434TiP - ALTER-BC-Ib-01: A prospective phase Ib study of anlotinib with trastuzumab deruxtecan (T-DXd) for HER2-low unresectable (u)/metastatic (m) breast cancer (BC)

Background

T-DXd significantly improved progression-free and overall survival in patients (pts) with HER2-low mBC in DESTINY-Breast04 trial. Anlotinib is a novel multitarget tyrosine kinase inhibitor that plays an effective role in suppressing new tumor vessel formation and enhancing blood perfusion and drug delivery by inducting tumor vascular normalization. We therefore hypothesized that combining anlotinib with T-DXd may exert a synergistic anti-neoplastic effect. This phase 1b study aims to evaluate the safety, tolerability and efficacy of anlotinib and T-DXd in HER2-low u/mBC.

Trial design

Eligible pts include those with pathologically documented HER2-low u/mBC (Low expression of HER2 was defined as an immunohistochemistry [IHC] score of 1+ or IHC 2+ with a negative in-situ hybridisation [ISH] score). Hormone receptor (HR)-positive pts whose disease had progressed on endocrine therapy (ET) in the metastatic setting. Pts with HR-negative or who were not eligible for ET had received less than 2 lines of prior chemotherapy for metastatic disease. Pts were ineligible if they had a history of noninfectious interstitial lung disease (ILD) that was treated with glucocorticoids or had suspected ILD on imaging at screening. The study consists of two phases: dose escalation and dose expansion. In the dose escalation phase, pts received dose escalation of anlotinib with three doses (8 mg, 10 mg, and 12 mg) orally once daily on day 8 to 21 every 3 weeks with T-DXd intravenously at doses of 5.4 mg/kg on day 1 every 3 weeks to determine the recommended phase 2 dose (RP2D) in a standard 3+3 design. In the dose expansion phase, pts received anlotinib at the RP2D + T-DXd 5.4 mg/kg combination therapy. Tumor assessment was performed every 2 cycles during the first 12 cycles, then every 3 cycles thereafter. The primary endpoints are RP2D and objective response rate. Secondary endpoints included duration of response, duration of response, progression-free survival, overall survival and safety. Study enrollment started in April 2022 and is ongoing.

Clinical trial identification

NCT06331169.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.