TRUQAP® (capivasertib) recommended by FDA Advisory Committee for PTEN-deficient metastatic hormone-sensitive prostate cancer

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ODAC overwhelming majority voted that TRUQAP plus abiraterone and ADT demonstrated a favorable benefit risk profile for patients based on the CAPItello-281 Phase III trial results

First and only targeted treatment combination to demonstrate benefit in this subtype of prostate cancer addresses significant unmet patient need

WILMINGTON, Del.--(BUSINESS WIRE)-- The US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) has recognized a favorable benefit risk profile for AstraZeneca’s TRUQAP^® (capivasertib) in combination with abiraterone and androgen deprivation therapy (ADT) for the treatment of patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC), based on the CAPItello-281 Phase III trial. The Committee voted 7 to 1, with 1 abstaining.

In August 2025, the FDA accepted the supplemental New Drug Application (sNDA) for TRUQAP in combination with abiraterone and ADT based on positive results from the CAPItello-281 Phase III trial, presented at the 2025 European Society for Medical Oncology (ESMO) Congress and simultaneously published in Annals of Oncology.¹

Daniel George, MD, Director of Genitourinary Oncology at Duke Cancer Institute and investigator for the trial, said: “Patients identified to have PTEN-deficient metastatic hormone-sensitive prostate cancer have an aggressive form of the disease and currently experience poor outcomes. Their disease significantly impacts their quality of life and inevitably progresses to more advanced stages that are associated with high mortality rates. In addition to this poor prognosis, patients currently have limited treatment options, which is why today’s recommendation of the capivasertib combination is welcome news for both patients and clinicians to address an urgent need for new treatments that delay progression.”

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “CAPItello-281 is the first pivotal trial to prospectively define PTEN-deficient metastatic hormone-sensitive prostate cancer and its severe course of disease. The Committee’s recognition of the unmet need in patients with PTEN-deficiency and of the benefit seen with the TRUQAP combination verifies its potential to address this significant need and optimize outcomes for patients. We are committed to working closely with the FDA to bring the first and only targeted treatment option to the one in four patients with this form of metastatic hormone-sensitive 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 the TRUQAP combination 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.¹

A consistent benefit was observed with the TRUQAP combination versus treatment with abiraterone and ADT with placebo in key secondary endpoints of the trial, including prolonged time to castration resistance (29.5 vs. 22.0 months [HR 0.77; 95% CI: 0.63-0.94]) and prostate-specific antigen (PSA) progression (HR 0.73; 95% CI: 0.52-1.01), and fewer and delayed events in terms of symptomatic skeletal event-free survival (SSE-FS) (42.5 vs. 37.3 months [HR 0.82, 95% CI: 0.66-1.02]).¹

Overall survival (OS) data were immature at the time of primary analysis; however, subsequent interim 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 profile of TRUQAP in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each medicine. Consistent with the addition of a targeted treatment to background therapy, Grade 3 or higher adverse events occurred in 67% of patients treated with the TRUQAP combination versus 40.4% of patients treated with abiraterone and ADT with placebo. The most common Grade 3 or higher adverse events in the TRUQAP arm were rash (12.3%), hyperglycemia (10.3%), hypokalemia (8.7%), diarrhea (6.2%), hypertension (5.8%) and anemia (5.2%).¹

The ODAC provides the FDA with independent, expert advice and recommendations on marketed and investigational medicines for use in the treatment of cancer. The FDA will consider the feedback as it reviews the submission and is not bound by the Committee’s recommendation.

A regulatory application for TRUQAP in combination with abiraterone and ADT for the treatment of PTEN-deficient mHSPC 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

Severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes, can occur in patients treated with TRUQAP (n=355).

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 ketoacidosis occurred in 0.3% of patients and diabetic metabolic decompensation in 0.6% of patients.

In CAPItello-291, 12% (43/355) of patients who received TRUQAP had an anti-hyperglycemic medication either initiated or changed during the study, including treatment with insulin in 4.8% (17/355) of patients.

The safety of TRUQAP has not been established in patients with Type I diabetes or diabetes requiring insulin. Patients with insulin-dependent diabetes were excluded from CAPItello-291.

