Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with docetaxel as first-line therapy (1L) for patients (pts) with advanced HER2-positive breast cancer (BC): Updated results from a phase 1b/2 study

1031 Background: HER2-targeted agents have improved outcomes in HER2-positive breast cancer, but some pts develop resistance, relapse, or do not respond to current 1L therapies. Zani, also known as ZW25, is a novel HER2-targeted bispecific antibody that binds to two distinct extracellular domains of HER2. In a Phase 1 trial (NCT02892123) zani was well tolerated and demonstrated preliminary antitumor activity as monotherapy/with chemotherapy in pts with pre-treated advanced HER2+ breast cancer. Methods: Cohort 1 of this ongoing open-label, Phase 1b/2 study (NCT04276493) is evaluating zani in combination with docetaxel as a 1L therapy in adult females with advanced HER2+ breast cancer who may have received prior neoadjuvant/adjuvant treatment. Cohort A pts received zani 30 mg/kg IV, Cohort B pts received zani 1800 mg IV, both with docetaxel 75 mg/m2 IV Q3W. Primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS). Results: As of Nov 26, 2021, 25 pts with a median age of 57.0 years (range: 33.0–80.0) were assigned to Cohort A (n=11) or B (n=14). Median study follow-up was 7.0 months (range: 1.1–17.4) and the median number of treatment cycles was 10 (range: 2–20), 16 (64.0%) pts remained on treatment. Of the 22-efficacy evaluable (EE) pts, confirmed ORR was 86.4% (95% CI: 65.1, 97.1). The 6 months PFS rate was 90.9% (95% CI: 68.3, 97.7). Efficacy data are summarized in Table 1. All pts experienced ≥ 1 treatment emergent adverse event (TEAE) and 17 (68.0%) pts experienced ≥ Grade 3 TEAEs. In total, 23 (92.0%) pts experienced treatment related TEAEs (trTEAEs), and 17 (68.0%) pts experienced ≥ Grade 3 trTEAEs. The most common trTEAEs were diarrhea (56.0%) and decreased neutrophil count (52.0%). Serious trTEAEs occurred in two (8.0%) pts, trTEAEs leading to treatment discontinuation occurred in one (4.0%) pt and no trTEAEs led to death. Conclusions: Zani and docetaxel combination demonstrated antitumor activity in 1L therapy for advanced HER2+ breast cancer, with a manageable safety profile. Clinical trial information: NCT04276493. [Table: see text]