(P 414) TENOSYNOVIAL GIANT CELL TUMOR IN CHILDREN: INTERIM RESULTS FROM A PHASE 1 STUDY OF TURALIO®

Objective: Tenosynovial Giant Cell Tumor (TGCT) is a rare tumor involving the synovium, bursa or tendon sheath that occur, most commonly, in young and middle-aged adults. However, TGCT can also occur in children and lead to significant pain, swelling and joint stiffness at a critical time of physical growth and activity. Surgery is the current standard practice but can result in significant joint damage, leading to arthritis and lifelong morbidities. Turalio®, an oral selective inhibitor of the receptor tyrosine kinases CSF1R, Kit and Flt3, was approved by the FDA for adult patients with symptomatic TGCT. There is currently no approved systemic therapy for children with TGCT.

Methods: This is a single-arm, open label phase 1 clinical trial of Turalio® for children and young adults with recurrent or refractory solid tumors or leukemia, with a recent focus on TGCT during the expansion cohort. It is dosed daily on a continuous basis for cycles of 28 days. The primary and secondary objectives are to evaluate safety and tolerability of Turalio® in pediatric patients with TGCT and to determine preliminary antitumor activity.

Results: Three of 20 enrolled pediatric patients were treated for TGCT (median age 11 years, range 11-16; 67% female). Their racial and ethnic backgrounds are diverse. Patients had a median of 2 prior surgeries for tumor excision and all had recurrent disease at the time of study enrollment. Two patients had disease in their knee, and one had an affected ankle. At baseline, all experienced daily pain and limited mobility with one patient wheelchair bound. All three patients required reduced activities due to their symptoms and were taking daily non-steroidal anti-inflammatories. During cycle 1, common side effects of Turalio® included fatigue, decreased appetite, dizziness, pruritis, diarrhea, hair lightening and mild elevations in liver function tests, all commonly reported in adult TGCT patients on Turalio®. In the dose escalation cohort of this study, no dose-limiting toxicities were observed. Therefore, patients on the dose expansion were enrolled on the highest dose level, 30 % higher than the FDA approved dose for TGCT in adults. Dose interruptions to minimize drug adverse events occurred in all 3 patients. Turalio was restarted at a low dose with titration up as needed for TGCT-related symptom relief. All three patients remain on study with a median of 16 cycles (1-36). For the 2 patients who have been on study greater than 1 year, both have seen resolution of TGCT-related symptoms and radiographic evidence of response (12% and 62% decrease) while receiving a lower dose than the approved adult dose. Of note, the patient who presented wheelchair bound, has full function of his joint and has resumed all physical activities.

Conclusion: Three pediatric patients with TGCT have been treated with Turalio®. All patients experienced commonly reported side effects that led to dose reduction, however there were no significant adverse events. The first two pediatric patients with TGCT treated on Turalio® saw radiographic response with 62% and 12% decrease in the size of target lesions by RECIST 1.1. More importantly, both had resolution of baseline joint pain and swelling and had full function of their affected joint within 2 cycles. Therefore, in this limited cohort, Turalio appears to be safe and effective in pediatric patients with TGCT.