G1 Therapeutics presents post hoc analyses on trilaciclib with chemotherapy

G1 Therapeutics announced the presentation of new data describing the long-term positive survival impact of previous treatment with trilaciclib and cytotoxic chemotherapy in patients with metastatic triple negative breast cancer who participated in G1’s Phase 2 trial. The poster is being presented at the 2023 San Antonio Breast Cancer Symposium, held December 5th to 9th in San Antonio, TX, and is available on the G1 Therapeutics website. The poster entitled, “Patients with Metastatic Triple-Negative Breast Cancer Who Receive Trilaciclib Prior to Cytotoxic Chemotherapy Exhibit Improved Survival After Receiving Subsequent Anticancer Therapy” describes a post hoc analysis of data from G1 Therapeutics’ randomized Phase 2 mTNBC trial indicating that patients with mTNBC who received trilaciclib with their cytotoxic chemotherapy during the trial and then received subsequent anticancer therapy after trilaciclib discontinuation exhibit statistically significant and clinically meaningful improvements in median overall survival and in median OS from start of first SACT compared to those who received cytotoxic chemotherapy without trilaciclib and then received SACT. Administering trilaciclib with cytotoxic chemotherapy also led to improved survival in patients unable to receive SACT. The Phase 2 trial enrolled patients who had received up to two prior chemotherapy regimens for locally recurrent or mTNBC. Participants were randomized into three groups: GCb alone on days 1 and 8, trilaciclib prior to GCb on days 1 and 8, or trilaciclib alone on days 1 and 8 and prior to GCb on days 2 and 9. G1 conducted a post hoc survival analysis on data from patients in this Phase 2 TNBC trial who received additional anticancer therapies after discontinuation of study treatment with GCb with or without trilaciclib, to evaluate improvements in long-term outcomes; the two trilaciclib groups were combined for this analysis. The SACTs administered include gemcitabine, capecitabine, eribulin, taxane, carboplatin, and PD-1/PD-L1 inhibitors. Additionally, murine cancer models were utilized to quantify the infiltration of central memory T cells in the tumor microenvironment seven days after a single dose or seven daily doses of trilaciclib. Memory T cell recall responses were also evaluated. Survival Outcomes: After a median follow-up of 12.7 months on study, deaths were observed in 22/43 patients in the trilaciclib plus GCb group and 17/20 patients in the GCb-only group. Median time on treatment was 5.5 months in the trilaciclib plus GCb group and 3.3 months in the GCb-only group. Patients receiving SACT following trilaciclib plus GCb exhibited statistically significant improvements in median OS compared to those receiving SACT following GCb alone, with increasing separation of survival curves over time. Median OS and progression-free survival were higher in the prior trilaciclib plus GCb group compared with the prior GCb-only group, regardless of the type of SACT received. Improved survival and sustained separation of curves were also observed in patients unable to receive SACT although the magnitude of benefit was smaller. Patients receiving SACT following trilaciclib plus GCb also exhibited statistically significant improvements in median OS from start of the first SACT compared to those receiving SACT following GCb alone. Immune Surveillance Results In addition, data from murine models indicate that trilaciclib-mediated transient cyclin-dependent kinase 4/6 inhibition may enhance tumor infiltration of CD8+ central memory T cells and boost memory T cell recall responses, further clarifying the mechanism by which trilaciclib improves long-term immune surveillance: Compared with daily dosing, a single dose of trilaciclib resulted in an increase in the number of tumor infiltrating CD8+ central memory T cells in the tumor microenvironment on day seven. Administering trilaciclib enhanced the efficacy of combination immunotherapy with alpha-PD-1 plus alpha-LAG3; seven of eight mice that received trilaciclib plus alpha-PD-1 and alpha-LAG3 survived compared to three of eight mice that received treatment with alpha-PD-1 plus alpha-LAG3. Following rechallenge in the opposite flank of the surviving mice, tumors implanted in those previously treated with trilaciclib grew to a smaller volume and regressed faster than controls, demonstrating the ability of trilaciclib to strengthen memory T cell recall responses.