KEY TAKEAWAYS
- The VELA phase I/II trial aimed to evaluate the safety, PK, PD, and efficacy of BLU-222 in advanced solid tumor pts.
- The dose was gradually increased to find the highest dose that pts could tolerate. Blood samples were taken to study the drug’s effects on the body.
- The study found that the BLU-222 was safe and effective in early trials. More studies are needed to find the best dose and to learn more about how it works.
Cyclin E and CDK2 are important for cell growth and division. Overexpression of cyclin E or CCNE1 gene amplification is common in aggressive cancers. In Advanced Solid Tumors, CDK2 inhibition is a promising new approach to treat cancer, especially cancers that have become resistant to CDK4/6 inhibitors.
Researchers aimed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of BLU-222 in advanced solid tumor patients (pts).
In a monotherapy dose-escalation study, adult pts, regardless of CCNE1 status, were included, specifically focusing on those with CCNE1 amplification or progression following a CDK4/6 inhibitor. Pts with ECOG PS 0–2 and unresectable tumors that had progressed after standard treatment for advanced relapsed/recurrent disease were enrolled. BLU-222 was given twice daily in continuous 28-day cycles, and dose escalation followed a Bayesian Optimal Interval design to determine the maximum tolerated dose(MTD). Blood samples were taken for pharmacokinetic and circulating biomarker analysis.
The study included 27 pts across six escalating BID dose cohorts, the safety population had a median age of 64 years (range: 29–85), with 85% being female. The most common cancer types were breast (44%, 12/27), endometrial (15%, 4/27), ovarian (11%, 3/27), and prostate (11%, 3/27). No pts discontinued treatment due to adverse events (AEs). The most frequent AEs (all-cause AE; treatment-related AE) were nausea (33%; 26%), vomiting (22%; 11%), anemia (22%; 19%), diarrhea (22%; 22%), and fatigue (18%; 15%). Transient visual AEs, including blurred vision, photophobia, and vision changes, were observed in 19% of pts with mild symptoms, except in one patient who experienced Grade 3 blurred vision/photophobia; all resolved by or after the data cut-off. Two dose-limiting toxicities(DLTs) were reported at the highest dose levels, which were nausea (Grade 3; n=1) and blurred vision/photophobia (Grade 3; n=1). Translational pharmacodynamic data indicated early evidence of pathway modulation. Notably, one partial response was observed in a patient with HR+/HER2− metastatic breast cancer who had previously undergone five lines of therapy, including palbociclib, abemaciclib, and capecitabine.
The study found that the BLU-222 was safe and effective in early trials. More studies are needed to find the best dose and to learn more about how it works.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.3095
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT05252416
Manish R. Patel, Dejan Juric, Brian S. Henick, Linda R. Duska, Rentian Wu, Jian Guo, Hui Zhang, Kate Newberry, Mikael Rinne, and Timothy A. Yap. DOI: 10.1200/JCO.2023.41.16_suppl.3095 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 3095-3095.
