ASH 2018 | MOR208 and lenalidomide in R/R DLBCL: Results from the phase II L-MIND trial

On Saturday 1 December 2018, Oral Session 626 took place at the 60^th American Society of Hematology (ASH) Annual Meeting, San Diego, CA. During that session, through Abstract #227 the results from the phase II L-MIND trial were presented by Gilles Salles from South Lyon University Hospital Complex, Lyon, FR.

In this open-label phase II trial (NCT02399085), the efficacy of lenalidomide and MOR208, a humanized, Fc-enhanced, monoclonal anti-CD19 antibody was assessed in relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) patients. MOR208 leads to natural killer (NK)-mediated antibody-dependent cytotoxicity, macrophage-mediated antibody-dependent phagocytosis and direct cell death. MOR208 and lenalidomide combination have shown synergy in various in vitro and in vivo models. The primary endpoint of the study was overall response rate (ORR). Secondary endpoints included, progression-free survival (PFS), overall survival (OS), safety, exploratory biomarker analysis, and duration of response (DoR).

Study design & baseline characteristics

• N = 81 R/R adult patients (< 18 years) with histologically-confirmed DLBCL and:
  • Positron emission tomography (PET)-positive measurable disease (at least one lesion ≥5 x 1.0 cm)
  • One to three prior systemic therapies, including at least one CD20-targeted therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0−2
  • Not eligible for autologous stem cell transplantation
  • Patients with double/triple hit DLBCL or primary refractory DLBCL were excluded
• Dosing (12 cycles of 28 days):
  • MOR208: intravenous administration of 12 mg/kg weekly during cycles 1−3 (plus a loading dose on D4 of cycle 1), and every second week during cycles 4−12
  • Lenalidomide: oral administration of 25 mg per day up to cycle 12 on D1−21; thereafter, only administration of MOR208 on D1 and D15 per cycle
• Data cut-off: 5 June 2018
• Median patient age (range) = 72 (41−87) years
• Number of patients who received ≥ 2 prior lines = 40%
• Median number of prior lines (range) = 2 (1−4)

Results

• Median follow-up = 12 months
• Median PFS = 16.2 months (95% CI, 6.3−not reached [NR])
• 12-month PFS = 50.1% (95% CI, 39.5−6%)
• By investigator assessment (intention-to-treat population):
• ORR = 58%
  • Complete response (CR) rate = 33% (n = 27)
    • PET/CT-confirmed CRs = 74%
    • CT-confirmed CRs = 26%
  • Partial response (PR) = 25% (n = 20)
  • Stable disease (SD) = 15% (n = 12)
  • Progressive disease (PD) = 19% (n = 15)
  • Not evaluable (NE) = 9% (n = 7)
  • 12-month DoR = 70%
  • Seventy percent of responding patients remained without progression at 12 months follow-up
• Median DoR = not reached (95% CI, NR−NR)
• A significant number of patients are still on study treatment (46%), with n = 19 having been treated for over 12 months
• Median OS = not reached (95% CI, 18.6−NR)
• 12-month OS = 73.3% (95% CI, 63.2−1%)
• The updated preliminary analysis shows a median PFS of 16 months

Safety

• No infusion-related reactions were reported for MOR208
• Treatment-related serious adverse events (AEs) occurred in n = 16 (19.8%) patients
  • The most common treatment-emergent AEs (any grade/grade ≥ 3) were:
    • Neutropenia: 48%/43%
    • Thrombocytopenia: 32%/17%
    • Anemia: 31%/9%
    • Diarrhea: 30%/1%
    • Pyrexia: 22%/1%
    • Asthenia: 20%/2%
  • Thirty-four patients (42%) required lenalidomide dose reduction
  • Fifty-eight (72%) patients could stay on daily lenalidomide of 20 mg or more
  • Three unrelated to study treatment deaths were reported:
    • Sudden death
    • Respiratory failure
    • Cerebrovascular accident

Conclusions

• MOR208 in combination with lenalidomide showed encouraging activity in R/R DLBCL patients with limited treatment options
• ORR was 58% and CR rate was 33%
• Hematological toxicities were manageable and MOR208 in combination with lenalidomide was well-tolerated
• Study is ongoing with the primary analysis expected in 2019