FDA ODAC Live Updates: Committee Weighs Data for Capivasertib Plus Abiraterone in PTEN-Deficient mHSPC

The second session of the April 30, 2026, meeting of the FDA’s Oncologic Drugs Advisory Committee (ODAC) is underway, as the group reviews results of the phase 3 CAPItello-281 trial (NCT04493853) supporting a supplemental new drug application seeking the approval of capivasertib (Truqap) in combination with abiraterone acetate (Zytiga) for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) that is PTEN-deficient as detected by an FDA-approved test.

Follow here for live updates over the course of the afternoon session, and check back for OncLive’s full story on ODAC’s vote immediately after the decision.

1:00 PM: The second session of the day is underway. If you missed the morning session and vote, read OncLive’s full story on the vote against the clinical benefit of camizestrant in the treatment of hormone receptor–positive breast cancer following the emergence of an ESR1 mutation ahead of radiographic progression during treatment with an aromatase inhibitor and a CDK4/6 inhibitor.

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In the second half of the April 30, 2026, meeting of the FDA’s Oncologic Drugs Advisory Committee (ODAC), the panel will consider results of the phase 3 CAPItello-281 trial (NCT04493853) supporting a supplement new drug application seeking the approval of capivasertib (Truqap) in combination with abiraterone acetate (Zytiga) for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) that is PTEN-deficient as detected by an FDA-approved test.¹

With ODAC set to delve into the CAPItello-281 data, discover the key question the committee will aim to address, along with previously reported findings that have emerged from the trial.

Stick with OncLive throughout the day on Thursday for live coverage of the meeting and a full breakdown of ODAC’s ultimate vote and its implications for capivasertib plus abiraterone for patients with PTEN-deficient mHSPC.

What question will ODAC address regarding data for capivasertib plus abiraterone for patients with PTEN-deficient mHSPC?

Following afternoon presentations from the FDA and AstraZeneca, the ODAC will vote on this question:^1,2

“Based on the CAPItello-281 results, does the benefit of adding capivasertib to abiraterone and prednisone outweigh the risk for the proposed indication?”

What data have been reported from the CAPItello-281 trial?

Findings published in Annals of Oncology demonstrated that patients with PTEN-deficient mHSPC treated with capivasertib plus abiraterone, prednisone/prednisolone, and androgen deprivation therapy (ADT; n = 507) achieved a median radiographic progression-free survival (rPFS) of 33.2 months (95% CI, 25.8-44.2) compared with 25.7 months (95% CI, 22.0-29.9) for patients treated with placebo plus abiraterone, prednisone/prednisolone, and ADT (n = 505; HR, 0.81; 95% CI, 0.66-0.98; P = .034).³

At the time of the trial’s primary analysis, data for overall survival (OS) reached 26.4% maturity, and a statistically significant difference was not observed between the 2 arms (HR, 0.90; 95% CI, 0.71-1.15; P = .401).

Patient-reported outcome (PRO) data reported at the 2026 Genitourinary Cancers Symposium showed that despite an increased rate of adverse effects (AEs) reported with the capivasertib combination, the regimen did not affect other functional aspects of patient life and overall health-related quality of life (HRQOL).⁴

Reported PRO outcomes included FACT-P physical well-being (least squares [LS] mean estimated difference, –0.4; 95% CI, –0.89 to 0.14), FACT-P functional well-being (LS mean estimated difference, –0.3; 95% CI, –1.01 to 0.37), and FACT-P total score (LS mean estimated difference, 0.4; 95% CI, –1.97 to 2.78).

