| Autor: |
Naito, Yoichi, Nakamura, Seigo, Kawaguchi-Sakita, Nobuko, Ishida, Takanori, Nakayama, Takahiro, Yamamoto, Yutaka, Masuda, Norikazu, Matsumoto, Koji, Kogawa, Takahiro, Sudo, Kazuki, Shimomura, Akihiko, Lai, Catherine, Zhang, Danjie, Iwahori, Yuki, Gary, Dianna, Huynh, Danh, Iwata, Hiroji |
| Předmět: |
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| Zdroj: |
International Journal of Clinical Oncology; Nov2024, Vol. 29 Issue 11, p1684-1695, 12p |
| Abstrakt: |
Background: Sacituzumab govitecan (SG) is a Trop-2–directed antibody–drug conjugate approved outside Japan for second-line and later metastatic triple-negative breast cancer (mTNBC), based on the ASCENT study (NCT02574455). We report SG safety and efficacy in an open-label, phase 1/2 bridging study in Japanese patients with advanced solid tumors (ASCENT-J02; NCT05101096; jRCT2031210346). Methods: Phase 1 was a standard 3 + 3 design. Patients received intravenous SG 6 mg/kg, escalating to 10 mg/kg, on Days 1 and 8 per 21-day cycle; primary endpoints were safety, incidence of dose-limiting toxicity/toxicities (DLTs), and determination of the recommended phase 2 dose (RP2D). In the multicohort phase 2 study, patients in the mTNBC cohort with previously treated disease received SG at the RP2D; primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR; RECIST v1.1). Safety was a secondary endpoint. Results: In phase 1 (N = 15), one DLT (grade 3 elevated transaminases) occurred with SG 10 mg/kg; RP2D was SG 10 mg/kg regardless of UGT1A1 status. In phase 2, 36 patients with mTNBC received SG 10 mg/kg. At median follow-up of 6.1 months, IRC-assessed ORR was 25.0% (95% CI 12.1–42.2; P = 0.0077). Median progression-free survival was 5.6 months (95% CI 3.9–not reached [NR]); median overall survival was NR. No treatment-emergent adverse events led to discontinuation or death. Conclusions: SG RP2D was established as 10 mg/kg in Japanese patients. SG showed efficacy in Japanese patients with previously treated mTNBC, a manageable safety profile, and no new safety signals, consistent with the previous ASCENT study. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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