DLBCL

Coltuximab ravtansine (SAR3419) phase II trial shows moderate clinical activity in R/R DLBCL patients

A phase II study investigated the use of coltuximab ravtansine (SAR3419) in patients with relapsed refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The study was published in Haematologica by Marek Trněný, Head of the 1st Department of Internal Medicine at Charles University, Prague, and colleagues on 10 May 2018.

The study was single-arm and multi-center assessing the safety and efficacy of SAR3419 in patients who had been previously treated with rituximab-containing immunochemotherapy. SAR3419 is an anti-CD29 antibody-drug conjugated to DMR, a cytotoxic maytansinoid. It has shown clinical benefit in previous phase I studies and a maximum tolerated dose (MTD) was identified as 55 mg/m2.

Study Overview
  • N = 61 patients (median age = 69 years; range, 30–88) were included in the study and received four weekly doses of SAR3419 (55 mg/m2) intravenously, then bi-weekly doses after a rest period until disease progression (PD) or unacceptable toxicity
  • Patients had a confirmed diagnosis of R/R CD19-positive DLBCL and were enrolled between Jan 2012 – July 2013
  • The patients had a median of 2 prior treatment regimens (range, 0–9), and they received a median of 3 cycles of study treatment (range, 1–10) and had a median duration of treatment of 13.3 weeks (range, 5–41)
  • The primary endpoint was overall response rate (ORR). Secondary endpoints included; duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety
Key Findings
  • In the per-protocol population (n = 41) the ORR was 43.9% (90% CI, 30.6–57.9%)
    • Complete response (n = 6)
    • Partial response (n = 12)
  • Median DOR: 4.7 months (0.0–8.8)
  • Median PFS: 4.4 months (90% CI, 3.02–5.78)
  • Median OS: 9.2 months (90% CI, 6.57–12.09)
  • At the time of analysis 6 May 2014, n = 5 patients still on therapy and n = 6 with relapsed disease still were having a response to treatment
Safety
  • Adverse events (AEs) grade ≥3 occurred in n = 31 patients, most common AEs included; neutropenia (n = 15), lymphopenia (n = 13) and leukopenia (n = 9)
  • N = 15 patients were reported to have experienced eye disorders but none required dose modification as a result. Ocular toxicity was observed in a previous trial in which the MTD was 160 mg/m2
  • PD was the main reason for discontinuation (n = 47), AEs (n = 6) or investigator’s decision (n = 3)

The authors concluded that SAR3419 demonstrated a moderate clinical response in R/R DLBCL patients with an acceptable toxicity profile. They also observed that the response rates were lower in patients who were refractory to previous treatment. A further study with a higher number of patients could be beneficial to conduct further analysis.

References
  1. Trněný M. Et al. A phase 2 multicenter study of the anti-CD19 antibody drug conjugate coltixumab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. Haematologica. 2018 May 10. pii: haematol.2017.168401. doi: 10.3324/haematol.2017.168401. [Epub ahead of print]
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