Drug intelligence / Profile preview

pyrotinib + dalpiciclib + letrozole

Development stage
Phase 2
Lead developer
Hengrui Therapeutics
Modality
Small Molecules
Administration
Oral
01

Overview

This is a **chemotherapy-sparing, fully oral combination regimen** consisting of pyrotinib, dalpiciclib, and letrozole, developed for the treatment of **HER2-positive, hormone receptor-positive (HR-positive) metastatic breast cancer**. - **Pyrotinib** is an irreversible tyrosine kinase inhibitor targeting **HER2 (ERBB2)**, as well as EGFR and HER4, blocking downstream signaling and tumor cell growth. - **Dalpiciclib** is a selective **cyclin-dependent kinase 4/6 (CDK4/6) inhibitor**, preventing cell cycle progression from G1 to S phase through inhibition of CDK4/6-mediated phosphorylation of the retinoblastoma protein. - **Letrozole** is a non-steroidal aromatase inhibitor that suppresses estrogen synthesis, providing endocrine therapy in HR-positive malignancies. This triplet is being investigated as a **fully oral chemo-free first-line or second-line treatment** for postmenopausal women with HER2-positive, HR-positive metastatic breast cancer. The regimen demonstrates promising efficacy and manageable toxicity, with most common grade 3-4 adverse events being neutropenia, leukopenia, mucositis, and diarrhea. The combination is currently in Phase II trials[1][3][5].

Brand names
AiRuiNi
Other names
dalpiciclib + letrozole + pyrotinib
02

Targets

CYP19A1 (Aromatase)CDK4 (Cyclin-dependent kinase 4)CDK6 (Cyclin-dependent kinase 6)EGFR (Epidermal growth factor receptor)FGFR1 (Fibroblast growth factor receptor 1)FYN (Proto-oncogene tyrosine-protein kinase Fyn)ERBB2 (Erb-b2 receptor tyrosine kinase 2)ERBB4 (Erb-b2 receptor tyrosine kinase 4)NUAK1 (NUAK family SNF1-like kinase 1)PDGFRB (Platelet-derived growth factor receptor beta)RET (Rearranged during transfection receptor tyrosine kinase)ER (Estrogen receptor)

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