Capivasertib

Based on results of CAPItello-281 which prospectively defined PTEN-deficient disease and showed TRUQAP combination reduced risk of radiographic disease progression or death by 19% First-in-class AKT inhibitor moves into second tumor type to address an aggressive form of prostate cancer associated with poor prognosis WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca’s TRUQAP ® (capivasertib) in combination with abiraterone and prednisone has been approved in the US as the first and only targeted treatment for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer, previously referred to as metastatic hormone-sensitive prostate cancer (mHSPC), as detected by a US Food and Drug Administration (FDA)-authorized test. 1 The approval by the US FDA was based on positive results from the CAPItello-281 Phase III trial, presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in Annals of Oncology . 2 Prostate cancer is the second most prevalent cancer in men and the fifth leading cause of male cancer death globally, with more than 1.4 million people diagnosed each year. 3 Of these, approximately 200,000 patients worldwide, including 35,000 in the US, are diagnosed with mAPMN/S prostate cancer annually. 4 One in four of these patients have PTEN-deficient tumors, which fuels the growth of cancer cells and defines an aggressive form of the disease associated with poor outcomes. 4-7 PTEN deficiency is an independent risk factor regardless of other clinical characteristics, and can be identified by immunohistochemistry testing at time of diagnosis. 7 Daniel George, MD, Director of Genitourinary Oncology at Duke Cancer Institute and investigator for the CAPItello-281 trial, said: “Patients with PTEN-deficient metastatic hormone-sensitive prostate cancer, now called metastatic androgen pathway modulation-naïve or sensitive prostate cancer, experience faster progression and worse prognosis than those without PTEN deficiency. Keeping patients with this form of prostate cancer in remission and free from disease progression as long as possible is a high priority. Today’s landmark approval of the capivasertib combination as the first and only targeted treatment option for these patients represents a significant clinical advance with the potential to improve their lives and change the course of disease.” Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “CAPItello-281 showed that for the first time, we can target a key driver of this disease to bring meaningful benefit to the one in four patients with this form of prostate cancer who urgently need biomarker-directed therapies. Today’s approval makes clear the importance of testing for actionable biomarkers, including PTEN deficiency, in prostate cancer.” Results from the primary analysis of the CAPItello-281 Phase III trial showed a statistically significant 19% reduction in the risk of radiographic disease progression or death and a clinically meaningful improvement in median radiographic progression-free survival (rPFS) of 7.5 months with TRUQAP in combination with abiraterone and androgen deprivation therapy (ADT) versus treatment with abiraterone and ADT with placebo (based on a hazard ratio [HR] of 0.81; 95% confidence interval [CI] 0.66–0.98; p=0.034). Median rPFS was 33.2 months for the TRUQAP combination versus 25.7 months for the comparator arm. 2 While overall survival (OS) data were immature at the time of the primary analysis, results for OS numerically favored the TRUQAP combination versus the comparator arm. The trial will continue as planned to further assess OS as a key secondary endpoint. The safety pro TRUQAP in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known pro each medicine. Grade 3 or higher adverse events occurred in 67% of patients treated with the TRUQAP combination, with rash (12.3%) and hyperglycemia (10.3%) the most frequently reported. 2 Concurrently with this approval, the FDA also approved a companion diagnostic test to detect PTEN deficiency in tumors of patients with prostate adenocarcinoma. A regulatory application for the TRUQAP combination in this setting is under review in the EU based on the CAPItello-281 Phase III trial. IMPORTANT SAFETY INFORMATION ABOUT TRUQAP ® (capivasertib) tablets TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components. Hyperglycemia TRUQAP can cause severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes Metastatic HR-Positive, HER2-Negative Breast Cancer - In CAPItello-291, increased fasting glucose (FG) 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. Diabetic metabolic decompensation occurred in 0.6% of patients, including diabetic ketoacidosis in 0.3% - In the study, 12% (43/355) of patients who received TRUQAP had