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Table 3 Summary of clinical activity of phosphatidylinositol 3-kinase (PI3K) inhibitors in phase I clinical trials

From: Clinical development of phosphatidylinositol 3-kinase inhibitors for cancer treatment

Agent/dose N Selected Tumor type with PR (RECIST) Molecular profile status References
Pan-isoform PI3K inhibitors
SAR245408 (XL147) 75 No NSCLC No alteration [6]
BKM120 66 No (expansion only) TN breast KRAS mutation [7]
    ER+ HER2- breast PIK3CA mutation  
    Parotid cancer PIK3CA mutation  
GDC-0941      
Once a day 42 No Melanoma BRAF V600E mutation [8]
Once a day or twice a day 97 No ER+, HER2- breast Unknown [9]
    Endocervical adenocarcinoma PIK3CA mutation  
BAY 80-9646      
Dose escalation 17 No None - [10]
Expansion: solid 30 No ER+ HER2- Breast No alteration [11]
    ER+ HER2+ Breast HER2 amplification  
Expansion: NHL 5 No Follicular lymphoma (5 patients) No alteration (0 of 5 patients) [11]
CH5132799 31 No None -a [12]
PX-866 84b No None - [13]
Pan-isoform PI3K-mTOR inhibitors      
SAR245409 (XL765)      
Solid tumors 83 No None - [14]
Lymphoma 16 No Mantle cell lymphoma Unknown [15]
    Transformed lymphoma Unknown  
    Diffuse large B-cell lymphoma Unknown  
BEZ235      
Once a day 59c No (expansion only) ER+ HER2- breast Unknown [16]
    NSCLC PTEN mutation (Cowden)  
Twice a day 16 No None - [17]
GSK2126458 129 No (expansion only) Renal No alteration [18]
    Renal PTEN loss  
    Bladder PIK3CA mutation  
    Bladder Unknown  
GDC-0980 42 No Adrenal cortical Unknown [19]
  32 No None - [20]
SF-1126 39 No None - [21]
PF-04691502 33 No None - [22]
PF-05212384 53 No (expansion only) Ovarian cancer No alteration [23]
    NSCLC EGFR mutation  
BGT-226 57 No None - [24]
PI3Kα-specific inhibitors
BYL719 35 Yes ER+ breast PIK3CA mutation [25]
    Cervix PIK3CA mutation  
    Colon PIK3CA and KRAS mutations  
PI3Kδ-specific inhibitors      
GS-1101      
CLL 54 No 26% RR according to IWCLL Unknown [26]
Non-Hodgkin's lymphoma 49 No Indolent NHL (15 PR out of 24); mantle cell lymphoma (10 PR out of 16) Unknown [27]
  1. aPatient with ovarian cancer, with PIK3CA mutation still receiving treatment, with -17.2% reduction of target lesions and 75% decrease in CA-125.
  2. bA total of 56 patients evaluable for response.
  3. cA total of 51 patients evaluable for response.
  4. BRAF = v-raf murine sarcoma viral oncogene homolog B1; CA = cancer antigen; CLL = chronic lymphocytic leukemia; EGFR = epidermal growth factor receptor; ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; IWCLL = International Workshop on Chronic Lymphocytic Leukemia; KRAS = v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; mTOR = mammalian target of rapamycin; NHL = non-Hodgkin's lymphoma; NSCLC = non-small cell lung cancer; PIK3CA = phosphatidylinositol 3-kinase p110α isoform gene; PR = partial response; RECIST = Response Evaluation Criteria In Solid Tumors; RR = response rate; TN = triple negative.