Fig. 6: Fulvestrant enhances antitumor effects of BLU-222+ribociclib in ER+ breast cancer models.

a and b In vivo antitumor activity of BLU-222 (60 mg/kg BID [twice a day]), ribociclib (50 mg/kg QD [once a day]), fulvestrant (2.5 mg Q7D [once weekly]), or the combinations thereof. Mean tumor volume and SEM are plotted, n = 8 per group. a ST2056 is a model derived from a patient who had previously received abemaciclib+fulvestrant, and b ST941 is a model derived from a patient who had not received any prior lines of CDK4/6i therapy. For ST941, treatment ceased on day 31, and tumors were monitored for an additional 29 days to assess the durability of the response. Percent TGI was calculated using tumor volume from the final day of treatment: BLU-222, 41%; BLU-222 + fulvestrant, 80%; ribociclib+fulvestrant, 71%; BLU-222+ribociclib+fulvestrant, 97%. c Tumor growth relative to vehicle in PDX models categorized as CDK4/6i-experienced (model derived from a patient who had received prior lines of CDK4/6i therapy) or CDK4/6i-naïve (derived from a patient who had received no prior lines of CDK4/6i therapy). An additional three models in the PDX panel received BLU-222 + CDK4/6i + fulvestrant but did not receive ribociclib + fulvestrant as a comparator arm and therefore are not shown here (Supplementary Fig. S12). d Top 10 most enriched pathways from gene set enrichment analysis (GSEA) of differential gene expression between BLU-222+ribociclib+fulvestrant (triplet) and ribociclib + fulvestrant (duplet) in triplet responder PDX models that did not respond to the duplet. e Enrichment score relative to gene rank of Hallmark Interferon Alpha Response. f Enrichment score relative to gene rank of E2F Targets pathway genes.