an anti-hyperglycemic medication regimen either initiated or changed, including treatment with insulin in 4.8% (17/355) of patients PTEN-Deficient Metastatic Androgen Pathway Modulation-Naïve or -Sensitive Prostate Cancer - In CAPItello-281, increased fasting glucose (FG) from baseline occurred in 69% of patients treated with TRUQAP, including 25% of patients with Grade 2 (FG >160 to 250 mg/dL), 12% with Grade 3 (FG >250 to 500 mg/dL), and 1.2% of patients with Grade 4 (FG >500 mg/dL) events - The median time to first occurrence of hyperglycemia was 71 days (range: 1 to 1454). Dose reduction for hyperglycemia was required in 8.7% of patients and permanent discontinuation was required in 2.4% of patients. Diabetic ketoacidosis occurred in 1.2% of patients - In the study, 41% (204/503) of patients who received TRUQAP had an anti-hyperglycemic medication regimen either initiated or changed, including treatment with insulin in 16% (81/503) of patients The safety of TRUQAP has not been established in patients with Type 1 diabetes or Type 2 diabetes that is uncontrolled or requiring insulin at baseline as these patients were excluded from clinical studies. Before initiating treatment with TRUQAP, test fasting glucose levels (FPG or FBG), HbA1C levels, and optimize fasting glucose. After initiating treatment with TRUQAP, monitor or self-monitor FG levels on Day 3 or 4 of the dosing week during weeks 1, 2, 4, 6, and 8; then monthly while on treatment with TRUQAP; and as clinically indicated. Monitor HbA1C levels every 3 months during treatment with TRUQAP and as clinically indicated. Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of FG levels. For patients who experience hyperglycemia during treatment with TRUQAP, monitor FG at least twice weekly, on days on and off TRUQAP, until FG decreases to baseline levels. During treatment with anti-diabetic medications, monitor FG at least once a week for 2 months, followed by once every 2 weeks, or as clinically indicated. Consider consultation with a healthcare practitioner with expertise in the treatment of hyperglycemia and initiation of FG monitoring at home for patients who have risk factors for hyperglycemia or who experience hyperglycemia. Advise patients on the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes. Withhold TRUQAP immediately when ketoacidosis is suspected. If ketoacidosis is confirmed, permanently discontinue TRUQAP. Withhold TRUQAP in clinical situations known to increase the risk of severe hyperglycemia or ketoacidosis (eg, suspected serious infection or acute illness). Based on the severity of hyperglycemia, withhold, reduce dose, or permanently discontinue TRUQAP. Diarrhea TRUQAP can cause severe diarrhea associated with dehydration Metastatic HR-Positive, HER2-Negative Breast Cancer - In CAPItello-291, diarrhea occurred in 72% of patients. Grade 3 or 4 diarrhea occurred in 9% of patients - The median time to first occurrence was 8 days (range: 1 to 519). In the study, dose reductions were required in 8% of patients, and 2% of patients permanently discontinued TRUQAP due to diarrhea. In patients with Grade ≥2 diarrhea (n=93) with at least 1 grade improvement (n=89), median time to improvement from the first event was 4 days (range: 1 to 154) - In the 257 patients with diarrhea, 59% required anti-diarrheal medications to manage symptoms PTEN-Deficient Metastatic Androgen Pathway Modulation-Naïve or -Sensitive Prostate Cancer - In CAPItello‑281, diarrhea of any grade occurred in 264 (52%) patients. Grade 3 occurred in 31 (6%) patients and Grade 4 occurred in 1 (0.2%) patient - The median time to first occurrence was 12 days (range: 3 to 48). In the study, dose reductions were required in 26 (5%) patients and 6 (1.2%) patients discontinued TRUQAP due to diarrhea - In the 264 patients with diarrhea, anti-diarrheal medication was required in 64% (170/264) of patients to manage diarrhea symptoms Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start anti-diarrheal treatment at the first sign of diarrhea while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. Cutaneous Adverse Reactions TRUQAP can cause cutaneous adverse reactions, which can be severe, including erythema multiforme (EM), palmar-plantar erythrodysesthesia (PPE), and drug reaction with eosinophilia and systemic symptoms (DRESS). Metastatic HR-Positive, HER2-Negative Breast Cancer - In CAPItello-291, cutaneous adverse reactions occurred in 58% of patients. Grade 3 or 4 cutaneous adverse reactions occurred in 17% of patients receiving TRUQAP. EM occurred in 1.7% of patients, and DRESS occurred in 0.3% of patients - The median time to onset of cutaneous adverse reactions was 13 days (range: 1 to 575 days). Dose reduction was