Preliminary results from ASCENT-J02: a phase 1/2 study of sacituzumab govitecan in Japanese patients with advanced...

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for metastatic triple-negative breast cancer (mTNBC) outside Japan.
• The ASCENT-J02 study (NCT05101096) evaluated SG safety and efficacy in Japanese patients with advanced solid tumors, including mTNBC.

Purpose of the Study:

• To establish the safety and efficacy of Sacituzumab govitecan (SG) in Japanese patients with previously treated metastatic triple-negative breast cancer (mTNBC).
• To determine the recommended phase 2 dose (RP2D) of SG in this patient population.

Main Methods:

• Phase 1 utilized a 3+3 design to assess safety and determine the RP2D, with dose escalation from 6 mg/kg to 10 mg/kg.
• Phase 2 enrolled patients with mTNBC who received SG at the RP2D (10 mg/kg) intravenously on Days 1 and 8 of a 21-day cycle.
• Primary endpoints included safety, dose-limiting toxicities (DLTs), RP2D, and independent review committee (IRC)-assessed objective response rate (ORR) using RECIST v1.1.

Main Results:

• The RP2D was determined to be 10 mg/kg of SG.
• In phase 2, 36 mTNBC patients received SG 10 mg/kg, achieving an IRC-assessed ORR of 25.0% (95% CI 12.1-42.2).
• Median progression-free survival was 5.6 months; median overall survival was not reached. No treatment-emergent adverse events led to discontinuation or death.

Conclusions:

• The recommended phase 2 dose of Sacituzumab govitecan (SG) was established at 10 mg/kg for Japanese patients.
• SG demonstrated significant efficacy in Japanese patients with previously treated mTNBC.
• SG exhibited a manageable safety profile with no new safety signals identified, consistent with prior studies.