Novartis data highlight efficacy of Piqray in HR+/HER2- metastatic breast cancer with a PIK3CA driver mutation immediately post-CDK4/6 inhibition.

BYLieve is an ongoing Phase II, open-label, 3-cohort non-comparative study evaluating Piqray with endocrine therapy including men and pre- and postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (mBC) who have progressed on or after prior therapies, including CDK4/6 inhibitor plus endocrine therapy. These data were presented at the 2021 San Antonio Breast Cancer Symposium (SABCS) from December 7-10 2021.

Highlights from the BYLieve data presented at SABCS : i. BYLieve Cohort A (P1-18-03) : Updated safety and efficacy data after 18 months of follow-up showed median overall survival improvement of 26.4 months (95% CI: 21.0-30.5) for patients treated with Piqray plus fulvestrant immediately following CDK4/6 inhibitor plus an AI (aromatase inhibitor). The most common all-grade adverse events (AEs) (n=127) were diarrhea (63.8%), hyperglycemia (59.8%), nausea (46.5%) and rash (31.5%). ii BYLieve Cohort C (PD13-05): The third and final BYLieve cohort included patients who received chemotherapy or endocrine therapy as immediate prior treatment, who could have received prior CDK4/6 inhibitor as well. o The primary endpoint was met with 48.7% (95% CI: 39.3%-58.2%) of patients alive and without disease progression at six months. o Data confirm clinically relevant activity of Piqray as a targeted therapy for PIK3CA as a driver oncogene. o No new safety signals were observed, with the most common all-grade AEs (n=126) being hyperglycemia (65.1%), diarrhea (52.4%), nausea (40.5%) and rash (38.9%). iii. BYLieve Cohorts A & B (P1-18-08; P5-13-03; PD15-01) : Exploratory biomarker and post-hoc analyses demonstrated efficacy with Piqray plus fulvestrant/letrozole in CDK4/6 inhibitor-resistant mBC, as seen in patients with early discontinuation of the prior CDK4/6 inhibitor (Cohort A: less than 6 months median PFS of 12.0 months and greater than 6 months median PFS of 6.2 months; HR=0.51; 95% CI: 0.29-0.89; Cohort B: less than 6 months median PFS of 5.9 months and greater than 6 months median PFS of 5.6 months; HR=0.72; 95% CI: 0.45-1.18), supporting the use of Piqray plus endocrine therapy as an immediate next-line option in these patients. Grade greater than 3 AEs were experienced by 84.6% (n=22) and 66.0% (n=66) of patients in the less than 6 months and greater than 6 months subgroups, respectively, in Cohort A and by 62.5% (n=20) and 72.5% (n=66) of patients in the less than 6 months and greater than 6 months subgroups, respectively, in Cohort B3.

Additionally, the exploratory ctDNA analysis from Cohorts A and B (median PFS of 7.3 months and 5.7 months in Cohorts A and Cohort B, respectively) found that Piqray was effective in the post-CDK4/6 inhibitor setting regardless of endocrine therapy partner and tumor genomic profile and other mutations associated with CDK4/6 inhibitor resistance. Across the three cohorts no new safety signals were observed, even with longer exposure, as seen in Cohort A, confirming no cumulative toxicities with Piqray.

An estimated 361,826 people are diagnosed with mBC worldwide each year, and approximately 40% of those with HR+/HER2- subtype have a PIK3CA mutation, which is associated with a poor prognosis.

Note:CDK4/6 inhibitors are a newer class of medicines used to treat certain types of hormone-receptor-positive, HER2-negative breast cancer. These medicines interrupt the process through which breast cancer cells divide and multiply. To do this, they target specific proteins known as the cyclin-dependent kinases 4 and 6, abbreviated as CDK4/6. That is why they may be referred to as “targeted therapies. They include Ibrance (palbociclib) ,Kisqali (ribociclib) and Verzenio (abemaciclib)