required in 7% of patients and 7% of patients permanently discontinued TRUQAP due to cutaneous adverse reactions - Among the 204 patients with cutaneous adverse reactions, 44% (90/204) required corticosteroid treatment. Of these, 37% (76/204) were treated with topical corticosteroids and 19% (39/204) with systemic corticosteroids. In patients with Grade ≥2 cutaneous adverse reaction (n= 116) with at least 1 grade improvement (n=104), median time to improvement from the first event was 12 days (range: 2 to 544) PTEN-Deficient Metastatic Androgen Pathway Modulation-Naïve or -Sensitive Prostate Cancer - In CAPItello-281, cutaneous adverse reactions occurred in 53% of patients. Grade 3 cutaneous adverse reactions occurred in 84 (17%) patients and Grade 4 occurred in 1 (0.2%) patients - The median time to onset of rash was 13 days (range: 11 to 63 days). In the study, dose reduction was required in 58 (12%) patients and 38 (8%) patients discontinued TRUQAP due to rash - Among the 265 patients with cutaneous adverse reactions, 80% (212/265) required treatment and 91% (242/265) recovered in the study. Of these, 54% (115/212) were treated with topical corticosteroids and 25% (54/212) with systemic corticosteroids Monitor patients for signs and symptoms of cutaneous adverse reactions. Early consultation with a dermatologist is recommended. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. Embryo-Fetal Toxicity Based on findings from animals and mechanism of action, TRUQAP can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRUQAP and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRUQAP and for 4 months after the last dose. TRUQAP is used in combination with fulvestrant or abiraterone. Refer to the full Prescribing Information of fulvestrant or abiraterone for pregnancy and contraception information. ADVERSE REACTIONS Metastatic HR-Positive, HER2-Negative Breast Cancer - Among the 355 patients who received TRUQAP in CAPItello-291, the most common (≥20%) adverse reactions, including laboratory abnormalities, were diarrhea (72%), cutaneous adverse reactions (58%), increased random glucose (57%), decreased lymphocytes (47%), decreased hemoglobin (45%), increased fasting glucose (37%), nausea and fatigue (35% each), decreased leukocytes (32%), increased triglycerides (27%), decreased neutrophils (23%), increased creatinine (22%), vomiting (21%), and stomatitis (20%) - In the 155 patients with PIK3CA/AKT1/PTEN alterations treated with TRUQAP + fulvestrant, dose reductions due to adverse reactions were reported in 21% of patients. Permanent TRUQAP discontinuation due to an adverse reaction occurred in 10% of patients. Dose interruptions of TRUQAP occurred in 39% of patients PTEN-Deficient Metastatic Androgen Pathway Modulation-Naïve or -Sensitive Prostate Cancer - Among the 503 patients who received TRUQAP in CAPItello-281, the most common (≥20%) adverse reactions including laboratory abnormalities were increased fasting glucose (70%), decreased hemoglobin (61%), decreased lymphocytes (58%), cutaneous adverse reactions (53%), diarrhea (53%), decreased potassium (51%), increased creatinine (49%), increased non-fasting glucose (49%), increased alanine aminotransferase (38%), increased triglycerides (37%), increased aspartate aminotransferase (36%), decreased sodium (30%), and fatigue (26%) - In the 503 patients treated with TRUQAP + abiraterone and prednisone, dose reductions due to adverse reactions were reported in 32% of patients. Permanent TRUQAP discontinuation due to an adverse reaction occurred in 20% of patients. Dose interruptions of TRUQAP occurred in 65% of patients DRUG INTERACTIONS Strong CYP3A Inhibitors: Avoid concomitant use with a strong CYP3A inhibitor. If concomitant use cannot be avoided, reduce the dose of TRUQAP and monitor patients for adverse reactions. Moderate CYP3A Inhibitors: When concomitantly used with a moderate CYP3A inhibitor, reduce the dose of TRUQAP and monitor patients for adverse reactions. Strong or Moderate CYP3A Inducers: Avoid concomitant use of TRUQAP with strong or moderate CYP3A inducers. INDICATIONS AND USAGE - 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-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 - TRUQAP in combination with abiraterone and prednisone is indicated 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 Please see full Prescribing Information , including Patient Information for TRUQAP. Notes Prostate cancer In the US, prostate cancer is the most common cancer in men, with more than 300,000 new cases of the disease diagnosed annually, and more than 36,000 deaths. 8 Metastatic prostate cancer is associated with a significant mortality rate, with only one third of patients surviving five years after diagnosis. 