Table 1.
Clinical trials of PI3K/AKT/mTOR inhibitors in HER2-positive and triple negative breast cancer.
| PI3K Inhibitor | Combined Treatment | Mutation on PI3K/Akt/mTOR Pathway Related Genes Required | Phase | Setting | NCT Number/Study Name |
|---|---|---|---|---|---|
| Alpelisib α | +Trastuzumab + pertuzumab | Yes, in part 2 | III | Advanced HER2+ BC following induction with taxane | NCT04208178 |
| (EPIK-B2) | |||||
| Copanlisib ∞ | Trastuzumab + pertuzumab | Yes | I/II | Advanced HER2+ BC following induction with taxane | NCT04108858 |
| Taselisib β | Arm A: Taselisib with T-DM1 | No | I | mBC, HER2+ | NCT02390427 |
| Arm B: Taselisib with T-DM1 and pertuzumab | |||||
| Arm C: Taselisib with pertuzumab and trastuzumab | |||||
| Arm D: Taselisib with pertuzumab, trastuzumab and paclitaxel | |||||
| Copanlisib ∞ | Trastuzumab | No | I/II | mBC, HER2+ | NCT02705859 |
| ≥1 line with Trastuzumab or T-DM1 | (Panther) | ||||
| BEZ235 (Dactolisib) ¥ | + Trastuzumab | No | I/II | mBC, HER2+ after Trastuzumab | NCT01471847 |
| GDC-0084 × | + Trastuzumab | No | II | mBC, HER2+ | NCT03765983 |
| with brain mets | |||||
| MEN1611 * | Trastuzumab +/− fulvestrant (if HR+) | Yes | I | mBC, HER2+, | NCT03767335 (B-PRECISE-01) |
| >2 lines of anti-HER2 | |||||
| MK2206 γ | Trastuzumab and Lapatinib | No | I | Advanced HER2+ BC | NCT01705340 |
| MK2206 γ | Lapatinib | No | I | Advanced HER2+ BC | NCT01245205 |
| Ipatasertib γ | Trastuzumab + Pertuzumab + ET (if HR+) | Yes | I | Advanced HER2+ BC | NCT04253561 |
| Inavolisib α | Pertuzumab + Trastuzumab + Hyaluronidase + ET | Yes | II | Neoadjuvant HER2+, HR+ BC | NCT05306041 |
| (GeparPiPPa) | |||||
| Alpelisib α | Trastuzumab (+ET) vs chemotherapy + trastuzumab |
Yes | III | mBC, HER2+/HR+ | NCT05063786 |
| 1 < line < 5 | (ALPHABET) | ||||
| Alpelisib α | T-DM1 | No | I | mBC, HER2+ after Trastuzumab-taxane regimen | NCT02038010 |
| Alpelisib α | + trastuzumab + pertuzumab + chemotherapy | Yes | I | Neoadjuvant HER2+ BC | NCT04215003 |
| XL147 (SAR245408, Pilaralisib) i | Trastuzumab (+/- paclitaxel) | No | I/II | mBC, HER2+ after Trastuzumab | NCT01042925 |
| Alpelisib α | Tucatinib + fulvestrant | Yes | I/II | Advacnced BC, HER2+, >2 lines | NCT05230810 |
| BKM120 (Buparlisib) i | Lapatinib | Yes | I/II | Trastuzumab-resistant | NCT01589861 (PIKHER2) |
| mBC, HER2+ | |||||
| BKM120 (Buparlisib) i | Trastuzumab + Paclitaxel | No | I II | Neoadjuvant HER2+ | NCT01816594 (NeoPHOEBE) |
| Rapamycin | Inetetamab + chemotherapy vs. pyrotenib + chemotherapy |
Yes | III | mBC, HER2+ after Trastuzumab | NCT04736589 |
| Taselisibβ/Pictilisib i | Palbociclib | Yes | I | mBC, HER2+ >2 lines | NCT02389842 |
| mTNBC >1 line | |||||
| AZD5363 (Capivasertib) γ | / | Yes | I | mBC, ER+/HER2+ | NCT01226316 |
| Everolimus | Nab-paclitaxel | Yes | II | mTNBC | NCT04395989 |
| Alpelisib α | Nab-Paclitaxel | Yes or loss of function PTEN | II | Anthracycline refractory-TNBC, neoadjuvant | NCT04216472 |
| Alpelisib α | Sacituzumab govitecan | No | I | Advanced TNBC | NCT05143229 |
| Alpelisib α | Nab-paclitaxel | Yes or loss of function PTEN | III | Advanced TNBC, 2nd line | NCT04251533 (EPIK-B3) |
| Inavolisib α | / | Yes | I | mTNBC | NCT03006172 |
| CUDC907 (Fimepinostat) ç | / | No | I | mTNBC | NCT02307240 |
