Itovebi

In combination with palbociclib and fulvestrant for the treatment of adult patients with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after endocrine therapy.

Recommended dose: 9 mg orally once daily in combination with palbociclib 125 mg once daily for 21 days on/7 days off, and fulvestrant 500 mg IM on Days 1 and 15 of Cycle 1, then Day 1 of each subsequent 28-day cycle. Take inavolisib at approximately the same time each day with or without food.
Dose reduction: First to 6 mg; second to 3 mg. Discontinue if unable to tolerate 3 mg.

Tablets: 3 mg, 9 mg

None established in prescribing information.

• Hyperglycemia: Serious hyperglycemia including diabetic ketoacidosis (DKA) reported. Monitor fasting glucose before initiation, monthly for first year, and as clinically indicated. Optimize glycemic control before starting.
• Pneumonitis/ILD: Monitor for pulmonary symptoms. Withhold and investigate; permanently discontinue if Grade 3–4.
• Severe Cutaneous Adverse Reactions (SCAR): Stevens-Johnson syndrome and toxic epidermal necrolysis reported. Permanently discontinue if confirmed.
• Stomatitis: Manage with non-alcohol-containing mouthwash. Dose reduction may be needed.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise effective contraception during and after treatment.

Hyperglycemia (66%), Nausea (33%), Stomatitis (30%), Diarrhea (28%), Fatigue (27%), Neutropenia (76%), Decreased appetite (20%), Rash (18%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Strong CYP3A4 inhibitors: Increase inavolisib exposure; avoid or reduce inavolisib dose.
Strong CYP3A4 inducers: Decrease exposure; avoid concomitant use.
Antidiabetic agents: Monitor glucose closely; antidiabetic dose adjustments may be needed.

Can cause fetal harm. Advise females of reproductive potential to use effective contraception. Consult the full prescribing information for pregnancy risk details.

Advise women not to breastfeed during treatment and for a period after the last dose. Refer to prescribing information for duration guidance.

Safety and effectiveness in pediatric patients have not been established unless otherwise noted in the full prescribing information.

Dose modifications for organ impairment are specified in the complete prescribing information.

Inavolisib is a selective inhibitor of the phosphatidylinositol 3-kinase alpha (PI3Kα) isoform that also promotes degradation of mutant PI3Kα protein. PIK3CA mutations activate the PI3K/AKT/mTOR signaling pathway, driving cell proliferation. Inavolisib selectively blocks this pathway in tumor cells with PIK3CA mutations.

Tmax: ~2 hours. Protein binding: ~96%. Metabolized primarily by CYP3A4. Half-life: ~35 hours. Elimination: feces (~68%), urine (~13%). Steady state: ~8 days.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• INAVO120 — Inavolisib + palbociclib + fulvestrant vs placebo + palbociclib + fulvestrant in PIK3CA-mutated HR+/HER2- metastatic breast cancer. Phase III, n=325.
  🔬 NCT04191499 ↗📄 Primary Publication ↗

Itovebi has FDA-approved indications across the following cancer types covered on CancerDrugEvidence: