Phase 3 InavoPC Trial of Inavolisib for mCRPC

A Phase 3 clinical trial is evaluating Inavolisib, a precision oncology drug, for men with metastatic castration-resistant prostate cancer (mCRPC).. The InavoPC trial offers a distinct approach: combining a PI3K inhibitor with continued hormonal therapy to address a fundamental biological mechanism of treatment resistance.

Inavolisib is a highly selective inhibitor of the PI3Kα kinase enzyme. The therapeutic rationale centers on the molecular crosstalk between two critical cancer-driving pathways: the androgen receptor pathway that fuels prostate cancer growth, and the PI3K-AKT-mTOR pathway that controls cell survival and proliferation. Approximately 40-60% of men with mCRPC harbor loss or inactivation of the PTEN tumor suppressor gene, which unleashes unopposed PI3K signaling and drives resistance to AR-directed therapies. By simultaneously targeting both pathways,using enzalutamide to block AR signaling combined with inavolisib to suppress PI3K signaling, tumors lose their ability to escape through either route.​

Inavolisib distinguishes itself through exceptional molecular selectivity. The drug is more than 300-fold selective for PI3Kα compared to related kinase isoforms, a critical feature because broad-spectrum PI3K inhibitors cause prohibitive toxicity through off-target effects. Inavolisib works through a dual mechanism: it competitively inhibits the catalytic activity of p110α and additionally triggers degradation of mutant p110α protein itself, effectively eliminating the driver of PI3K signaling in cancer cells. This selectivity preserves normal PI3K signaling in most cell types while selectively depleting oncogenic p110α activity.​

The drug has already demonstrated efficacy in breast cancer.

The InavoPC trial is a randomized, open-label Phase 3 study recruiting at approximately 200 clinical sites globally. Recruitment should start in March 2026.

Clinical trial.