First-Line Zanidatamab Plus Docetaxel in Advanced HER2-Positive BC

Preliminary results from an open-label phase 1b/2 trial (NCT04276493) showed that the novel HER2-targeted bispecific antibody zanidatamab plus docetaxel was associated with a manageable safety profile and demonstrated promising antitumor activity in patients with advanced HER2-positive breast cancer (BC). Updated results (after enrollment completion of cohort 1) of this trial were reported at the 2023 ASCO annual meeting.

In cohort 1, patients with advanced HER2-positive BC who may have received prior neoadjuvant/adjuvant therapy received zanidatamab plus docetaxel as first-line therapy. Investigators analyzed 2 intravenous (IV) doses of zanidatamab, 30 mg/kg (cohort 1a) and 1800 mg (cohort 1b), both with docetaxel 75 mg/m2 IV every 3 weeks. The primary end points were safety and investigator-assessed objective response rate (ORR) per RECIST version 1.1; secondary end points included investigator-assessed duration of response (DOR), disease control rate (DCR), progression free survival, and overall survival. The data cutoff date was November 22, 2022.

A total of 38 patients were enrolled, with 10 patients assigned to cohort 1a and 27 patients to cohort 1b; 1 patient was subsequently excluded due to nonmetastatic histology. At a median study follow-up of 15.5 months, patients had received a median of 13 treatment cycles, and 18 (48.6%) patients remained on treatment.

Of the total cohort of 33 patients who were evaluable for efficacy, 30 achieved a response for a confirmed ORR of 90.9%, including 2 complete responses (CRs), 28 partial responses (PRs), and 2 stable diseases (SDs); confirmed DCR was 97%, and median DOR was not estimable. In cohort 1a (n=8), confirmed ORR and DCR were 100%, including 1 CR and 7 PRs; median DOR was 12.4 months. In cohort 1b (n=25), confirmed ORR was 88%, including 1 CR, 21 PRs, and 2 SDs; confirmed DCR was 96% and median DOR was not estimable.

Safety analysis (N=37) reported treatment-related adverse events (TRAEs; ≥1) in nearly all patients (36/37; 97.3%). Of these, 25 (67.6%) patients experienced grade ≥3 TRAEs; the most common grade ≥3 TRAEs were decreased neutrophil count (48.6%) and decreased white blood cell count (18.9%). Serious TRAEs were reported in 6 (16.2%) patients; no TRAEs led to death.

Based on these results, the authors concluded that “Zanidatamab combined with docetaxel demonstrated promising antitumor activity as first-line therapy for advanced HER2-positive BC, with a manageable safety profile.”


Wang X, Lee KS, Zeng X, et al. 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. Abstract presented at: ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. Abstract 1044.

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