Globo H is a glycolipid that is highly expressed in breast cancer (BC). Active immunotherapy with OPT-822, a Globo H-KLH conjugate, and the adjuvant OPT-821 in two phase 1 trials, induced Globo H–specific antibodies which could mediate in vitro binding and cytotoxicity to Globo H expressing BC cells.
In this international, randomized, double-blind, placebo-controlled, phase 2/3 trial (NCT01516307), patients (pts) with metastatic BC who had ≤2 events of progressive disease (PD) and who achieved at least stable disease (SD) after ≥1 anticancer regimen were randomized 2:1 to receive subcutaneous OPT-822 (30 μg Globo H)/OPT-821 (100 μg) or control (PBS) on weeks 1, 2, 3, 5, 9, 13, 17, 25, and 37 or until PD, in combination with low-dose cyclophosphamide (300 mg/m2). Hormone therapy was allowed. The primary and secondary efficacy end points were progression-free survival (PFS) and overall survival (OS), correlated with humoral antibody response.
349 pts were randomized, 348 received study drug (ITT), 168 (48%) received all 9 injections. 70% had hormone receptor positive BC, 13% were triple negative, and 62% received hormone therapy. No difference was observed in PFS (HR=0.96 [95%CI 0.74-1.25] p=0.77); or in interim OS (HR=0.79 [95%CI 0.51-1.22] p=0.29). However, PFS and OS were significantly improved in the 50% of pts who developed a Globo H specific IgG response to OPT-822/OPT-821 with a titer ≥1:160 at any time during treatment vs control (HR=0.71 [95%CI 0.52-0.97] p=0.029 for PFS; HR=0.57 [95%CI 0.33-0.97] p=0.04 for OS) and vs nonresponders (HR=0.52 [95%CI 0.37-0.71] p<0.0001 for PFS, HR=0.52 [95%CI 0.29-0.92] p=0.025 for OS), adjusted for baseline disease status/hormone use. In a time dependent Cox model, PFS was improved in pts who received all 9 injections of OPT vs control (HR=0.66 [95%CI 0.42-1.01] p=0.057). OPT-822/OPT-821 was well tolerated; the most common drug-related adverse event was grade 1/2 injection reaction.
Vaccination with OPT-822/OPT-821 did not improve PFS in the ITT; however, PFS and interim OS were significantly improved in pts who developed an immune response to the vaccine. These subgroup data will be used to design a definitive Ph 3 trial.