INAVO120 (Inavolisib + Palbociclib/Fulvestrant)
Architecture
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A Phase III, randomized, double-blind study evaluating inavolisib plus standard endocrine therapy in HR+/HER2– metastatic breast cancer with PIK3CA mutations.
Location
Global (US, UK, EU, Asia)
Category
Hudson Yards, New York
Year
2024
The INAVO120 trial enrolled 325 women with HR+/HER2– advanced breast cancer harboring PIK3CA mutations. Conducted across multiple regions—including the US, Europe, and Asia—the study tested the addition of inavolisib, a novel PI3Kα degrader, to palbociclib and fulvestrant. Treatment arms received inavolisib daily alongside palbociclib and fulvestrant, while the control arm received placebo with the same backbone. The trial innovatively incorporated translational research, assessing circulating tumor DNA for early response indicators and tracking pharmacokinetics to optimize dosing.
At a median follow-up of 21 months, progression-free survival (PFS) improved significantly in the intervention group—15.0 months versus 7.3 months in the placebo arm (hazard ratio 0.43; p < 0.001). Tumor response rates were similarly enhanced: 58.4% achieved an objective response compared to 25% for controls. Interim overall survival data trended favorably (HR 0.64), though final analysis is pending. These results are clinically meaningful, as delayed disease progression directly correlates with improved quality of life and prolonged survival outcomes.
Safety analysis and adverse event monitoring were central to trial evaluations. Most frequent side effects included neutropenia (88.9%), stomatitis (51%), and hyperglycemia (58%). Importantly, these events were effectively managed with dose adjustments or symptomatic care; only 6.8% of patients discontinued treatment due to adverse events. Quality-of-life assessments incorporated patient-reported outcomes, indicating that, despite some increased toxicity, the addition of inavolisib did not significantly impair overall patient well-being.
Based on these compelling results, the FDA granted Breakthrough Therapy Designation in May 2024, recognizing potential practice-changing benefit. Full approval followed in October 2024, making inavolisib the first PI3K degrader approved in this setting. Regulatory submissions are currently under review with the EMA, which may expand access across European markets should approval be granted.
