Phase III ENLIVEN study of CSF 1R shows efficacy and safety in tenosynovial giant cell tumor.- Daiichi Sankyo.

Daiichi Sankyo announced that the phase III ENLIVEN study showed a statistically significant 39 percent overall response rate (ORR) at week 25 based upon central review of MRI scans using Response Evaluation Criteria in Solid Tumors, version 1.1 (the primary endpoint) for patients with tenosynovial giant cell tumor (TGCT) treated with oral CSF 1R (pexidartinib) compared to no tumor response among patients who received placebo. In the ENLIVEN study, hepatic toxicities were more frequent with pexidartinib versus placebo (AST or ALT of at least 3X ULN: 33 percent, total bilirubin of at least 2X ULN: 5 percent, N=61). Eight patients discontinued pexidartinib due to hepatic adverse events (AEs); four were serious nonfatal AEs with increased bilirubin, one lasting ~7 months. In non-TGCT development studies using pexidartinib, two severe liver toxicity cases (one required liver transplant, one was associated with death) were observed. Other AEs noted in ENLIVEN more than 10 percent and more common with pexidartinib included hair color changes, pruritus, rash, vomiting, abdominal pain, constipation, fatigue, dysgeusia, facial edema, peripheral edema, periorbital edema, decreased appetite and hypertension.

Secondary efficacy endpoints demonstrated that patients treated with pexidartinib had a 56 percent overall response rate (ORR) by Tumor Volume Score (TVS), compared to no response in patients who received placebo. Clinically meaningful improvement versus placebo was observed in other secondary efficacy endpoints, including range of motion (+15% vs +6%), PROMIS physical function (+4.1 vs -0.9), and worst stiffness (-2.5 vs -0.3). There was also a nonsignificant improvement in pain response (31% vs 15%). Patients enrolled in the trial were those with tenosynovial giant cell tumor (TGCT) for whom surgery would be associated with potentially worse function or severe morbidity. After a median six month follow-up (longest 17 months), no responders in the ENLIVEN study had progressed. The data will be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.