Before initiating treatment with TRUQAP, test fasting glucose levels (fasting plasma glucose or fasting blood glucose), hemoglobin A1C (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. Based on the severity of hyperglycemia, withhold, reduce dose, or permanently discontinue TRUQAP.

Diarrhea

Severe diarrhea associated with dehydration occurred in patients who received TRUQAP (n=355).

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 257 patients with diarrhea, 59% required antidiarrheal medications to manage symptoms. 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).

Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity.

Cutaneous Adverse Reactions

Cutaneous adverse reactions, which can be severe, including erythema multiforme (EM), palmar-plantar erythrodysesthesia, and drug reaction with eosinophilia and systemic symptoms (DRESS), occurred in patients who received TRUQAP (n=355).

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. Dose reduction was required in 7% of patients and 7% of patients permanently discontinued TRUQAP due to cutaneous adverse reactions.

Monitor patients for signs and symptoms of cutaneous adverse reactions. Early consultation with a dermatologist is recommended. Withhold, dose reduce, 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. Refer to the full Prescribing Information of fulvestrant for pregnancy and contraception information.

ADVERSE REACTIONS

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.

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.

INDICATION 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-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.

Please see full Prescribing Information, including Patient Information for TRUQAP.

Notes

Prostate cancer
Prostate cancer is the second most prevalent cancer in men and the fifth leading cause of male cancer death globally, with an incidence of more than 1.4 million and approximately 397,000 deaths in 2022.² 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.³

Metastatic prostate cancer is associated with a significant mortality rate, with only one third of patients surviving five years after diagnosis.⁴ Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.⁵

Metastatic hormone-sensitive prostate cancer
In patients with mHSPC, also known as metastatic castration-sensitive prostate cancer (mCSPC), prostate cancer cells need high levels of androgens to drive cancer growth.^5,6 Hormone therapies, such as ADT, are widely used to block the action of male sex hormones and lower the levels of androgens in the body.^6,7 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.^6-8

Newly diagnosed mHSPC is an aggressive form of the disease associated with poor outcomes and survival.^6,8 Globally, approximately 200,000 patients are diagnosed with mHSPC each year, with 35,000 patients diagnosed with the disease in the US.⁹ One in four of these patients have PTEN-deficient tumors.⁹

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.^10,11

CAPItello-281
CAPItello-281 is a Phase III, double-blind, randomized trial evaluating the efficacy and safety of TRUQAP in combination with abiraterone and ADT versus abiraterone and ADT in combination with placebo in the treatment of patients with PTEN-deficient de novo mHSPC.

The global trial enrolled 1,012 adult patients with histologically confirmed de novo hormone-sensitive 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 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 Phase III trials for the treatment of breast cancer (CAPItello-292) and prostate cancer (CAPItello-281) in combination with established treatments.

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).

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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.

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References

1. 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.
2. 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.
3. American Cancer Society. Key Statistics for Prostate cancer. Available at: https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html. Accessed April 2026.
4. 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.
5. National Cancer Institute. Hormone Therapy for Prostate Cancer Fact Sheet. Available at: https://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet. Accessed April 2026.
6. American Society of Clinical Oncology Educational Book. Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment. Available at: https://ascopubs.org/doi/pdf/10.1200/EDBK_390166. Accessed April 2026.
7. Cancer Research UK. Hormone therapy for metastatic prostate cancer. Available at: https://www.cancerresearchuk.org/about-cancer/prostate-cancer/metastatic-cancer/treatment/hormone-therapy-for-metastatic-prostate-cancer. Accessed April 2026.
8. Hussain M, et al. Metastatic Hormone-Sensitive Prostate Cancer and Combination Treatment Outcomes A Review. JAMA Oncol. 2024;10(6):807-820.
9. Cerner CancerMPact database. Accessed April 2026.
10. 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.
11. Gasmi A, et al. Overview of the Development and Use of Akt Inhibitors in Prostate Cancer. J Clin Med. 2021;11(1):160.

US-112424 Last Updated 4/26

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