Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
Mené sur 92 patients atteints d'un lymphome non hogkinien réfractaire ou récidivant, cet essai de phase IIa évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un composé appelé MOR208, un anticorps anti-CD19, en fonction du sous-type de la maladie (lymphome diffus à grandes cellules B, lymphome folliculaire, lymphome à cellules du manteau, autre lymphome non hodgkien indolent)
Background : This two-stage, phase IIa study (ClinicalTrials.gov: NCT01685008) investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin’s lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in B-cell malignancies, but not by hematological stem cells. Patients and methods : Patients aged ≥18 years, with R-R NHL progressing after ≥1 prior rituximab containing regimen were enrolled into subtype-specific cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8 weeks. Patients with at least stable disease could continue treatment for an additional 4 weeks. Those with a partial or complete response after 12 weeks could receive extended MOR208 treatment (12 mg/kg, either monthly or every second week) until progression. The primary endpoint was overall response rate. Results : Ninety-two patients were enrolled: DLBCL (n=35), FL (n=34), other iNHL (n=11) and MCL (n=12). Responses were observed in DLBCL, FL and other iNHL cohorts (26%, 29% and 27%, respectively). They lasted ≥12 months in 5/9 responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in nine patients are ongoing (>26 months in five instances). Patients with rituximab refractory disease showed a similar response rate and progression-free survival time to patients with non-refractory disease. The most common adverse events (any grade) were infusion-related reactions (IRRs; 12%) and neutropenia (12%). One patient experienced a grade 4 IRR and eight patients (9%) grade 3/4 neutropenia. No treatment-related deaths were reported. Conclusions : MOR208 monotherapy demonstrated promising clinical activity in patients with R-R DLBCL and R-R FL, including in patients with rituximab refractory tumors. These efficacy data and the favorable safety profile support further investigation of MOR208 in phase II/III combination therapy trials in R-R DLBCL.ClinicalTrials.gov numberNCT01685008
Annals of Oncology 2018