| Alpelisib α | Enzalutamide | AR-positive and PTEN-positive | I | mTNBC | NCT03207529 |
| Copanlisib ∞ | Eribulin | No | I/II | Advanced TNBC, | NCT04345913 |
| 1 < line ≤ 5 | |||||
| PF-05212384 (Gedatolisib) # | PTK-ADC | No | I | mTNBC, | NCT03243331 |
| ≥2nd line | |||||
| Taselisib β | / | Yes, without KRAS mutations or PTEN Loss | I | mTNBC | NCT04439175 |
| INCB050465 (Parsaclisib) ‡ | Pembrolizumab | No | I | mTNBC | NCT02646748 |
| PQR309 (Bimiralisib) ¥ | Eribulin | No | I | Advanced TNBC | NCT02723877 (PIQHASSO) |
| 1 < line ≤ 5 | |||||
| Everolimus | Anti-PD1 | No | I | mTNBC | NCT02890069 |
| AZD5363 (Capivasertib) γ | Paclitaxel | No | II | mTNBC | NCT02423603 |
| AZD2014 (Vistusertib) < | Selumetinib | Yes, or Ras/MEK pathway | II | mTNBC | NCT02583542 |
| Taselisib β | Enzalutamide | No | I/II | mTNBC, AR+ | NCT02457910 |
| Everolimus | AR-inhibitor | Yes and LAR subtype | I/II | mTNBC | NCT03805399 |
| Alpelisib α | / | Yes | II | mTNBC, ≥2nd line | NCT02506556 (PIKNIC) |
| Tenalisib ¤ | / | No | II | mTNBC | NCT05021900 |
| Ipatasertib γ | Paclitaxel vs. placebo + paclitaxel | Yes | III | mTNBC, 1st line | NCT03337724 |
| BKM120 (Buparlisib) i or Alpelisib α | Olaparib | No | I | mTNBC, >1st line | NCT01623349 |
| PF-05212384 (Gedatolisib) # | PTK7-ADC | No | I | mTNBC, >1st line | NCT03243331 |
| Ipatasertib γ | + paclitaxel +/-atezolizumab | No | III | mTNBC | NCT04177108 |
| Eganelisib ¶ | Atezolizumab + nab-paclitaxel | No | II | mTNBC, 1st line | NCT03961698 (MARIO-3) |
| Eganelisib ¶ | Nivolumab | No | I | mTNBC | NCT02637531 |
| AZD8186 † | / | No | I | mTNBC | NCT01884285 |
| AZD8186 † | Docetaxel | Yes or loss of function PTEN | I | Advanced BC | NCT03218826 |
| Ipatasertib γ | / | Yes | II | mBC, ≤2 lines | NCT04591431 |
| LOXO-783 § | Alone or + paclitaxel | Yes, PIK3CA H1047R mutation | I | mBC, <5 lines | NCT05307705 |
| AZD8835 ∞ | / | Yes | I | mBC | NCT02260661 |
| Taselisib β/ Capivasertib γ/ Copanlisib ∞ |
/ | Yes, PIK3CA or AKT | I | mBC | NCT02465060 |
| MK2206 γ | Paclitaxel | No | I | mBC, ≤3 lines | NCT01263145 |
| Alpelisib α | / | Yes | I | mBC | NCT05238831 |
| Inavolisib α | / | Yes | II | mBC | NCT05332561 |
| BEZ235 (Dactolisib) ¥ | MEK162 | No | I | mBC | NCT01337765 |
| CYH33 α | Olaparib | Yes or on DDR gene | I | mBC | NCT04586335 |
| PF-05212384 (Gedatolisib) # | Paclitaxel and carboplatin | No | I | mBC | NCT02069158 |
| RLY-2608 α | / | Yes | I | Advanced solid tumors | NCT05216432 |
| Alpelisib α | / | Yes | I | Solid tumors | NCT01219699 |
* PI3K α/β/γ inhibitor; γ AKT inhibitor; ∞ PI3K α/δ inhibitor; β PI3K α/δ/γ inhibitor; i PI3K α/β/δ/γ inhibitor; × PI3Kα and mTOR inhibitor, α PI3Kα inhibitor; ¥ PI3K α/β/δ/γ and mTOR inhibitor; † PI3K β/δ inhibitor; ç PI3K and HDAC (histone deacetylases) inhibitor; ‡ PI3Kδ inhibitor; ¤ PI3Kδ/γ inhibitor; ¶ PI3Kγ inhibitor; § PI3Kα H1047R inhibitor; # PI3Kα/γ and mTOR inhibitor; < pan mTOR inhibitor. Abbreviations: ET, endocrine therapy; HR, hormone receptor; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer; BC, breast cancer; T-DM1, Trastuzumab emtansine; mBC, metastatic breast cancer; AR, androgen receptor; mTNBC, metastatic triple negative breast cancer; DDR, DNA damage repair.