that was not likely to improve with surgery.3 This regulatory decision was supported by prior data from ENLIVEN.

“Prior to the approval of pexidartinib, the first FDA-approved systemic therapy for TGCT, there were limited treatment options beyond additional surgery,” Andrew Wagner, MD, PhD, medical director of Ambulatory Oncology and a senior physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, in Boston, Massachusetts, stated in a news release.1 “The final results of the ENLIVEN trial show the potential for long-term tumor responses with pexidartinib treatment with a safety profile consistent with earlier findings.”

ENLIVEN was a placebo-controlled study that enrolled patients with histologically confirmed, advanced, symptomatic TGCT with measurable tumors of at least 2 cm per RECIST 1.1 criteria for whom surgical resection was associated with a potential for worsening of functional limitation or severe morbidity.2 The primary analysis (part 1) of the trial examined the efficacy and safety of pexidartinib up to the end of the double-blind portion at week 25. In part 2, patients received open-label continuation of pexidartinib or were permitted to cross over to the pexidartinib arm from the placebo arm.

During part 1, patients received pexidartinib at 1000 mg or matching placebo via a 400-mg delivery in the morning and a 600-mg delivery in the evening for 2 weeks; this was followed by 400 mg twice daily for 22 weeks. Patients treated in part 2 crossed over from the placebo arm to receive pexidartinib at 800 mg split twice daily or the continued dose of the agent that they received at the end of part 1. Treatment continued until disease progression, unacceptable toxicity, or trial completion.

The primary end point was ORR per RECIST 1.1 criteria. Secondary end points included mean change from baseline in range of motion of the affected joint, ORR per TVS criteria, mean change from baseline in the Patient-Reported Outcomes Measurement Information System−Physical Function scale, mean change from baseline in worst stiffness numeric rating scale (NRS), mean change from baseline in Brief Pain Inventory worst pain NRS, and DOR per RECIST 1.1 and TVS criteria.

Additional findings from ENLIVEN showed that patients who were randomly assigned to receive pexidartinib in parts 1 and 2 (n = 61) achieved an ORR of 61% (95% CI, 48%-72%) per RECIST 1.1 criteria. The median DOR was NR (95% CI, 4.6+ to 63.4+ months). The ORR and median DOR per RECIST 1.1 criteria among patients who crossed over to pexidartinib in part 2 (n = 30) were 60% (95% CI, 42%-75%) and NR (95% CI, 0.03+ to 56.0+ months), respectively.

Safety findings revealed that the toxicity profile of pexidartinib in part 2 was consistent with what was reported in part 1. In part 2, 97% of patients experienced treatment-emergent adverse effects (TEAEs) related to pexidartinib and 44% of patients had grade 3 or higher TEAEs. Common grade 3 or 4 TEAEs included increased alanine aminotransferase levels (10%), increased aspartate aminotransferase levels (9%), and hypertension (8%).

“The final results of ENLIVEN contribute to the body of evidence supporting the long-term benefit of pexidartinib,” Patricia Judson, MD, vice president of US Medical Affairs at Daiichi Sankyo, added in the news release.1 “Daiichi Sankyo is proud to have led the discovery and development of the first FDA-approved oral medicine for this rare disease. Since its approval nearly 6 years ago, more than 750 patients in the US have been treated with pexidartinib and we remain committed to working closely with health care professionals to help identify appropriate patients who may benefit from this treatment.”

References

1. Turalio® final long-term data showed sustained clinical benefit in patients with tenosynovial giant cell tumor from open-label extension of ENLIVEN phase 3 trial. News release. Daiichi-Sankyo. July 9, 2025. Accessed July 9, 2025. https://www.businesswire.com/news/home/20250709712562/en/TURALIO-Final-Long-Term-Data-Showed-Sustained-Clinical-Benefit-in-Patients-with-Tenosynovial-Giant-Cell-Tumor-from-Open-Label-Extension-of-ENLIVEN-Phase-3-Trial
2. 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):oyae345. doi:10.1093/oncolo/oyae345
3. FDA approves pexidartinib for tenosynovial giant cell tumor. FDA. Updated August 8, 2019. Accessed July 9, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pexidartinib-tenosynovial-giant-cell-tumor