Final ENLIVEN Trial Results Confirm Long-Term Benefit of Turalio in Tenosynovial Giant Cell Tumor

Daiichi Sankyo has shared final long-term data from the Phase III ENLIVEN clinical trial (NCT02371369). In the study, treatment with Turalio (pexidartinib) showed a sustained clinical benefit in patients with symptomatic tenosynovial giant cell tumor (TGCT) not amenable to improvement with surgery.¹

In a press release, Andrew Wagner, MD, PhD, medical oncologist, Dana-Farber Cancer Institute and Harvard Medical School, said: “Prior to the approval of Turalio, the first FDA-approved systemic therapy for TGCT, there were limited treatment options beyond additional surgery. The final results of the ENLIVEN trial show the potential for long-term tumor responses with Turalio treatment with a safety profile consistent with earlier findings.”

Turalio demonstrates sustained responses in long-term ENLIVEN data

Final long-term results from the second part of the ENLIVEN study showed:

• In patients with advanced, symptomatic TGCT not eligible for surgery (n=91), the overall response rate (ORR) was 60% by RECIST and 68% by TVS, based on long-term follow-up.
• The median follow-up duration was 31.2 months (range: 2–66 months).
• Among responders, the median duration of response had not yet been reached, with extended follow-up of up to 50 months.
• A total of 91 patients received Turalio in this phase of the study, as of the April 30, 2021 data cut-off.

Safety profile remains consistent over extended treatment duration

Additionally, the safety profile of Turalio was consistent with previous findings from the first part of ENLIVEN, with no new safety signals identified.

• The most frequent grade ≥3 treatment emergent adverse events (TEAEs) were elevated alanine aminotransferase (ALT) at 10%, elevated aspartate aminotransferase (AST) at 9%, and high blood pressure at 8%.
• About 31% of patients experienced AST or ALT levels at least three times the upper limit of normal, and 19% had increases of five times or more.
• Serious TEAEs occurred in 23.1% of participants treated with Turalio.

In the press release, Patricia Judson, MD, vice president, US medical affairs, Daiichi Sankyo, added: “The final results of ENLIVEN contribute to the body of evidence supporting the long-term benefit of Turalio. 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 six years ago, more than 750 patients in the US have been treated with Turalio and we remain committed to working closely with healthcare professionals to help identify appropriate patients who may benefit from this treatment.”

Initial FDA approval supported by early ENLIVEN data

Turalio was approved by the FDA in August 2019 for adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. The approval was based on durable ORR observed earlier in ENLIVEN.²

At the time of the approval, positive results from the trial showed:

• After 25 weeks, the overall response rate was 38%, including 15% complete responses and 23% partial responses.
• No responses were observed in the placebo group (p<0.0001).
• Among those followed for at least six months post-response, 22 out of 23 maintained their response for six months or longer.
• All 13 patients followed for at least 12 months post-response sustained their response for a year or more.

Trial design included crossover and long-term follow-up

ENLIVEN is a global, double-blind, randomized, placebo-controlled study. In the first part, 120 patients were randomized to receive either Turalio at 1,000 mg daily for two weeks followed by 800 mg daily for 22 weeks or matching placebo.

Following completion of the first part of the trial, patients were offered to enter a long-term, open-label portion. In this second part of the study, 91 patients either crossed over from placebo to receive Turalio at 800 mg twice daily (without loading dose) or continued the dose of Turalio received at the end of the first part of the trial until tumor progression, toxicity, or study completion.

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. FDA approves pexidartinib for tenosynovial giant cell tumor. FDA. Accessed July 9, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pexidartinib-tenosynovial-giant-cell-tumor