Blueprint Medicines to Present Leading Clinical Data on CDK2 and CDK4/6 Inhibitor Combo for HR+/HER2- Breast Cancer at 2024 ASCO

Blueprint Medicines Corporation has revealed updated findings from the Phase 1 dose escalation portion of the VELA clinical trial, which tested BLU-222—an investigational CDK2 inhibitor—in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. The data indicate that the combination therapy was well-tolerated at various active dose levels without any dose-limiting toxicities, and demonstrated early signals of clinical activity.

As of the data cutoff date, 19 patients with HR+/HER2- breast cancer, who had previously progressed on CDK4/6 inhibitors, received treatments of BLU-222 ranging from 100 mg to 400 mg twice daily, alongside 400 mg of ribociclib once daily and fulvestrant. The results showed that this combination was well-tolerated at all dose levels tested, with no treatment-related severe adverse events or discontinuations. Hematologic and gastrointestinal adverse events (AEs) were generally mild, and no maximum tolerated dose has yet been identified, allowing for ongoing dose escalation.

Pharmacokinetic analyses indicated dose-proportional exposures of BLU-222, with sustained drug levels above the efficacious concentration at the 400 mg BID dose. Importantly, the combination did not significantly impact the pharmacokinetics of the individual drugs involved.

Preliminary clinical activity revealed notable reductions in biomarkers thymidine kinase 1 (TK1) and circulating tumor DNA (ctDNA), which are known indicators of tumor cell proliferation and tumor burden, respectively. The most significant reductions in TK1 were observed in patients treated with the 400 mg BID dose of BLU-222 in combination with ribociclib and fulvestrant, correlating significantly with BLU-222 exposure. All patients with evaluable ctDNA treated with the highest dose regimen showed reductions in ctDNA levels. There was also an unconfirmed partial response in a patient who had previously undergone six lines of therapy, including prior palbociclib and trastuzumab deruxtecan.

Dr. Becker Hewes, Chief Medical Officer at Blueprint Medicines, highlighted the significance of these findings, stating, "Our selective CDK2 inhibitor BLU-222, in combination with ribociclib, shows a high level of tolerance and early evidence of clinical activity. This marks a significant milestone, suggesting that BLU-222 could become a crucial component in breast cancer treatment, especially in metastatic settings."

Detailed data will be presented by Dr. Dejan Duric from Massachusetts General Hospital during the "Breast Cancer – Metastatic" poster session at the 2024 ASCO Annual Meeting on June 2.

BLU-222, created by Blueprint Medicines, is a highly selective and potent CDK2 inhibitor with potential applications beyond HR+/HER2- breast cancer. It has shown promise in treating other cancers such as subsets of ovarian and endometrial cancer. CDK2, a cell cycle regulator, is often hyperactivated in various malignancies, leading to cell cycle dysregulation and tumor proliferation. Blueprint Medicines is also exploring additional CDK2 inhibitors and therapeutic candidates targeting cell cycle mechanisms.

Blueprint Medicines aims to address critical medical needs in oncology and hematology. With established research and development capabilities, the company continues to build a broad pipeline of programs, ranging from early-stage research to advanced clinical trials, with the goal of delivering life-changing therapies to patients worldwide.