DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer

Jhaveri, K; Andr&#233;, F; Loi, S; Hamilton, E; Schmid, P; Anders, CK; Testa, L; Wildiers, H; Tseng, LM; Lu, YS; Park, YH; Im, SA; Chen, SC; Young, RR; Lloyd, C; Wrona, M; Zhang, C; Carroll, D

Author(s): Jhaveri, K; André, F; Loi, S; Hamilton, E; Schmid, P; Anders, CK; Testa, L; Wildiers, H; Tseng, LM; Lu, YS; Park, YH; Im, SA; Chen, SC; Young, RR; Lloyd, C; Wrona, M; Zhang, C; Carroll, D;
Details: Publication Year 2026-03-16,Volume 32,Issue #6,Page 1046-1058
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: Establish the safety, tolerability, and preliminary activity of trastuzumab deruxtecan (T-DXd) in combination with other anticancer therapies in human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). PATIENTS AND METHODS: DESTINY-Breast08 was a two-part, open-label, multicenter, phase Ib study. Patients with locally confirmed HER2-low mBC received T-DXd plus capecitabine, durvalumab + paclitaxel, capivasertib, anastrozole, or fulvestrant. Eligibility criteria for hormone receptor status varied across modules and between study parts. Primary objectives were safety/tolerability and determining recommended phase II doses (RP2D); secondary endpoints included objective response rate (ORR; per investigator). RESULTS: In the dose-finding phase, 37 patients were assigned to a module. RP2Ds were determined for T-DXd plus capecitabine, capivasertib, anastrozole, or fulvestrant. For strategic reasons, T-DXd + durvalumab + paclitaxel was not pursued beyond the dose-finding phase (n = 3). In the dose-expansion phase, 101 patients were assigned to a module. For T-DXd + capecitabine, grade ≥3 adverse events (AE) occurred in 55% (11/20) of patients, and the ORR was 60%. For T-DXd + capivasertib, grade ≥3 AEs occurred in 67.5% (27/40) of patients, and the ORR was 60%. For T-DXd + anastrozole, grade ≥3 AEs occurred in 47.6% (10/21) of patients, and the ORR was 71.4%. For T-DXd + fulvestrant, grade ≥3 AEs occurred in 55% (11/20) of patients, and the ORR was 40%. Adjudicated drug-related interstitial lung disease/pneumonitis events were reported for T-DXd + capecitabine (3/20; grade 2, n = 2; grade 5, n = 1), T-DXd + capivasertib (8/40; all grade ≤2), and T-DXd + fulvestrant (5/20; all grade 2). CONCLUSIONS: Safety results were generally consistent with known individual profiles for T-DXd and combination drugs. T-DXd plus capecitabine, capivasertib, anastrozole, or fulvestrant demonstrated preliminary clinical activity in patients with HER2-low mBC.
Publisher: American Association for Cancer Research
Keywords: Humans; Female; *Breast Neoplasms/drug therapy/pathology/genetics/metabolism; Middle Aged; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse; effects/administration & dosage; *Erb-b2 Receptor Tyrosine Kinases/metabolism/genetics; Aged; Trastuzumab/administration & dosage/adverse effects; Adult; Immunoconjugates/administration & dosage/adverse effects; Neoplasm Metastasis; Capecitabine/administration & dosage; Paclitaxel/administration & dosage; Camptothecin/analogs & derivatives
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-25-0874
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-25-0874
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-01-20 05:38:40

Last Modified: 2026-04-02 06:01:40