Itovebi

Itovebi is used to treat breast cancer that is HR-positive, HER-negative, has an abnormal PIK3CA gene, has spread, and has come back after treatment. Itovebi may help double progression-free survival when used in combination with palbociclib and fulvestrant, compared to using palbociclib and fulvestrant alone. Itovebi (inavolisib) tablets are taken once daily, with or without food, at about the same time each day.

Itovebi mechanism of action is as an inhibitor of PI3K mainly against PI3Kα, which results in slowing tumor growth and causing cancer cells to die. Itovebi class of medicines is a phosphatidylinositol 3-kinase (PI3K) inhibitor.

Itovebi FDA approval was received on October 10, 2024, for Genentech, Inc. a member of the Roche Group. Itovebi is used for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. It is used in combination with palbociclib (ibrance) and fulvestrant (Faslodex).

Itovebi FDA approval was based on positive results from the INAVO120 clinical trial (NCT04191499), which showed Itovebi-based regimen lowered the risk of cancer worsening or death occurring by 57% compared with palbociclib and fulvestrant alone. In this clinical study, the Itovebi-based regimen treatment group progression-free survival was 15.0 months compared to 7.3 months for the treatment group on palbociclib and fulvestrant alone.

HR-positive breast cancer is the most common type of breast cancer, accounting for approximately 70% of cases. HR-positive breast cancer has tumor cells that have receptors that attach to one or both hormones (estrogen or progesterone) which can help the tumor to grow. HR-positive metastatic breast cancer risks disease progression and treatment side effects, requiring additional treatment options. In HR-positive breast cancer, the PI3K signaling pathway often does not function properly, due to PIK3CA mutations. Mutations in the PIK3CA gene may cause the PI3K enzyme to become overactive, which may cause cancer cells to grow. Inavolisib works by blocking PIK3CA, which slows cancer growth

Take Itovebi tablet(s) once daily, at about the same time each day, with or without food.

Itovebi tablet(s) should be swallowed whole; do not chew, crush, or split the tablet(s).

If you vomit after taking your tablet(s), do not take an extra dose on that day. Take your regular dose of Itovebi at your usual time the next day.

Always take tablets exactly as your healthcare provider has told you to take them. You should not.

change your dose or stop taking tablets unless your healthcare provider tells you.

Itovebi is taken in combination with palbociclib and fulvestrant.

Also, see side effects section.

Embryo-Fetal Toxicity: This medicine can harm your baby. See pregnancy and fertility information for more details.

Before you take Itovebi, tell your healthcare provider about all of your medical conditions, including if you:

• have had or have had high blood sugar or a history or diabetes
• Have any kidney problems

Pregnancy and fertility

Tell your healthcare provider if you are are pregnant, plan to become pregnant or become pregnant during treatment as Itovebi can harm your unborn baby.

Information for Females who are able to become pregnant

Before you start treatment your healthcare provider will do a pregnancy test to see if you are pregnant.

You should use effective non-hormonal birth control (contraception) during treatment and for 1 week after your last dose of this medicine. Talk to your healthcare provider about what birth control method is right for you during this time.

Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Itovebi.

Males with female partners who are able to become pregnant:

You should use effective birth control (contraception) during treatment with Itovebi and for 1 week after your last dose.

General information on pregnancy and fertility. Itovebi is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for contraception and infertility information.

Based on animal studies, Itovebi may impair fertility in females and males of reproductive potential.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Itovebi passes into your breastmilk. Do not breastfeed during treatment with Itovebi and for 1 week after your last dose. Talk to your healthcare provider about the best way to feed your baby during treatment with Itovebi.

Common Itovebi side effects

The most common Itovebi side effects are headache, rash, nausea, diarrhea, loss of appetite, tiredness (faitgue), increase in blood sugar levels, COVID-19 infection, inflammed mouth (stomatitis), decreased neutrophils, decreased hemoglobin, decreased platelets, decreased lymphocytes, decreased calcium, decreased potassium, increased creatinine, increased ALT, decreased sodium, and decreased magnesium. These side effects occurred in 20% for more of patients in clinical trials when Itovebi was used

Serious Itovebi side effects

Itovebi may cause serious side effects, including high blood sugar levels (hyperglycemia), mouth sores, diarrhea and fertility issues.

High blood sugar levels (hyperglycemia). High blood sugar is common with this medicine and may be severe. Your healthcare provider will monitor your blood sugar levels before you start and during treatment with this medicine. Your blood sugar levels may be monitored more often if you have a history of Type 2 diabetes. Your healthcare provider may also ask you to self-monitor and report your blood sugar levels at home. This will be required more frequently in the first 4 weeks of treatment. If you are not sure how to test your blood sugar levels, talk to your healthcare provider. You should stay well-hydrated during treatment with this medicine. Tell your healthcare provider right away if you develop symptoms of high blood sugar, including:

• difficulty breathing
• blurred vision
• nausea and vomiting (lasting more than 2 hours)
• unusually increased appetite
• stomach pain
• weight loss
• excessive thirst
• fruity-smelling breath
• dry mouth
• flushed face and dry skin
• more frequent urination than usual or a higher amount of urine than normal
• feeling unusually sleepy or tired
• confusion

Mouth sores (stomatitis). Mouth sores are common with Itovebi and may be severe. Tell your healthcare provider if you develop any of the following in your mouth:

• pain
• swelling
• redness
• ulcers

Diarrhea. Diarrhea is common with Itovebi and may be severe. Severe diarrhea can lead to the loss of too much body water (dehydration) and kidney injury. Tell your healthcare provider right away if you develop diarrhea, stomach-area (abdominal pain), or see mucus or blood in your stool during treatment with this medicine. Your healthcare provider may tell you to drink more fluids or take medicines to treat your diarrhea.

Your healthcare provider may tell you to decrease your dose, temporarily stop your treatment, or completely stop your treatment if you develop certain serious side effects.

Fertility. Itovebi may affect fertility in males and in females who are able to become pregnant. Talk to your healthcare provider if this is a concern for you.

These are not all the possible side effects of Itovebi. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at (877) 436-3683.

The recommended Itovebi dose is 9 mg once daily.

Dose modification may be required due to adverse reactions or renal impairment. See Package Insert for more detailed information.

General dosing information

For women who have not reached menopause or are just starting menopause, your healthcare provider will prescribe a medicine called luteinizing hhormone-releasing hormone (LHRH) agonist.

For men, your healthcare provider may prescribe a LHRH agonist.

Palbociclib and fulvestrant dosing:

The recommended dosage of palbociclib is 125 mg taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a cycle of 28 days. Refer to the Full Prescribing Information for palbociclib and fulvestrant for dosing information.

Itovebi is available as 3 mg and 9 mg tablets

If you miss a dose of your tablet, you may still take your missed dose within 9 hours from the time you usually take it. If it has been more than 9 hours after you usually take your dose, skip the dose for that day. The next day, take the dose at your usual time.

Other drugs may affect this medicine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.

Store tablets at room temperature between 68°F to 77°F (20°C to 25°C).

Active ingredient: inavolisib

Inactive ingredients: lactose, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablet filmcoating contains iron oxide red, and iron oxide yellow (in the 9 mg tablet only), macrogol/polyethylene glycol, polyvinyl alcohol (partially hydrolyzed), talc, and titanium dioxide. Distributed by: Genentech USA, Inc., A Member of the Roche Group, 1

Itovebi by Genentech USA, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990