NDMM: early studies of frontline oprozomib hampered by GI toxicity

  • Hari P & al.
  • Blood Cancer J
  • 16 Aug 2019

  • curated by David Reilly
  • Univadis Clinical Summaries
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Takeaway

  • In patients with newly diagnosed multiple myeloma (NDMM), the second-generation proteasome inhibitor, oprozomib, demonstrated antimyeloma activity but gastrointestinal (GI) toxicities, and discontinuations were high.
  • A new formulation is to be studied in relapsed/refractory patients.

Why this matters

  • Continuous dosing is becoming common in NDMM, increasing needs for convenient oral regimens.

Study design

  • Phase 1b/2 studies to investigate oprozomib in 28 adult transplant-ineligible patients with NDMM:
    • Study OPZ003: oprozomib-dexamethasone+lenalidomide (ORd; 2 dosing schedules) or cyclophosphamide (OCyd; n=21).
      • 67 (range, 54-79) years median patient age.
    • Study OPZ006: oprozomib-melphalan-prednisone (OMP; n=7).
      • 71 (range, 66-84) years median patient age.
  • Funding: Onyx Pharmaceuticals, Inc.

Key results

  • In OPZ003:
    • 71.4% overall response rate (ORR); 38% ≥very good partial response; 2 patients achieved complete response (CR).
    • Incidence of grade ≥3 treatment-emergent adverse events (TEAEs) ranged from 66.7% to 100% across treatment arms.
    • 30.8% and 40% of patients discontinued from the 2 ORd arms due to AEs.
  • In OPZ006:
    • 42.9% ORR; 1 patient achieved CR.
    • 71.4% experienced grade ≥3 TEAEs.
    • 42.9% discontinued due to AEs.
  • GI AEs were the most common across studies.

Limitations

  • Limited sample size.