A study evaluating the safety, preliminary efficacy and pharmacokinetics of ipatasertib in
combination with atezolizumab and docetaxel in participants with mCRPC previously treated
with second-generation AR (Androgen Receptor)-targeted therapy. The study consists of two
parts:  Part A: Safety run-in cohort of approximately 12 participants;  Part B:
Expansion cohort of approximately 38 participants. All participants in this study will
continue to be treated until progression of disease, loss of clinical benefit, unacceptable
toxicity or withdrawal of consent.
- Ability to comply with the study protocol.
- Adenocarcinoma of the prostate without small-cell or neuroendocrine features.
- Metastatic disease that cannot be treated with curative intent.
- Surgical or medical castration with testosterone serum level < 50 ng/dL (1.7 nM).
- For participants treated with luteinizing hormone-releasing hormone analogs,
initiation therapy >= 4 weeks prior to the first dose of study treatment and continued
therapy throughout study treatment.
- Progression of Prostate Cancer.
- Receipt of at least one prior line of second generation AR-targeted therapy.
- For participants in Part A of study: measurable visceral disease or measurable
extrapelvic adenopathy per RECIST v1.1.
- For participants in Part B of study: either measurable visceral disease or measurable
extrapelvic adenopathy by RECIST v1.1 or bone lesions by bone scan, or both.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Life expectancy of >= 3 months.
- Ability to swallow oral study drug.
- Adequate organ and bone marrow function.
- Resolved or stabilized toxicities resulting from previous therapy to Grade 1 (except
for alopecia and neuropathy).
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm.
- Prior treatment with an AKT, PI3K, or mTOR inhibitor.
- Prior treatment with radium or other therapeutic radiopharmaceuticals for prostate
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40,
- Prior treatment with docetaxel or another chemotherapy agent for mCRPC.
- Treatment with investigational therapy within 14 days prior to initiation of study
- History or known presence of central nervous system metastases including
- Uncontrolled tumor-related pain.
- Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement)
amenable to palliative radiotherapy should be treated prior to enrollment.
- Asymptomatic metastatic lesions whose further growth would likely cause functional
deficits or intractable pain (e.g., epidural metastasis that is not presently
associated with spinal cord compression) should be considered for loco- regional
therapy if appropriate prior to enrollment.
- Non-study-related minor surgical procedures =< 5 days or major (invasive) surgical
procedure =< 28 days prior to the first dose of study treatment.
- Active Hepatitis B and C infection (HBV/HCV).
- Known HIV infection.
- Uncontrolled pleural effusion, pericardial effusion, or ascites.
- Illicit drug or alcohol abuse within 12 months prior to screening, in the
- Malabsorption syndrome or other condition that would interfere with enteral
- Serious infection requiring antibiotics within 14 days prior to the first dose of
- Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator's judgment, precludes the participant's safe participation in and
completion of the study.
- History of another malignancy within 5 years prior to enrollment.
- History of clinically significant cardiovascular dysfunction.
- Presence of any other condition, metabolic dysfunction, physical examination finding,
or laboratory finding that may increase the risk associated with study participation
or may interfere with the interpretation of study results and in the opinion of the
investigator, would make the participant inappropriate for study entry.
Ipatasertib-Specific Exclusion Criteria:
- Type 1 or Type 2 diabetes mellitus requiring insulin at study entry.
- History of inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis) or
active bowel inflammation (e.g., diverticulitis).
- Grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
- Treatment with strong CYP3A inhibitor or strong CYP3A inducer within 2 weeks or 5
drug-elimination half-lives of this treatment (whichever is longer) prior to
initiation of study drug.
Atezolizumab-Specific Exclusion Criteria:
- Active or history of autoimmune disease or immune deficiency.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest computed tomography (CT) scan.
- Prior allogeneic stem cell or solid organ transplantation.
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
treatment, or anticipation of need for such a vaccine during treatment with
atezolizumab or within 5 months after the last dose of atezolizumab.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
or fusion proteins.
- Known hypersensitivity to Chinese hamster ovary cell products or recombinant human
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination
half-lives of the drug (whichever is longer) prior to initiation of study treatment.
- Need for chronic corticosteroid therapy of >10 mg of prednisone per day or an
equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a
- Treatment with systemic immunosuppressive medication within 2 weeks prior to
initiation of study treatment, or anticipation of need for systemic immunosuppressive
medication during the course of the study.
Docetaxel-Specific Exclusion Criteria:
- Known hypersensitivity or contraindication to any component of docetaxel, including
its excipient polysorbate 80.
- Grade >= 2 peripheral neuropathy.