Sacituzumab govitecan in Japanese participants with HR+/HER2− metastatic breast cancer: primary results from the phase II ASCENT-J02 study

Background Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved outside Japan for previously treated hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) unresectable locally advanced or metastatic BC (mBC) based on the global, phase III TROPiCS-02 study. ASCENT-J02 (NCT05101096; jRCT2031210346), an open-label, phase I/II study, evaluated efficacy and safety of SG in Japanese participants with advanced solid tumors. We report phase II HR+/HER2– mBC cohort primary results. Methods Participants with previously treated HR+/HER2– mBC received SG 10 mg/kg intravenously on days 1 and 8, every 21 days until progression/unacceptable toxicity. Primary endpoint: confirmed independent review committee (IRC)-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors v1.1), with 10% threshold (H0: ORR ≤10% vs H1: ORR >10%; one-sided P < .025). Key secondary endpoints: investigator-assessed ORR, IRC and investigator-assessed progression-free survival (PFS), overall survival (OS), safety. Results Forty-two participants received SG. At the 7.5-month median follow-up, ORR (95% CI) was 16.7% (7.0–31.4; P = .1214) by IRC and 28.6% (15.7–44.6) by investigator. Median PFS (95% CI) was 4.4 months (2.7–8.5) by IRC and 5.6 months (3.3–7.1) by investigator. Median OS (95% CI) was 13.0 months (11.0-not reached). Treatment-emergent adverse events (TEAEs) occurred in 41 (98%) participants (grade ≥ 3, 35 [83%]). No TEAE-related deaths reported; one participant discontinued treatment due to neutropenia. Conclusions Although the primary endpoint (ORR by IRC) was not met (P > .025), overall efficacy results were generally similar to TROPiCS-02, supporting access to SG in Japanese patients with HR+/HER2– mBC. Safety was consistent with the known and manageable SG safety profile.