Efficacy and safety of RC48-ADC in triple-negative breast cancer subtypes: FUSCC-TNBC-umbrella trial results.
Abstract
1109 Background: RC48-ADC is a novel HER2-targeting antibody-drug conjugate. This study evaluated RC48-ADC in pretreated triple-negative breast cancer (TNBC) patients with low HER2 expression, stratified by AR status. Methods: In this phase Ib/II trial, pretreated metastatic TNBC patients with low HER2 expression were enrolled: RL group (LAR subtype, n=20) and RO group (non-LAR subtype, n=20). All received RC48-ADC 2.0 mg/kg intravenously every 2 weeks. Primary endpoint: objective response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Results: 40 heavily pretreated patients were enrolled (median 2 previous lines, range 1-7). In the overall population, best ORR was 35.0% (confirmed ORR: 32.5%), DCR 47.5%, median PFS 4.0 months. RL group showed better outcomes: best ORR 45.0% vs 25.0%, confirmed ORR 40.0% vs 25.0%, DCR 50.0% vs 45.0%, median PFS 4.9 vs 3.1 months. Median OS was not reached in RL group vs 16.6 months in RO group. Most common treatment-related adverse events (TRAEs) were AST increased (70% vs 40%) and ALT increased (65% vs 20%), mostly grade 1-2. Peripheral neuropathy occurred in 15% (RL) and 10% (RO) patients. Hematologic toxicities were mild. No treatment-related deaths occurred. Conclusions: RC48-ADC showed promising antitumor activity with manageable safety in pretreated TNBC patients with low HER2 expression, particularly in LAR subtype. The 35.0% ORR in heavily pretreated TNBC warrants further investigation in biomarker-selected populations. Clinical trial information: NCT03805399 . Efficacy and key safety outcomes of RC48-ADC in overall population and by subgroups. Outcomes Overall (n=40) RL Group (n=20) RO Group (n=20) Efficacy Confirmed ORR, n (%) 13 (32.5) 8 (40.0) 5 (25.0) Best ORR, n (%) 14 (35.0) 9 (45.0) 5 (25.0) DCR, n (%) 19 (47.5) 10 (50.0) 9 (45.0) Median PFS, months 4 4.9 3.1 Median OS, months NR NR 16.6 Best Response, n (%) CR 1 (2.5) 1 (5.0) 0 (0.0) PR 13 (32.5) 8 (40.0) 5 (25.0) SD 5 (12.5) 1 (5.0) 4 (20.0) PD 21 (52.5) 10 (50.0) 11 (55.0) Selected TRAEs, n (%) AST increased - Grade 1-2 22 (55.0) 14 (70.0) 8 (40.0) - Grade ≥3 0 (0.0) 0 (0.0) 0 (0.0) ALT increased - Grade 1-2 17 (42.5) 13 (65.0) 4 (20.0) - Grade ≥3 0 (0.0) 0 (0.0) 0 (0.0) Peripheral neuropathy - Grade 1-2 3 (7.5) 2 (10.0) 1 (5.0) - Grade ≥3 2 (5.0) 1 (5.0) 1 (5.0)
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (7)
Yin Liu
Lin-Xiaoxi Ma
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
Lei Fan
Xi-Yu Liu
Fudan University Shanghai Cancer Center, Shanghai, China
Yi-Zhou Jiang
Key Laboratory of Breast Cancer in Shanghai, Shanghai institute of infectious Disease and Biosecurity, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University
Zhonghua Wang
Zhimin Shao
From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine–UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) — both in Pittsburgh; AGO-B and Helios Klinikum Berlin–Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie–Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen–EMN, Friedrich–Alexander University Erlangen–Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) — all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine,...