Trilaciclib combined with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC): Updated phase 2 safety and efficacy results.

1091 Background: Trilaciclib, a reversible cyclin-dependent kinase 4/6 inhibitor, protects hematopoietic stem and progenitor cells during chemotherapy (myeloprotection). In a phase 2 trial in mTNBC (NCT02978716), administering trilaciclib prior to chemotherapy enhanced T-cell activity and modulated antitumor immunity. In a phase 3 trial (ASCENT; NCT02574455), the antibody–drug conjugate SG significantly extended overall survival (OS) versus single-agent chemotherapy (12.1 vs 6.7 months) but was associated with increased neutropenia (any grade, 63% vs 43%; grade 3/4, 51% vs 33%) and diarrhea (any grade, 59% vs 12%; grade 3/4, 10% vs < 1%). This phase 2 single-arm trial was designed to assess safety and efficacy of trilaciclib prior to SG in mTNBC (NCT05113966). Methods: Eligible patients (≥ 2 prior systemic therapies [≥ 1 in the metastatic setting]; measurable disease; confirmed hormone receptor- and human epidermal growth factor receptor 2-negative status; Eastern Cooperative Oncology Group performance status 0 or 1) received intravenous trilaciclib 240 mg/m2 prior to SG 10 mg/kg on days 1 and 8 of each 21-day cycle until disease progression or toxicity. Tumor assessments occurred at screening, every 6 weeks through week 26, then every 9 weeks until disease progression or subsequent anticancer therapy. Endpoints included antitumor efficacy, myeloprotection, and safety and tolerability. Results: As of January 2, 2024, 30 female patients had been enrolled (median age, 56 years) and completed a median 6 (range, 2–29) cycles. Median follow-up was 11.2 months. Safety is summarized in the Table. The confirmed overall response rate (95% CI) was 23.3% (9.9–42.3), the clinical benefit rate was 46.7% (28.3–65.7), and the median duration of response was 9.1 (4.0–not estimable) months. Median progression-free survival was 4.1 (2.2–7.3) months. OS data are not yet mature; currently, median OS among patients receiving trilaciclib prior to SG is 17.9 (9.9–not estimable) months. Conclusions: Adding trilaciclib prior to SG reduces the rate and severity of multiple adverse events, notably neutropenia and diarrhea, compared with results from trials of SG alone. Preliminary data suggest clinically meaningful OS outcomes among patients receiving trilaciclib prior to SG compared with historical data for SG alone; however, caution should be exercised when interpreting results from cross-trial comparisons. Mature OS data will be presented. Clinical trial information: NCT05113966 . [Table: see text]