Meeting
2022 ASCO Annual Meeting
Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with docetaxel as first-line (1L) therapy for patients (pts) with advanced HER2-positive breast cancer: Preliminary results from a phase 1b/2 study.
Authors
Keun-Seok Lee
National Cancer Center, Center for Breast Cancer, Goyang, South Korea
Keun-Seok Lee , Xiaojia Wang , Young Hyuck Im , Xiaohua Zeng , Huiping Li , Kun Wang , Huiyan Li , Ping Zhou , Yuanyuan Bao , Zefei Jiang
Organizations
National Cancer Center, Center for Breast Cancer, Goyang, South Korea, Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, China, Department of Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Department of Breast Cancer Center, Chongqing University Cancer Hospital, Chonqqing, China, Department of Breast Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China, Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China, BeiGene Co., Ltd., Shanghai, China, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
Research Funding
Pharmaceutical/Biotech Company
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.
| Cohort A (n=9) | Cohort B (n=13) | Total (n=22) | |
|---|---|---|---|
| Confirmed best overall response, n (%) | |||
| Complete response | 1 (11.1) | 0 (0) | 1 (4.5) |
| Partial response | 7 (77.8) | 11 (84.6) | 18 (81.8) |
| Stable disease | 0 (0) | 1 (7.7) | 1 (4.5) |
| Progressive disease | 1 (11.1) | 1 (7.7) | 2 (9.1) |
| Confirmed ORR, n (%) 95% CI | 8 (88.9) 51.8, 99.7 | 11 (84.6) 54.6, 98.1 | 19 (86.4) 65.1, 97.1 |
| Confirmed DCR, n (%) 95% CI | 8 (88.9) 51.8, 99.7 | 12 (92.3) 64.0, 99.8 | 20 (90.9) 70.8, 98.9 |
| Confirmed DoR, range | 1.4–12.4 | 1.5–5.6 | 1.4–12.4 |
*Three pts without any post-baseline tumor assessments were excluded from EE analysis set.Data cut-off: Nov 26, 2021.
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Abstract Details
Session Type
Poster Session
Session Title
Breast Cancer—Metastatic
Track
Breast Cancer
Sub Track
HER2-Positive
Clinical Trial Registration Number
NCT04276493
Citation
J Clin Oncol 40, 2022 (suppl 16; abstr 1031)
DOI
10.1200/JCO.2022.40.16_suppl.1031
Abstract #
1031
Poster Bd #
409
Abstract Disclosures
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