Table 1.

Overview of ERBB3 inhibitors

Name (antibody)TargetBiologic effectClinical status
MM-121 (SAR256212)ERBB3In combination with cetuximab, it blocks reactivation of ERBB3 in mice EGFR T790M-L858R, resulting in a sustained and durable response (31, 55, 56)
  • – Completed phase I safety and dose-finding trial

  • – Several phase I and phase II studies ongoing

  • – Refs 62–66

MM-111ERBB2 and ERBB3Antitumor activity in preclinical models that are dependent on ERBB2 overexpression (57)
  • – Completed phase I safety and dose-finding trial

  • – Several phase II studies ongoing

  • – Refs 52, 53

MM-141IGF-IR and ERBB3Prevents PI3K/AKT/mTOR network adaptation by blocking the redundant survival pathways and degrading the RTK complexes (58)
  • – Ongoing phase I study to establish the recommended dose and schedule

  • – Ref. 67

MEHD7945AEGFR and ERBB3It has superior antitumor activity against multiple tumor models compared with monospecific antibodies (59)
  • – Completed phase I safety and dose-finding trial, with evidence of anti-tumor activity

  • – Several phase I and phase II studies ongoing

  • – Ref. 68

LJM716ERBB3It inhibits ligand-induced and ligand-independent ERBB3 dimerization (60)
  • – Completed phase I safety and dose-finding trial, with evidence of antitumor activity

  • – Several phase I and phase II studies ongoing

  • – Refs 69, 70

RG7116 (RO5479599)ERBB3It inhibits xenograft tumor growth and downregulates cell surface ERBB3. Its efficacy is further enhanced in combination with anti-ERBB2 (pertuzumab) antibodies (61)
  • – Completed phase I safety and dose-finding trial, with evidence of antitumor activity

  • – Several phase I studies ongoing

  • – Ref. 71

U3-1287 (AMG 888, patritumab)ERBB3It blocks the upregulation of total and phosphorylated ERBB3 that follows treatment with lapatinib and trastuzumab, and enhances the antitumor action of the combination against trastuzumab-sensitive and -resistant cells (48)
  • – Completed phase I safety and dose-finding trial

  • – Several phase I, phase II, and phase III studies ongoing

  • – Ref. 72