A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy

Marek Trnĕný, Gregor Verhoef, Martin Js Dyer, Dina Ben Yehuda, Caterina Patti, Miguel Canales, Andrés Lopez, Farrukh T Awan, Paul G Montgomery, Andrea Janikova, Anna M Barbui, Kazimierz Sulek, Maria J Terol, John Radford, Anna Guidetti, Massimo Di Nicola, Laure Siraudin, Laurence Hatteville, Sandrine Schwab, Corina Oprea, Alessandro M Gianni, Marek Trnĕný, Gregor Verhoef, Martin Js Dyer, Dina Ben Yehuda, Caterina Patti, Miguel Canales, Andrés Lopez, Farrukh T Awan, Paul G Montgomery, Andrea Janikova, Anna M Barbui, Kazimierz Sulek, Maria J Terol, John Radford, Anna Guidetti, Massimo Di Nicola, Laure Siraudin, Laurence Hatteville, Sandrine Schwab, Corina Oprea, Alessandro M Gianni

Abstract

This phase II, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab-containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥1 lesion >5 cm) at trial entry. Patients received coltuximab ravtansine (55 mg/m2) in 4 weekly and 4 biweekly administrations until disease progression or unacceptable toxicity. Forty-one patients were eligible for inclusion in the per protocol population. Overall response rate (International Working Group criteria) in the per protocol population, the primary end point, was 18/41 [43.9%; 90% confidence interval (CI:) 30.6-57.9%]. Median duration of response, progression-free survival, and overall survival (all treated patients) were 4.7 (range 0.0-8.8) months, 4.4 (90%CI: 3.02-5.78) months, and 9.2 (90%CI: 6.57-12.09) months, respectively. Common non-hematologic adverse events included asthenia/fatigue (30%), nausea (23%), and diarrhea (20%). Grade 3-4 adverse events were reported in 23 patients (38%), the most frequent being hepatotoxicity (3%) and abdominal pain (3%). Eye disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887).

Trial registration: ClinicalTrials.gov NCT01472887.

Copyright© 2018 Ferrata Storti Foundation.

Figures

Figure 1.
Figure 1.
Inclusion of patients in the per protocol (PP) efficacy analysis. Patients were recruited at 28 sites in the USA, Belgium, Czech Republic, Israel, Italy, Poland, Spain, Turkey, and UK. The PP population consisted of all treated patients who had an evaluable response assessment during or at the end of the treatment protocol or who died due to progressive disease before response assessment, without any important protocol deviations affecting efficacy at study entry. CT: computed tomography; DLBCL: diffuse large B-cell lymphoma. *Some patients met multiple exclusion criteria. †Fourteen patients had primary refractory disease as their only protocol deviation.
Figure 2.
Figure 2.
Duration of response for individual patients in the per protocol population. Patients with a duration of response of 0.03 months were censored to the first documentation of the response, in the absence of another evaluable assessment before the cut-off date. CR: complete response; DLBCL: diffuse large B-cell lymphoma; PR: partial response.
Figure 3.
Figure 3.
Kaplan–Meier curve of progression-free survival (PFS) (per protocol population) and overall survival (OS) (safety population).

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