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 1^st 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.