Capivasertib

TRUQAP is a kinase inhibitor indicated: HR-Positive, HER2-Megative Locally Advanced or Metastatic Breast Cancer • in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations as detected by an FDA-authorized test following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy. PTEN-Deficient Metastatic Androgen Pathway Modulation-Naïve or -Sensitive (mAPMN/S) Prostate Cancer • in combination with abiraterone and prednisone for the treatment of adult patients with metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer that is PTEN-deficient as detected by an FDA-authorized test.

Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2 and AKT3) and inhibits phosphorylation of downstream AKT substrates. AKT activation in tumors is a result of activation of upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase ( PIK3CA ). In vitro, capivasertib reduced growth of breast cancer cell lines including those with relevant PIK3CA or AKT1 mutations or PTEN alteration. In vivo, capivasertib alone and in combination with fulvestrant inhibited tumor growth of mouse xenograft models including estrogen receptor positive breast cancer models with alterations in PIK3CA, AKT1, and PTEN. In vitro, capivasertib reduced growth of AR-positive PTEN deficient prostate cancer cell lines.

• Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with TRUQAP based on the presence of one or more of the following genetic alterations in tumor tissue: PIK3CA/AKT1/PTEN. • Select patients for the treatment of mAPMN/S prostate cancer with TRUQAP based on PTEN deficiency in tumor tissue. • Recommended Dosage: 400 mg orally twice daily, with or without food, for 4 days followed by 3 days off.

TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components. Severe hypersensitivity to TRUQAP or any of its components.

• Hyperglycemia: TRUQAP can cause severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes. Evaluate blood glucose levels and hemoglobin A1C prior to starting and at regular intervals during treatment. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. • Diarrhea: TRUQAP caused diarrhea in most patients. Advise patients to increase oral fluids, start antidiarrheal treatment, and consult with a healthcare provider if diarrhea occurs while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. • Cutaneous Adverse Reactions: Monitor for signs and symptoms of cutaneous adverse reactions. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. • Embryo-Fetal Toxicity: TRUQAP can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.

The following adverse reactions are also discussed in greater details in other sections of the labeling: • Hyperglycemia • Diarrhea • Cutaneous Adverse Reactions Most common adverse reactions (incidence ≥20%), including laboratory abnormalities, in patients with: • HR-positive, HER2-negative breast cancer were diarrhea, cutaneous adverse reactions, increased random glucose, decreased lymphocytes, decreased hemoglobin, increased fasting glucose, nausea, fatigue, decreased leukocytes, increased triglycerides, decreased neutrophils, increased creatinine, vomiting and stomatitis.

• Strong CYP3A Inhibitors: Avoid concomitant use. If concomitant use cannot be avoided, reduce TRUQAP dose. • Moderate CYP3A Inhibitors: Reduce TRUQAP dose. • Strong and Moderate CYP3A Inducers: Avoid concomitant use.

Store TRUQAP at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). Store tablets in the original package.