Capivasertib

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 ).

• TRUQAP, in combination with fulvestrant, is indicated 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 -alteration as detected by an FDA-approved 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. TRUQAP is a kinase inhibitor indicated, 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-approved 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.ICD-10: C50.919

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

• 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 . ( 2.1 ) • Recommended Dosage: 400 mg orally twice daily, with or without food, for 4 days followed by 3 days off. ( 2.3 ) 2.1 Patient Selection 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 [see Clinical Studies (14) ] . Information on FDA-approved tests for the detection of PIK3CA, AKT1 , and PTEN alterations is available at: http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Evaluation Before Initiating TRUQAP Evaluate fasting blood glucose (FG) and hemoglobin A1C (HbA1C) prior to starting TRUQAP and at regular intervals during treatment [see Warnings and Precautions (5.1) ] . 2.3 Recommended Dosage and Administration The recommended dosage of TRUQAP, in combination with fulvestrant, is 400 mg orally twice daily (approximately 12 hours apart) with or without food, for 4 days followed by 3 days off. Continue TRUQAP until disease progression or unacceptable toxicity. TRUQAP dosing schedule for each week is provided in Table 1. Table 1: TRUQAP Dosing Schedule for Each Week Day 1 2 3 4 5 No dosing on day 5, 6 and 7. 6 7 Morning 2 x 200 mg 2 x 200 mg 2 x 200 mg 2 x 200 mg Evening 2 x 200 mg 2 x 200 mg 2 x 200 mg 2 x 200 mg Swallow TRUQAP tablets whole.

• Hyperglycemia: TRUQAP can cause hyperglycemia. Evaluate blood glucose levels prior to starting and at regular intervals during treatment. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. ( 2.2 , 2.4 , 5.1 ) • 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. ( 2.4 , 5.2 ) • Cutaneous Adverse Reactions: Monitor for signs and symptoms of cutaneous adverse reactions. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. ( 2.4 , 5.3 ) • Embryo-Fetal Toxicity: TRUQAP can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information. ( 5.4 , 8.1 , 8.3 ) 5.1 Hyperglycemia Severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes, can occur in patients treated with TRUQAP. Increased fasting glucose from baseline occurred in 37% of patients treated with TRUQAP, including 11% of patients with Grade 2 (FG > 160 to 250 mg/dL), 2% with Grade 3 (FG > 250 to 500 mg/dL), and 1.1% with Grade 4 (FG > 500 mg/dL) events. The median time to first occurrence of hyperglycemia was 15 days (range: 1 to 367). Dose reduction for hyperglycemia was required in 0.6% of patients and permanent discontinuation was required in 0.6% of patients.

The following adverse reactions are also discussed in greater details in other sections of the labeling: • Hyperglycemia [see Warnings and Precautions (5.1) ] • Diarrhea [see Warnings and Precautions (5.2) ] • Cutaneous Adverse Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥20%), including laboratory abnormalities, 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. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety population described in WARNINGS and PRECAUTIONS reflects exposure to TRUQAP 400 mg orally, twice a day for 4 days followed by 3 days off, in combination with fulvestrant, in 355 patients in CAPItello-291 until disease progression or unacceptable toxicity. Among the 355 patients who received TRUQAP, 52% were exposed for 6 months or longer, and 27% were exposed for greater than one year.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary TRUQAP is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for pregnancy information. Based on findings in animals and mechanism of action, TRUQAP can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of TRUQAP in pregnant women. In an animal reproduction study, oral administration of capivasertib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality and reduced fetal weights at maternal exposures 0.7 times the human exposure (AUC) at the recommended dose of 400 mg twice daily ( see Data ). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of capivasertib up to 150 mg/kg/day during the period of organogenesis.

Metabolism

Capivasertib pharmacokinetic parameters are presented as the mean [%coefficient of variation (%CV)], unless otherwise specified. The capivasertib steady-state AUC is 8,069 h·ng/mL (37%) and C max is 1,371 ng/mL (30%).

• Nov 16, 2023NDANDA218197Astrazeneca

1. 1Diarrhoea38216%
2. 2Death35715%
3. 3Rash34314%
4. 4Hyperglycaemia24810%
5. 5Nausea1365.7%
6. 6Malignant Neoplasm Progression1094.6%
7. 7Vomiting1084.6%
8. 8Fatigue1074.5%
9. 9Disease Progression1064.5%
10. 10Blood Glucose Increased1054.4%
11. 11Diabetic Ketoacidosis753.2%
12. 12Pyrexia753.2%
13. 13Decreased Appetite682.9%
14. 14Urinary Tract Infection602.5%
15. 15Dehydration592.5%

The 10 most recently updated of 65 ClinicalTrials.gov registrations naming Capivasertib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 435 enrolled · Stemline Therapeutics, Inc.
  NCT05563220updated 2026-06-12
• mTORC1/2 Inhibitor AZD2014 or the Oral AKT Inhibitor AZD5363 for Recurrent Endometrial and Ovarian
  Active not recruiting · Phase 1 · Interventional · 159 enrolled · M.D. Anderson Cancer Center
  NCT02208375updated 2026-06-12
• Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
  Recruiting · Phase 3 · Interventional · 540 enrolled · Relay Therapeutics, Inc.
  NCT06982521updated 2026-06-11
• First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
  Recruiting · Phase 1 · Phase 2 · Interventional · 880 enrolled · Eli Lilly and Company
  NCT05768139updated 2026-06-04
• Fast-Her: Fasting Effects on Breast Cancer Treatment
  Not yet recruiting · Interventional · 15 enrolled · University of Minnesota
  NCT07624617updated 2026-06-03
• Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
  Active not recruiting · Phase 2 · Interventional · 6,452 enrolled · National Cancer Institute (NCI)
  NCT02465060updated 2026-06-03
• Testing the Combination of Olaparib and Durvalumab, Cediranib and Durvalumab, Olaparib and Capivasertib, and Cediranib Alone in Recurrent or Refractory Endometrial Cancer Following the Earlier Phase of the Study That Tested Olaparib and Cediranib in Comparison to Cediranib Alone, and Olaparib Alone
  Active not recruiting · Phase 2 · Interventional · 288 enrolled · National Cancer Institute (NCI)
  NCT03660826updated 2026-06-02
• Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
  Recruiting · Phase 2 · Interventional · 124 enrolled · Alliance for Clinical Trials in Oncology
  NCT02523014updated 2026-06-02
• IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors
  Recruiting · Phase 1 · Interventional · 54 enrolled · M.D. Anderson Cancer Center
  NCT05039801updated 2026-06-01
• Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
  Recruiting · Phase 3 · Interventional · 895 enrolled · AstraZeneca
  NCT04862663updated 2026-05-27

Frequently asked questions

How does Capivasertib work?

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 ).

What is Capivasertib used for?

According to FDA labeling, Capivasertib carries indications including: TRUQAP, in combination with fulvestrant, is indicated 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 -alteration as detected by an FDA-approved 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. TRUQAP is a kinase inhibitor indicated, 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-approved 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Capivasertib?

Capivasertib is classified as Other protein kinase inhibitors, Serine/Threonine Kinase Inhibitors, Decreased Endothelial Proliferation.

What are the brand names for Capivasertib?

Capivasertib is marketed under brand names including Truqap.

What are the contraindications for Capivasertib?

Capivasertib labeling lists contraindications including: TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components. Severe hypersensitivity to TRUQAP or any of its components.. Always consult the full prescribing information and a clinician.