Trilaciclib combined with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC): Updated phase 2 safety and efficacy results.
Year: 2024
Type: conference-abstract
Abstract: 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]
Source: Journal of Clinical Oncology
Authors: Lasika C. Seneviratne, Kathleen Kiernan Harnden, Sibel Blau, Michael A. Danso, David Berz, Delia Constanza Guaqueta, John F. Schwerkoske, Joyce O'Shaughnessy, Debra A. Patt, Aditya Bardia, Kelly Elizabeth McCann, Andrew Paul Beelen, Jingshan Zhang, John S. Yi, Sara A. Hurvitz, Mabel Alejandra Mardones
Institutions: Inova Fairfax Hospital, Northwest Medical Specialties, Virginia Oncology Associates, Memorial Regional Hospital, Minnesota Oncology, The US Oncology Network, University of California, Los Angeles, UCLA Jonsson Comprehensive Cancer Center, G1 Therapeutics (United States), University of Washington, Fred Hutch Cancer Center, Sarah Cannon, Rocky Mountain Cancer Centers
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: G1 Therapeutics
OpenAlex ID: W4399323701