Phase I/II study of brentuximab vedotin in pediatric patients (pts) with relapsed or refractory (RR) Hodgkin lymphoma (HL) or systemic anaplastic large-cell lymphoma (sALCL): Interim phase (ph) I safety data.

Abstract

10028 Background: Brentuximab vedotin (ADCETRIS) is a novel antibody-drug conjugate that targets CD30, a cell surface antigen expressed by HL and sALCL. The ph 1 portion of this study evaluated safety, pharmacokinetics (PK), and recommended ph 2 dose (RP2D) of brentuximab vedotin in pediatric pts with RR CD30-expressing tumors. Methods: Ph 1/2, open-label, multicenter study in pts aged 2 to <18 years with RR HL or sALCL (5 to <18 years for HL). Pts received brentuximab vedotin by IV infusion once every 21 days (Q3wk). Ph 1 start dose was 1.4 mg/kg escalated to 1.8 mg/kg in a traditional 3+3 design. Results: 12 pts (median age 14.5 y; 10 HL; 2 sALCL) received brentuximab vedotin in the ph 1 portion (mg/kg/dose [n]: 1.4, [3]; 1.8 [9]). 1.8 mg/kg cohort was expanded from 6 to 9 pts to raise the ph 1 pediatric experience to 12 pts before the ph 2 portion. At data cut, pts had received a median of 3 cycles (range, 1–8). 11 pts (92%) had ≥1 treatment-emergent adverse event (TEAE): 2 at 1.4 mg/kg, 9 at 1.8 mg/kg. 6 pts (50%) had Gr ≥3 TEAE: 1 at 1.4 mg/kg, 5 at 1.8 mg/kg. The most frequent (≥15%) TEAE were nausea (50%), abdominal pain, diarrhea (25% each), upper abdominal pain, cough, fatigue, hypokalemia, leukopenia, decreased lymphocyte count, pain, paresthesia, vomiting, weight loss (17% each). 1 pt (8%) discontinued due to TEAE (Gr 3 hepatotoxicity). 7 serious AE (SAE) were reported in 4 pts at 1.8 mg/kg: Gr 2 supraventricular tachycardia unrelated to treatment in 1 pt; Gr 3 febrile neutropenia, Gr 3 hepatotoxicity and Gr 3 cardiac failure (not a cardiac event per later analysis) in 1 pt; Gr 3 bronchospasm and Gr 2 laryngeal edema in 1 pt; 1 cardiac arrest resulting in death, unrelated to treatment. 2 dose limiting toxicities were reported in 1 pt in the 1.8 mg/kg cohort (SAE: prolonged Gr 3 liver event, Gr 3 febrile neutropenia). PK data will be presented. Conclusions: Brentuximab vedotin is generally well tolerated in pediatric pts with RR CD30-positive HL or sALCL up to 1.8 mg/kg Q3wk. For the majority of pts, toxicities were generally mild to moderate and did not lead to discontinuation. 1.8 mg/kg is the RP2D for pediatric and adult pts. The ph 2 portion is ongoing. Clinical trial information: NCT01492088.