The median time to clinically meaningful decrease in FACT-P physical well-being was 7.2 months (95% CI, 4.5-10.0) in the capivasertib arm vs 14.6 months (95% CI, 8.1-not calculable) in the placebo arm (HR, 1.43; 95% CI, 1.15-1.78). The median time to clinically meaningful decrease in FACT-P functional well-being was 6.3 months (95% CI, 4.4-10.9) vs 8.1 months (95% CI, 5.4-14.6), respectively (HR, 1.06; 95% CI, 0.86-1.32). The median time to clinically meaningful decrease in FACT-P total score was 9.0 months (95% CI, 6.3-20.1) in the capivasertib arm vs 12.7 months (95% CI, 8.1-21.9) in the placebo arm (HR, 1.10; 95% CI, 0.89-1.37).

How was the CAPItello-281 trial designed?

CAPItello-281 was a double-blind, placebo-controlled trial that enrolled patients at least 18 years of age with asymptomatic or mildly symptomatic, histologically confirmed de novo hormone-sensitive prostate adenocarcinoma without a small-cell component.⁵ Patients needed to be diagnosed within 180 days of randomization. PTEN deficiency per central immunohistochemistry testing was also required. Patients also needed to be candidates for abiraterone and steroid therapy.

Other key inclusion criteria comprised metastatic disease with at least 1 bone lesion and/or soft tissue lesion; an ECOG or WHO performance status of 0 or 1; and a life expectancy of at least 12 weeks.

Patients were randomly assigned 1:1 to receive capivasertib or placebo in combination with abiraterone, prednisone/prednisolone, and ADT.⁴ Capivasertib or placebo were administered at 400 mg twice per day on a 4-days-on, 3-days-off schedule. In both arms, patients received abiraterone at 1000 mg per day, prednisone/prednisolone at 5 mg per day, and ADT.

Investigator-assessed rPFS served as the trial’s primary end point. Secondary end points included OS, time to first subsequent therapy, symptomatic skeletal event–free survival, and time to pain progression.

What safety data were reported for capivasertib plus abiraterone?

Data from the primary analysis of CAPItello-281 showed that any-grade AEs occurred in 98.8% of patients in the capivasertib arm (n = 503) vs 92.0% of patients in the placebo arm (n = 503).³ The rates of grade 3 or higher AEs were 67.0% and 40.4%, respectively.

The most common any-grade AEs included diarrhea (capivasertib arm, 51.9%; placebo arm, 8.0%); hyperglycemia (38.0%; 12.9%), rash (35.4%; 7.0%), anemia (23.9%; 12.7%), hypokalemia (22.1%; 12.7%), hypertension (19.9%; 23.9%), fatigue (15.9%; 12.5%), increased alanine aminotransferase levels (14.1%; 13.3%), urinary tract infection (13.7%; 10.1%), increased aspartate aminotransferase levels (12.9%; 11.7%), nausea (12.1%; 4.4%), COVID-19 (11.7%; 8.7%), asthenia (11.3%; 5.0%), pyrexia (10.9%; 2.8%), hot flush (10.5%; 13.5%), pruritus (10.5%; 2.6%), back pain (9.9%; 10.9%), constipation (8.3%; 11.9%), arthralgia (7.6%; 10.1%).

References

1. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee. Draft agenda. FDA. Accessed April 29, 2026. https://www.fda.gov/media/192151/download
2. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee. Draft questions. FDA. Accessed April 29, 2026. https://www.fda.gov/media/192153/download
3. Fizazi K, Clarke NW, De Santis M, 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. doi:10.1016/j.annonc.2025.10.004
4. George DJ, Clarke NW, De Santis M, et al. Patient reported outcomes (PRO) and tolerability of capivasertib (capi) plus abiraterone (abi) versus placebo (pbo) plus abi in patients (pts) with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC): CAPItello-281. J Clin Oncol. 2026;14(suppl 7):14. doi:10.1200/JCO.2026.44.7_suppl.14
5. Capivasertib+abiraterone as treatment for patients with metastatic hormone-sensitive prostate cancer and PTEN deficiency (CAPItello-281). ClinicalTrials.gov. Updated April 1, 2026. Accessed April 29, 2026. https://clinicaltrials.gov/study/NCT04493853