201P Trilaciclib combined with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC): Preliminary phase II results

Trilaciclib protects CDK4/6-dependent hematopoietic stem and progenitor cells during chemotherapy (CT; myeloprotection). SG is an antibody–drug conjugate indicated to treat pts with mTNBC. In the phase III ASCENT trial, SG significantly extended survival vs single-agent CT but was associated with increased neutropenia (any grade [G], 63% vs 43%; G3/4, 51% vs 33%) and diarrhea (any G, 59% vs 12%; G3/4, 10% vs < 1%; Bardia et al. N Engl J Med. 2021). In a phase II trial of trilaciclib prior to CT in mTNBC, trilaciclib modulated antitumor immunity (Tan et al. Clin Cancer Res. 2022). Administering trilaciclib prior to SG may improve antitumor efficacy and minimize myelotoxicity in pts with mTNBC. We report preliminary safety and efficacy results from a phase II, single-arm trial of trilaciclib in pts receiving SG for mTNBC (NCT05113966). Eligible adult pts (≥ 2 prior systemic therapies [≥ 1 in the metastatic setting]; measurable disease; confirmed hormone receptor-/HER2-negative status; ECOG PS 0/1) receive intravenous trilaciclib 240 mg/m2 prior to SG 10 mg/kg on Days 1 and 8 of each 21-day cycle until disease progression/toxicity. Tumor assessments occur at screening, every 6 weeks to week 36, then every 9 weeks until disease progression/subsequent anticancer therapy. Endpoints include antitumor efficacy, myeloprotection, and safety/tolerability. As of January 17, 2023, 26 (of 45 planned) female pts had been enrolled and completed a median (range) of 4 (2–15) cycles. Pts had received a median of 2 (2–5) prior lines of therapy, including taxanes (n = 20) and immune checkpoint inhibitors (n = 18). See table; objective response rate by PD-L1 status will be presented. One pt had AEs that led to discontinuation of both study drugs. Table: 201PAEs (safety population; N = 26)Any G, n (%)G3/4, n (%)Selected AEs by preferred term (PT)FatigueNauseaAlopeciaConstipationDiarrheaHematological AEs by collapsed PTNeutropeniaAnemiaLeukopenia-11 (42)10 (39)8 (31)8 (31)8 (31)-6 (23)2 (8)4 (15)-01 (4)001 (4)-4 (15)03 (12)Best overall response (response-evaluable population; N = 20)n (%)95% CIComplete response (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD)Objective response rate (CR + PR)Clinical benefit rate (CR + PR + SD24wks)05 (25)*10 (50)5 (25)*5 (25)*7 (35)-8.7–49.127.2–72.88.7–49.18.7–49.115.4–59.2∗PR, n = 6 (30%); 1 pt with PR continued therapy after PD (21% increase in sum of longest diameters) Open table in a new tab ∗PR, n = 6 (30%); 1 pt with PR continued therapy after PD (21% increase in sum of longest diameters) Preliminary data suggest trilaciclib prior to SG has the potential to reduce the rate and severity of multiple AEs compared with results from trials of SG alone, and warrant its continued evaluation.