INAVO121 (Inavolisib vs Alpelisib + Fulvestrant)
Architecture
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A Phase III, head-to-head randomized trial comparing inavolisib versus alpelisib—each combined with fulvestrant—for advanced HR+/HER2– breast cancer with PIK3CA mutations.
Location
Global
Category
Hudson Yards, New York
Year
2024
The INAVO121 study is a pivotal comparative trial aiming to challenge the standard of care by evaluating inavolisib, a next-generation PI3Kα degrader, versus alpelisib, a well-established PI3Kα inhibitor. Like its predecessor, both treatment arms receive fulvestrant as backbone therapy. Trial designers hypothesize that the novel mechanism of targeted protein degradation may offer improved efficacy and a better safety profile over conventional enzymatic inhibition, especially by reducing the incidence of hyperglycemia and rash—common side effects seen with alpelisib.
Patient recruitment spanned major oncology hubs worldwide. Primary endpoints include progression-free survival, while critical secondary measures such as overall survival, safety, tolerability, and patient-reported outcomes are assessed meticulously alongside health economics data. The integration of biomarker sub-studies—analyzing PI3K pathway modulation and endocrine resistance pathways—adds a translational layer to this research. Data collection remains blinded, though early signals point to a favorable tolerability trend with inavolisib.
At year-end 2024, INAVO121 has enrolled a substantial proportion of the planned sample size, with top-line results anticipated in mid-2025. If inavolisib demonstrates superior or equivalent efficacy with improved safety, it may not only validate the drug's therapeutic potential but also reposition the PI3Kα treatment paradigm for HR+/HER2– breast cancer patients.
Given Roche’s broader strategy to cultivate a franchise around inavolisib, this trial’s outcome is pivotal. Positive results could catalyze additional studies and reposition the compound as a preferred alternative to alpelisib, influencing guidelines and clinical decision-making. Adverse-event profiles, dose modification rates, and quality-of-life outcomes will be key differentiators in determining the trial’s impact.
