FDA ODAC Votes Yes to Capivasertib for PTEN-Deficient Metastatic HSPC

The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 7 to 1 in favor of the supplemental new drug application (sNDA) for capivasertib (Truqap) in patients 18 years and older with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (HSPC).¹

In the phase 3 CAPItello-281 trial (NCT04493853), capivasertib was evaluated with abiraterone acetate (Zytiga).² The proposed indication focuses on patients who are PTEN-deficient, as detected by an FDA-approved circulating tumor DNA (ctDNA) test.

“Overall, the totality of the data suggested clinical efficacy, clinical meaningfulness. The term clinical meaningfulness, we think about the primary end point, but we also thinak about how this drug would be deployed in the real world,” Neil Vasan, MD, PhD, director of Translational Research and assistant professor in the Department of Medicine at NYU Grossman School of Medicine, stated regarding his vote supporting the sNDA. “The conversations around toxicities, convincing that this is not only something that we as a field can manage but also something that would be tailored individually for a patient…those are the reasons that I voted ‘yes’”.

The CAPItello-281 Study

Supporting the sNDA, the CAPItello-281 trial findings showed improved radiographic progression-free survival (PFS) with capivasertib vs placebo, meeting its primary end point. According to the data previously presented at the 2026 ASCO Genitourinary Cancers Symposium, treatment with capivasertib significantly improved efficacy outcomes compared with placebo:

• Radiographic PFS: The median radiographic PFS was 33.2 months (95% CI, 25.8-44.2) with capivasertib vs 25.7 months (95% CI, 22.0-29.9) with placebo (HR, 0.81; 95% CI, 0.66-0.98; P = .032).
• PTEN loss and radiographic PFS (95%, 99%, and 100%): The median rPFS was consistent regardless of the extent of PTEN loss.
  • Among patients with at least 95% PTEN loss, the median radiographic PFS was 33.2 months with capivasertib vs 22.7 months with placebo (HR, 0.75; 95% CI, 0.60-0.94).
  • For those with at least 99% PTEN loss, the median radiographic PFS was 34.1 months vs 22.4 months (HR, 0.71; 95% CI, 0.52-0.97).
  • In those with complete PTEN loss, the median radiographic PFS was 34.1 months vs 22.1 months (HR, 0.68; 95% CI, 0.48-0.96).

Additionally, efficacy data published in the Annals of Oncology showed after a 26.4% maturity for overall survival (OS), the HR was 0.90 (95% CI, 0.71-1.11; P = .401).³

Study Schema

• Patient Population: Patients with metastatic HSPC demonstrated PTEN loss in at least 90% of cells by immunohistochemistry.
• Intervention: Patients were randomly assigned 1:1 to receive:

1. Capivasertib at 400 mg twice daily 4 days on and 3 days off plus once daily androgen deprivation therapy (ADT) at 1000 mg.
2. Matching placebo on the same 1000 mg once daily ADT schedule.

• Primary end point: radiographic PFS by investigator assessment
• Secondary end points: overall survival
• Exploratory end points: patient-reported outcomes and safety and tolerability

Clinical Characteristics and Safety Outcomes

Baseline characteristics were generally balanced between the capivasertib (n = 507) and the placebo arms (n = 505). The median age on trial was 67 years (range, 42-87) vs 68 years (range, 43-88), 52.5% vs 51.3% of patients were White, and 64.9% vs 63.4% had an ECOG performance status of 0. The most common sites of metastases were in the bones (91.1% vs 92.5%) and non-regional lymph nodes (42.8% vs 42.4%), most patients had a Gleason score of 8 or greater (78.5% vs 79.0%), and most patients had high-risk disease (61.3% vs 65.9%).

Overall, grade 3 or higher, and serious adverse effects (AEs) were observed at a greater frequency in the capivasertib arm, at rates of 98.8%, 67.0%, and 42.5% vs 92.0%, 40.4%, and 26.0% with placebo.

• Discontinuation resulting from AEs occurred in approximately 18% of patients treated with capivasertib vs 4.8% of those treated with placebo.
• The most common AEs with capivasertib included diarrhea (51.9%), hyperglycemia (38%), and rash (35.4%).

References

1. April 30, 2026 Meeting of the Oncologic Drug Advisory Committee (ODAC). Accessed April 30, 2026. https://tinyurl.com/5cry64pu
2. 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 Onc. 2026;44(suppl 7):14. doi:10. 10.1200/JCO.2026.44.7_suppl.14.
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