Abstract 42P
Background
FDA022-BB05 is an antibody-drug conjugate (ADC) composed of a humanized anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a DNA topoisomerase I inhibitor payload, with a high drug-to-antibody-ratio (DAR) of 8. Here, we report results from a phase I/Ib study of FDA022-BB05 in patients (pts) with unresectable, advanced, or metastatic solid tumors.
Methods
This phase I/Ib study comprises dose-escalation and dose-expansion phases. The escalation-phase followed an accelerated titration and traditional “3+3” design with five dose levels ranging from 1.6 to 8.0 mg/kg Q3W. In the dose-expansion phase, pts (ECOG 0-1) were eligible if they had HER2 positive breast cancer (BC), HER2 positive gastric/GEJ carcinoma, and were refractory or intolerant to standard therapy. Objectives included evaluating safety, maximum tolerated dose (MTD), or recommended phase II dose (RP2D) and preliminary antitumor activity.
Results
As of Aug 14 2024, 63 pts were enrolled. Of these pts, 76.2% had received two or more prior lines of systemic therapy. Treatment-emergent adverse events (TEAEs) and ≥ G3 TEAEs occurred in 63 pts (100%) and 42 pts (66.7%), respectively. The most common TEAEs included platelet count decreased (88.9%, 49.2%≥G3), white blood cell count decreased (87.3%, 17.5%≥G3), neutrophil count decreased (81.0%, 31.7%≥G3), anemia (81.0%, 17.5%≥G3). Treatment-emergent serious adverse events (SAEs) were reported in 25 pts (39.7%). 3 pts experienced dose-limiting toxicities (DLTs) characterized by G4 platelet count decreased at the 5.4mg/kg, 6.4mg/kg and 8.0mg/kg dose levels. No TEAE leading to death or interstitial lung disease were reported. Of 52 efficacy-evaluable pts with HER2-positive BC, the objective response rate (ORR) was 75.0% (39/52, 95% CI 61.05%-85.97%). At the dose of 5.4 mg/kg, the ORR was 85.3% (28/34, 95% CI 68.94%-95.05%) and the disease control rate (DCR) was 100.0%. Median progression-free survival (PFS) and overall survival (OS) were not reached.
Conclusions
FDA022-BB05 has demonstrated a manageable safety profile and quite promising antitumor activity in heavily pretreated HER2 positive BC. The study is still ongoing, while additional indications are being explored through other trials.
Clinical trial identification
NCT05564858.
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Fudan-Zhangjiang Biopharmaceutical Co., Ltd., Shanghai, China.
Funding
Shanghai Fudan Zhangjiang Bio-Pharmaceutical Co., Ltd.
Disclosure
Y. Yan, X. Wang, W. Sun, K. Liu: Financial Interests, Personal, Full or part-time Employment: Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.