Klin Padiatr 2014; 226 - O_20
DOI: 10.1055/s-0034-1371149

Phase 1/2 Study of Brentuximab Vedotin in Pediatric Pts with Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) or Systemic Anaplastic Large-Cell Lymphoma (sALCL): Preliminary Phase 2 HL Data

F Locatelli 1, K Neville 2, A Rosolen 3, J Landman-Parker 4, N Aladjidi 5, A Beishuizen 6, S Daw 7, L Gore 8, ARK Franklin 9, A Fasanmade 10, J Wang 10, J Sachs 10, C Mauz-Körholz 11
  • 1Bambino Gesù Hospital and University of Pavia, Rome, Italy
  • 2Children's Mercy Hospital, Kansas City, United States
  • 3University of Padua, Padua, Italy
  • 4Hôpital des Enfants Armand-Trousseau, Paris, France
  • 5Hôpital des Enfants, Groupe Hospitalier Pellegrin, Bordeaux, France
  • 6Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands
  • 7University College London Hospitals, London, United Kingdom
  • 8Children's Hospital Colorado, Aurora, United States
  • 9Children's Cancer Hospital at MD Anderson Cancer Center, Houston, United States
  • 10Takeda Pharmaceuticals International Co., Cambridge, United States
  • 11Martin-Luther-University of Halle-Wittenberg Medical Center, Halle, Germany

Question: To evaluate the safety and efficacy of brentuximab vedotin, a CD30-targeted antibody-drug conjugate, in pediatric pts with R/R HL or sALCL (currently approved in the USA and EU for use in adults with R/R HL or sALCL). We report initial phase 2 response, safety and pharmacokinetics (PK) data in R/R HL pts at the RP2D of 1.8 mg/kg Q3wk.

Methods: This ongoing phase 1/2 prospective, open-label, multicenter study is the first brentuximab vedotin clinical trial conducted exclusively in pediatric pts (NCT01492088). The phase 2 primary objective is ORR (CR + PR) at the RP2D; secondary objectives include TTP, TTR, DOR, EFS, PFS, OS, PK, and safety. Pts with R/R HL aged 5 to < 18 y, with measurable disease, at second or later relapse, who had failed chemotherapy and were ineligible for, refused, or previously underwent stem cell transplant, received brentuximab vedotin 1.8 mg/kg Q3wk for up to 16 cycles.

Results: At baseline, the median age of the 16 HL pts was 15 y (range 8 – 18); 56% were male; median time from initial diagnosis was 16.7 mos (range, 0 – 38); 50% had B symptoms. At data cut-off (June 20, 2013), pts had received a median of 3 cycles of treatment (range 1 – 16); 10 (63%) pts had discontinued (progressive disease, n = 7; adverse events [AEs], n = 2; allogeneic transplant, n = 1). For 14 response-evaluable pts, per investigator assessment, the ORR was 64%; 21% pts had CR, and 43% a PR. 12/16 (75%) pts had ≥1 AE; 7 (44%) had Gr ≥3 AEs. The most common (> 3 pts) AEs were nausea (38%), pyrexia (31%), neutropenia, and paresthesia (each 19%). 7 SAEs occurred in 5 pts; 4 SAEs in 3 pts were considered related to study drug: Gr 3 hepatotoxicity and Gr 3 febrile neutropenia (n = 1); Gr 3 anaphylaxis (n = 1); Gr 3 pneumonia (n = 1). 1 pt died of unrelated cardiac arrest; 2 pts discontinued due to Gr 3 hepatotoxicity (n = 1) and Gr 3 peripheral neuropathy (n = 1). Preliminary PK data will be presented.

Conclusions: Brentuximab vedotin 1.8 mg/kg Q3wk (RP2D) was generally well tolerated in pediatric pts with R/R HL. Preliminary evidence of activity showed an ORR to date of 64%, including 21% CR. The phase 2 portion in pediatric pts with R/R HL and sALCL is ongoing.