A randomized, multicenter, double-blind, placebo-controlled phase III study of the efficacy and safety of trastuzumab emtasine in combination with atezolizumab or placebo in patients with HER2-positive and PD-L1-positive locally advanced or metastatic breast cancer who have received prior trastuzumab (+/-pertuzumab) and taxane-based therapy (PI: Olav Engebråten)

Inclusion Criteria:

  • HER2+ and PD-L1+ locally advanced (LABC) or metastatic breast cancer (MBC)
  • Progression must have occurred during most recent treatment for LABC/MBC or during, or within 6 months after completing, neoadjuvant and/or adjuvant therapy
  • Prior treatment with trastuzumab (+/- pertuzumab) and taxane in the neoadjuvant and/or adjuvant, locally advanced, or metastatic setting
  • No more than two prior lines of therapy in the metastatic setting
  • Measurable disease per RESIST version 1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy ≥ 6 months
  • Adequate hematologic and end-organ function
  • For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

  • Prior treatment with trastuzumab emtansine in metastatic setting
  • History of exposure to cumulative doses of anthracyclines
  • Symptomatic or actively progressing central nervous system (CNS) metastases; asymptomatic CNS lesions ≤ 2cm without clinical requirement for local intervention or asymptomatic patients with treated CNS lesions are eligible
  • Current Grade ≥ 3 peripheral neuropathy
  • Cardiopulmonary dysfunction
  • History of malignancy within 5 years prior to initiation of study treatment, with the exception of the cancer under investigation and malignancies with a negligible risk of metastasis or death
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • Active hepatitis B, hepatitis C and/or tuberculosis
  • Prior allogeneic stem cell or solid organ transplantation
  • Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, during treatment, or within 5 months following the last dose of study treatment
  • Pregnancy or lactation

Contact information: Olav Engebråten, olav.engebraten@rr-research.no