In a phase 1b trial, 82 patients with esophageal squamous cell carcinoma were treated with an anti-EGFR/HER3 bispecific antibody linked to a topoisomerase I inhibitor, at 2.0 or 2.5 mg/kg q3wks. Treatment response and drug Cmax were dose-related; overall response and disease control rates were 39.6/79.2% at 2.5mg/kg and 15/50% at 2 mg/kg. Although all patients experienced AEs, more strongly so at the higher dose, treatment was generally safe, and the 2.5mg/kg dose was selected for a Phase 2 trial. Pretreatment EGFR/HER3 expression did not correlate with treatment response (however most patients were positive).
Contributed by Alex Najibi
ABSTRACT: Research on patients with advanced esophageal squamous cell carcinoma (ESCC) who have progressed on immunotherapy remains limited. BL-B01D1 is a first-in-class antibody-drug conjugate consisting of an EGFR-HER3 bispecific antibody bound to a topoisomerase I inhibitor (Ed-04) payload via a cleavable linker. Here, we present safety and efficacy data from a phase 1 study of BL-B01D1, in 82 patients previously treated for ESCC. The primary endpoint was the recommended phase 2 dose. Administered doses were 2.0 (n = 22) and 2.5 (n = 60) mg kg-1 D1D8 infusion every 3 weeks (Q3W). The confirmed objective response rate (cORR) was 29.3% (24 of 82) in all patients and 32.9% (24 of 73) among evaluable patients. For patients dosed at 2.5 mg kg-1, cORR was 39.6% (21 of 53) and disease control rate was 79.2% (42 of 53). In the 2.0 mg kg-1 group, cORR was 15.0% (3 of 20), and the disease control rate was 50.0% (10 of 20). The phase 2 dose was established at 2.5 mg kg-1 D1D8 Q3W. The incidence of G3 treatment-related adverse events at 2.5 mg kg-1 was 63.3%; most common adverse events were anemia (28.3%), leukopenia and thrombocytopenia (18.3%, each), and neutropenia (16.7%). Two cases of ≥G3 interstitial lung disease were observed. Overall, BL-B01D1 demonstrated promising efficacy and manageable safety in patients with metastatic ESCC. A further phase 3 clinical trial has already been initiated. ClinicalTrials.gov registration: NCT05262491 .
Author Info: (1) Department of Early Drug Development Centre, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and
Author Info: (1) Department of Early Drug Development Centre, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (2) Department of Early Drug Development Centre, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (3) Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Henan, China. (4) Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Shandong, China. (5) Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Henan, China. (6) Department of Biological Therapy, West China Hospital of Sichuan University, Sichuan, China. (7) Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, China. (8) Department of Abdominal Radiotherapy, Zhejiang Cancer Hospital, Zhejiang, China. (9) Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (10) Department of Early Drug Development Centre, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China. (11) Department of Early Drug Development Centre, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (12) Department of Early Drug Development Centre, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (13) Department of Early Drug Development Centre, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (14) Department of Gastrointestinal Oncology, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China. (15) Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (16) Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (17) Department of Gastrointestinal Oncology, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China. (18) Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (19) Department of Gastrointestinal Oncology, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China. (20) Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. (21) Department of Gastrointestinal Oncology, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China. (22) Department of Gastrointestinal Oncology, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China. (23) Sichuan Biokin Pharmaceutical Co. Ltd., Chengdu, China. (24) Sichuan Biokin Pharmaceutical Co. Ltd., Chengdu, China. (25) Baili-Bio (Chengdu) Pharmaceutical Co. Ltd., Chengdu, China. (26) Department of Gastrointestinal Oncology, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China. goodjf@163.com. (27) Department of Gastrointestinal Oncology, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China. shenlin@bjmu.edu.cn. (28) Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. zhihaolupku@bjmu.edu.cn.
