Phase III ENLIVEN study and extension study of CSF 1R shows response in tenosynovial giant cell tumor.

Daiichi Sankyo announced that new data from a pooled analysis of the phase III ENLIVEN study and phase I extension study showed continued treatment with CSF 1R (pexidartinib) resulted in an increased tumor response rate in tenosynovial giant cell tumor (TGCT) patients. The long-term pooled results showed the best overall response with pexidartinib at a median treatment duration of 17 months was 54 percent by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and 64 percent by Tumor Volume Score (TVS). The median duration of response was not reached. The safety profile of pexidartinib in the long-term follow-up was consistent with what has been seen in previous analyses. Across the studies, the most frequent adverse events were hair color change (75%), fatigue (60%), nausea (45%), arthralgia (38%), aspartate aminotransferase (AST) increase (30%) and diarrhea (30%).

Pexidartinib was associated with two clinically distinct types of hepatic adverse reactions. The first was frequent dose-dependent aminotransferase elevations that may be a pharmacologic effect of CSF 1R inhibition. The second hepatic adverse reaction was an idiosyncratic serious mixed or cholestatic hepatotoxicity. Across the pexidartinib clinical program, there were two irreversible cases of cholestatic liver injury, both in non-TGCT study populations. One patient died with advanced cancer and ongoing liver toxicity and one patient required a liver transplant. The data will be presented during a Poster Session on Saturday, June 1, at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

Comment: Recurrence rates for localized TGCT are estimated to be up to 15 percent following complete resection. Diffuse TGCT recurrence rates are estimated to be about 20 to 50 percent following complete resection. TGCT affects all age groups; the diffuse type, on average, occurs most often in people below the age of 40, and the localized type typically occurs in people between 30 and 50 years old.