A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib + Abiraterone Versus Placebo + Abiraterone as Treatment for Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Characterised by PTEN deficiency (CAPItello-281)

- Asymptomatic or mildly symptomatic, histologically-confirmed de novo
metastatic hormone-sensitive prostate adenocarcinoma without smallcell tumours
- Provide a FFPE tissue block (preferred) or slides. Tissue from bone
metastases is not acceptable
- A valid PTEN IHC result indicating PTEN deficiency (centralized testing)
- Metastatic disease documented prior to randomisation by clear evidence of >= 1
bone lesion and/or >= 1 soft tissue lesion accurately assessed at baseline and
suitable for repeated assessment with CT and/or MRI.
- Candidate for abiraterone and steroid therapy
- Ongoing ADT with GnRH analogue, or LHRH agonists or antagonist, or bilateral
orchiectomy
- Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0 to 1 with
no deterioration over the previous 2 weeks and minimum life expectancy of 12
weeks
- Able and willing to swallow and retain oral medication
- 7-day Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue
Inventory(BFI) questionnaires and the analgesic diary during screening
completed

-Prior radical prostatectomy or definitive radiotherapy with a therapeutic
intent for prostate
cancer. Palliative radiotherapy is allowed providing any wide field of
radiation therapy
(eg, more than one-third of the skeleton) withinis completed more than 4 weeks
before the
start of study treatment (capivasertib/placebo).

-Major surgery (excl.placement of vascular access,transurethral resection of
prostate,bilateral orchiectomy,internal stents) within 4 wks of start of study
treatment
-Brain metastases,or spinal cord compression (unless spinal cord compression is
asymptomatic, treated and stable and not requiring steroids for at least 4 wks
prior to start of study treatment)
-Past medical history of interstitial lung disease,drug-induced interstitial
lung disease,radiation pneumonitis which required steroid treatment,or any
evidence of clinically active interstitial lung disease
-Any of the following cardiac criteria:
i.Mean resting corrected QT interval (QTc) >470 msec from 3
consecutive ECGs
ii.Any clinically important abnormalities in rhythm, conduction or morphology
of resting ECG
iii.Any factors that increase the risk of QTc prolongation or risk of
arrhythmic events such as heart failure,hypokalaemia,potential for torsades de
pointes,congenital long QT syndrome,family history of long QT syndrome or
unexplained sudden death under 40 years of age,or any concomitant medication
known to prolong the QT interval
iv.Clinically significant heart disease as evidenced by myocardial infarction,
or arterial thrombotic events in the past 6 months,severe or unstable angina,or
NYHA or Class II to IV heart failure or cardiac ejection fraction measurement
of <50%
v.Experience of any of the following procedures or conditions in the preceding
6months: coronary artery bypass graft,angioplasty,vascular stent,myocardial
infarction,angina pectoris,congestive heart failure NYHA Grade >=2
vi.Uncontrolled hypotension - systolic blood pressure <90 mmHg and/or diastolic
blood pressure <50 mmHg
vii.Cardiac ejection fraction outside institutional range of normal or <50%
(whichever is higher) as measured by echocardiogram (or multiple-gated
acquisition scan if an echocardiogram cannot be performed or is inconclusive)
viii.Uncontrolled hypertension (SBP >=160 mmHg or DBP >=95 mmHg).
-Clinically significant abnormalities of glucose metabolism
-Inadequate bone marrow reserve or organ function
-As judged by the investigator, any evidence of severe or uncontrolled systemic
diseases
-Unevaluable for both bone and soft tissue progression as defined by meeting
both of the following criteria:
i.a "superscan" of bone scan,and
ii.no soft tissue lesion that can be assessed by RECIST criteria
-Previous allogeneic bone marrow transplant or solid organ transplant
-Known additional malignancy that has had progression or has required active
treatment in the last 3 years with exceptions