Table 3.
List of the main clinical trials currently active involving drugs targeting the PI3K/AKT/mTOR pathway in advanced triple-negative breast cancer
| Trial identifier | Phase | Patient population | Biomarker for PI3K/AKT/mTOR pathway activation | Drug | Molecular target/Drug class |
|---|---|---|---|---|---|
| NCT04251533 (EPIK-B3) | Phase 3 | Advanced TNBC | PIK3CA mutation or PTEN loss | Alpelisib + Nab-paclitaxel vs Placebo + Nab-paclitaxel | PI3K-α inhibitor + chemotherapy |
| NCT03961698 (MARIO-3) | Phase 2 | Advanced TNBC | None | Eganelisib (IPI-549) + Atezolizumab + Nab-paclitaxel | PI3K-γ inhibitor + immune checkpoint inhibitor + chemotherapy |
| NCT03911973 | Phase 2 | Advanced TNBC or BRCA1/2-mutated HER2-negative BC | None | Gedatolisib + Talazoparib | PI3K and mTOR inhibitor + PARP inhibitor |
| NCT02531932 | Phase 2 | Advanced TNBC | None | Carboplatin + Everolimus vs Carboplatin + Placebo | mTOR inhibitor + chemotherapy |
| NCT03193853 | Phase 2 | Advanced TNBC | None | Serabelisib (TAK-117) + Sapanisertib (TAK-228) + Cisplatin + Nab-paclitaxel | PI3K-α inhibitor + mTORC1/2 inhibitor + chemotherapy |
| NCT03801369 | Phase 2 | Advanced TNBC | None | Olaparib + Capivasertib (AZD5363) or Olaparib + Durvalumab or Olaparib + Selumetinib (AZD6244) or Ceralasertib (AZD6738) | PARP inhibitor + AKT inhibitor or PARP inhibitor + immune checkpoint inhibitor or MEK inhibitor + PARP inhibitor or ATR inhibitor |
| NCT02208375 | Phase 1b/2 | Advanced TNBC and gynecological malignancies | None | Olaparib + Vistusertib (AZD2014) or Olaparib + Capivasertib (AZD5363) | mTORC1/2 inhibitor + PARP inhibitor or AKT inhibitor + PARP inhibitor |
| NCT02457910 | Phase 1b/2 | Advanced TNBC androgen receptor positive | None | Taselisib + Enzalutamide | PI3K inhibitor + Androgen receptor inhibitor |
| NCT03805399 (FUTURE) | Phase 1b/2 | Advanced TNBC further classified in four subtypes (LAR, IM, BLIS, MES) | LAR subtype without ERBB2 mutation and with PIK3CA mutation, MES subtype with PIK3CA mutation | Everolimus + SHR3680 (Arm B1) or Everolimus + Nab-paclitaxel (Arm G) or other arms | mTOR inhibitor + Androgen receptor inhibitor or mTOR inhibitor + chemotherapy |
| NCT04395989 (FUTURE SUPER) | Phase 2, Umbrella trial | Advanced TNBC further classified in four subtypes (LAR, IM, BLIS, MES) | LAR subtype without ERBB2 mutation and with PI3K/AKT/mTOR pathway mutation, MES subtype with PI3K/AKT/mTOR pathway mutation | Everolimus + Nab-paclitaxel (Arms B1 and E1) or other arms | mTOR inhibitor + chemotherapy |
| NCT03742102 (BEGONIA) | Phase 1b/2 | Advanced TNBC | None | Capivasertib (AZD5363) + Durvalumab + Paclitaxel or other arms | AKT inhibitor + immune checkpoint inhibitor + chemotherapy |
| NCT02583542 | Phase 1b/2a | TNBC and lung cancer | None | AZD2014 + Selumetinib (AZD6244) | mTORC1/2 inhibitor + MEK inhibitor |
| NCT03207529 | Phase 1b | Advanced HR + BC or TNBC androgen receptor–positive and PTEN-positive (on IHC) | PTEN nuclear staining >0% in IHC | Alpelisib + Enzalutamide | PI3K-α inhibitor + Androgen receptor inhibitor |
| NCT02637531 | Phase 1/1b | Advanced solid tumors, among which TNBC | None | Eganelisib (IPI-549) + Nivolumab | PI3K-γ inhibitor + immune checkpoint inhibitor |
| NCT03218826 | Phase 1 | Advanced solid tumors, among which HER2-negative BC and TNBC | PTEN loss of function mutation or PIK3CB gain of function mutation | AZD8186 + Docetaxel | PI3K-β inhibitor + chemotherapy |
(TNBC) Triple-negative breast cancer, (BC) breast cancer, (LAR) luminal androgen receptor, (IM) immunomodulatory, (BLIS) basal-like immune suppressed, (MES) mesenchymal, (HR) hormone receptor, (IHC) immunohistochemistry.