A phase I study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma
Mené sur 28 patients atteints d'un lymphome hodgkinien réfractaire ou récidivant, cet essai de phase I évalue la dose maximale tolérée, la toxicité et l'activité antitumorale d'un anticorps bispécifique anti-CD30/CD16A
The bispecific, tetravalent antibody AFM13 represents a new approach engaging natural killer cells via CD16A to fight CD30+ malignancies.AFM13 is well tolerated and active in Hodgkin lymphoma patients who received all standard therapies including brentuximab vedotin. AFM13 is a bispecific, tetravalent chimeric antibody construct (TandA®) designed for the treatment of CD30-expressing malignancies. AFM13 recruits natural killer (NK) cells via binding to CD16A as immune effector cells. In this phase I dose escalation study 28 patients with heavily pre-treated relapsed or refractory Hodgkin lymphoma received AFM13 at doses of 0.01 to 7mg/kg body weight. Primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics (PK), anti-tumor activity and pharmacodynamics (PD). Adverse events were generally mild to moderate. The maximum tolerated dose was not reached. PK assessment revealed a half-life of up to 19 hours. Three of 26 evaluable patients achieved partial remission (11.5%) and 13 patients achieved stable disease (50%) with an overall disease control rate of 61.5%. AFM13 was also active in brentuximab vedotin refractory patients. In 13 patients who received doses of ≥1.5mg/kg AFM13 the overall response rate was 23% and the disease control rate was 77%. AFM13 treatment resulted in a significant NK-cell activation and decrease of soluble CD30 in peripheral blood. In conclusion, AFM13 represents a well-tolerated, safe and active targeted immunotherapy of Hodgkin lymphoma. A phase II study is currently planned to optimize the dosing schedule in order to further improve the therapeutic efficacy. The phase I study is registered to www.clinicaltrials.gov as NCT01221571.
Blood 2015