Table 2.
PI3K Pathway Inhibitors in Clinical Trials
| Targets | Compound (Company) | Study Population | Reported Efficacy/Responses | Reported Toxicities | References |
|---|---|---|---|---|---|
| PI3K/mTOR | SF-1126 (Semafore Pharmaceuticlas) | Phase I: advanced solid tumors | SD in 11 of 28 pts | DLT: grade 3 diarrhea (one pt) | Chiorean et al82 |
| NVP-BEZ235 (Novartis) | Phase I/II: advanced solid tumors (breast cancer-enriched) | N/A | N/A | ClinicalTrials.gov | |
| NVP-BGT226 (Novartis) | Phase I/II: advanced solid tumors (including breast cancer) | N/A | N/A | ClinicalTrials.gov | |
| XL765 (Exelixis) | Phase I: refractory solid tumors | SD in five of 36 pts | Most frequent (> 10%) AEs: elevated liver enzymes, nausea, diarrhea | LoRusso et al83 | |
| Other AEs: anorexia/hypophosphatemia, rash, vomiting, and neurologic complaints | |||||
| PI3K | PX-866 (Oncothyreon) | Phase I: advanced solid tumors | SD in two of six pts (initial dosing cohorts) | Possible AEs: abdominal discomfort, mild diarrhea | Jimeno et al84 |
| No DLTs in early dosing cohorts | |||||
| XL147 (Exelixis) | Phase I: advanced solid tumors | SD (> 6 months) in six of 39 pts; one pt with HR CaP with normalized PSA | AEs: grade 3 rash (DLT in two of three pts at highest tested dose); grade 3 arterial thrombosis (one pt); grade 2 transaminitis (one pt); grade 1 hyperglycemia (four pts) | Shapiro et al85 | |
| NVP-BKM120 (Novartis) | Phase I: solid tumors | N/A | N/A | Markman et al86 | |
| GDC-0941 (Genentech/Piramed) | Phase I: advanced solid tumors | Evidence for potential antitumor activity in three of 19 pts | Most frequent AEs: Grade 1 to 2 nausea, fatigue, diarrhea, dysgeusia, and peripheral edema | Wagner et al87 | |
| CAL-101 (Calistoga Pharmaceuticals) | Phase I: relapsed/refractory CLL or B-cell NHLs | PR in two of six pts, SD in four of six pts in early dosing cohorts | No AEs grade > 1 in first two dosing cohorts | Flinn et al88 | |
| Akt (allosteric) | MK-2206 (Merck) | Phase I: advanced solid tumors | SD in six of 19 patients | Most frequent AEs: skin (47.1%) and GI (41.2%) toxicities; DLTs: grade 3 to 4 rash, grade 3 mucositis | Tolcher et al89 |
Abbreviations: SD, stable disease; DLT, dose-limiting toxicity; Pt, patient; N/A, results from patient treatment in clinical trials have not been reported to date; AE, adverse event; HR CaP, hormone-refractory prostate cancer; PSA, prostate-specific antigen; CLL, chronic lymphocytic leukemia; NHL, non-Hodgkin's lymphoma; PR, partial response.