9 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. 10 Metastatic androgen pathway modulation-naïve or sensitive prostate cancer mAPMN/S prostate cancer, previously referred to as mHSPC or metastatic castration-sensitive prostate cancer (mCSPC) reflects new, redefined terminology for clinical trials and regulatory indications in prostate cancer. 1 In patients with mAPMN/S prostate cancer, prostate cancer cells need high levels of androgens to drive cancer growth. 5,10 Hormone therapies, such as androgen deprivation therapies, are widely used to block the action of male sex hormones and lower the levels of androgens in the body. 5,10 However, resistance to these therapies is common and there is a need to extend their use to delay disease progression and castration resistance, where the prostate cancer grows and spreads to other parts of the body despite the use of these therapies. 5,6,11 mAPMN/S prostate cancer is an aggressive form of the disease associated with poor outcomes and survival. 5,6 Globally, approximately 200,000 patients are diagnosed with mAPMN/S prostate cancer each year, with 35,000 patients diagnosed with the disease in the US. 4 One in four of these patients have PTEN-deficient tumors. 4 PTEN-loss or deficiency fuels the growth of cancer cells, leading to dysregulation of the PI3K/AKT pathway, and is associated with poor outcomes in patients with prostate cancer. 12,13 CAPItello-281 CAPItello-281 is a Phase III, double-blind, randomized trial evaluating the efficacy and safety of TRUQAP ® (capivasertib) in combination with abiraterone and ADT versus abiraterone and ADT in combination with placebo in the treatment of patients with newly diagnosed PTEN-deficient mAPMN/S prostate cancer. The global trial enrolled 1,012 adult patients with histologically confirmed newly diagnosed APMN/S prostate adenocarcinoma and PTEN deficiency as confirmed by central testing. The primary endpoint of the CAPItello-281 trial is rPFS as assessed by investigator, with OS as a key secondary endpoint. TRUQAP ® (capivasertib) TRUQAP ® (capivasertib) is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms ( AKT1/2/3 ). TRUQAP 400 mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition. TRUQAP in combination with fulvestrant is approved in the US, EU, Japan, China and a number of other countries for the treatment of adult patients with HR-positive (or estrogen receptor-positive), HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations ( PIK3CA , AKT1 or PTEN ) following recurrence or progression on or after an endocrine-based regimen based on the results from the CAPItello-291 trial. TRUQAP is also approved in Australia for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine based regimen based on these trial results. TRUQAP is currently being evaluated in combination with established treatments for the 1st-line treatment of HR-positive breast cancer in the Phase III CAPItello-292 trial. TRUQAP was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited). AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca . References Armstrong A, et al. Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4. J Clin Oncol . 2026;44:1249-1265. Fizazi K, et al. Capivasertib plus abiraterone in PTEN-deficient metastatic hormone sensitive prostate cancer: CAPItello-281 phase III study. Ann Oncol 2026; 37(1):53-68. Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin . 2024 Apr 4. doi: 10.3322/caac.21834. Cerner CancerMPact database. Accessed June 2026. American Society of Clinical Oncology Educational Book. Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment. Available at: . Accessed June 2026. Hussain M, et al. Metastatic Hormone-Sensitive Prostate Cancer and Combination Treatment Outcomes A Review. JAMA Oncol . 2024;10(6):807-820. Jamaspishvili T, et al. Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol . 2018 April;15(4): 222–234. American Cancer Society. Key Statistics for Prostate cancer. Available at: . Accessed June 2026. Chowdhury S, et al. Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer: The Prostate Cancer Registry. Target Oncol. 2020;15(3):301-315. National Cancer Institute. Hormone Therapy for Prostate Cancer Fact Sheet. Available at: . Accessed June 2026. Cancer Research UK. Hormone therapy for metastatic prostate cancer. Available at: . Accessed June 2026. Cuzick J, et al. Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer. Br J Cancer . 2013;108(12):2582-2589. Gasmi A, et al. Overview of the Development and Use of Akt Inhibitors in Prostate Cancer. J Clin Med . 2021;11(1):160. US-113586 Last Updated 6/26 Contacts Media Inquiries Lauren-Jei McCarthy +1 347 918 7001 US Media Mailbox: usmediateam@astrazeneca.com