Table 1.
PI3K and AKT inhibitor agents in clinical development.
| Agent | Pharmaceutical Company | Sponsor | Trial | Endpoint | Patient Population | Status | Biomarkers |
|---|---|---|---|---|---|---|---|
| BKM120 (PI3K) | Novartis | Duke University | Phase II, BKM120 in mCRPC (NCT01385293) |
PFS | Post chemo; prior sipuleucel-T, abiraterone (Abi), or enzalutamide (enza) allowed. n = 66 |
Study accrued, results awaited | Circulating tumor cells (CTCs), Tissue PI3K signature, PTEN status, PI3K activation, PSA levels |
| University of California | Phase II, neoadjuvant BKM120 for high-risk prostate cancer pre radical prostatectomy (RP) (NCT01695473) | PI3K inhibition in tumor measured by IHC | Candidates for RP; high risk defined by trial Target n = 24 |
Study accrued, results awaited | IHC for phosphorylation of: S6, 4EBP1, or AKT | ||
| GSK2636771 (PI3K) | GlaxoSmithKline | GSK | Phase I, GSK2636771 in combination with Enza for mCRPC (NCT02215096) |
Safety and tolerability | PTEN deficient tumors post progression on Enza n = 44 | Recruiting | PTEN status PSA levels |
| AZD8186 (PI3K) | AstraZeneca | AZ | Phase I, AZD8186 +/− Abi or AZD2014 in TNBC/NSCLC or CRPC or known PTEN-deficient/PI3 mutated disease (NCT01884285) | Safety and tolerability | mCRPC (Total) Target n = 180 |
Recruiting | PSA levels |
| LY3023414 (PI3K + mTOR) | Eli Lilly | Eli Lilly | Phase II Study of Enzalutamide +/− LY3023414 in mCRPC (NCT02407054) | PFS | mCRPC post progression on Abi; no prior chemo in castrate-refractory setting, immunotherapy, or Ra223 Target n = 144 |
Recruiting | PSA levels |
| AZD5363 (AKT) | AstraZenica | Institute of Cancer Research, UK | Phase I/II, Enza +/− AZD5363 in mCRPC | Phase II: Best overall tumor response | mCRPC with tissue for PTEN testing Target n = 136 |
Recruiting | PTEN PSA levels |
| University Hospital Southampton NHS Foundation Trust | Randomised Phase II, Docetaxel +/− AZD 5363 in mCRPC | PFS | Chemotherapy-naïve mCRPC | Recruiting | PSA levels | ||
| MK2206 (AKT) | Merck | National Cancer Institute | Phase II, bicalutamide +/− MK2206 in men with HSPC | Proportion undetectable PSA | Biochemically relapsed hormone-sensitive PC following definitive treatment n = 104 |
Study accrued, results awaited | PSA levels |