LAUSR

Introduction: Despite high overall 5‐year survival rates for childhood HL and sALCL, improved options are needed for patients (pts) who do not respond to, or relapse following, initial therapy. This phase 1/ 2 open‐label, dose‐escalation trial (NCT01492088) evaluated the safety, PK, and antitumor activity of the antibody‐drug conjugate, brentuximab vedotin (BV), in pediatric pts with R/R HL or sALCL for whom treatment alternatives do not exist. Methods: BV was administered by intravenous infusion once every 21 days for up to 16 cycles, starting at 1.4 mg/kg up to 1.8 mg/kg to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). BV treatment beyond 16 cycles was permitted for pts with continued benefit. Overall response rate (ORR) was evaluated after 2 cycles and overall survival (OS) was assessed up to 2 years after last pt enrolment. Other secondary endpoints included time to progression/response (TTP/TTR), event/progression‐free survival (EFS/PFS), safety, and PK parameters. Results: Thirty‐six pts age range 7 to <18 years were enrolled and received BV. MTD was not reached. RP2D was determined to be 1.8 mg/kg. Sixteen R/R HL and 17 R/R sALCL pts were treated at the RP2D; 3 R/R HL pts were treated at 1.4 mg/kg. Pts received a median 7 (range 1–20) cycles of BV. Median follow‐up at data‐cut was 19.7 months. ORR (CR + PR) per IRF was 46% with an overall median TTR of 2.7 months. Overall (per IRF) median TTP was 4.8 months; EFS and PFS were 3.0 and 4.8 months, respectively. Median OS was not reached. In pts treated at the RP2D, greater clinical activity was seen in sALCL vs HL: ORR 53 vs 47%, median TTR 1.5 vs 2.7 months, TTP 6.2 vs 4.8 months, PFS 6.2 vs 3.8 months, and EFS 4.8 vs 2.1 months. After BV, 17 pts (47%) proceeded to transplant (including 9 sALCL pts, 6 of whom were first relapse pts). The highest ORR of 60% was seen in first relapse sALCL pts treated at the RP2D. Common treatment‐related adverse events (AEs) included pyrexia (44%), nausea (36%), and paresthesia (19%). The most common grade ≥ 3 AEs (16/36 pts) were neutropenia (11%), increased GGT (6%), and pyrexia (6%). Twelve pts (33%) experienced peripheral neuropathy (PN) of grade 1/2/3 (25%/6%/3%), with 83% resolving/improving by end of treatment; no pt discontinued due to PN. There were 4 treatment‐related serious AEs in 3 pts (all grade 3: hepatotoxicity, febrile neutropenia, pneumonia, and anaphylaxis). One on‐study death was reported but was considered unrelated to study drug per investigator. Conclusions: Response rates were clinically meaningful in this R/R HL and sALCL population with 47% of pts proceeding to transplant. This study shows BV is a feasible treatment option in pediatric HL and sALCL that can facilitate relapsed pts proceeding to transplant. A future study is ongoing to address the efficacy/safety of BV with chemotherapy in pediatric pts with newly diagnosed HL.