Table 1.
Ongoing clinical trials of non–HER2-targeted agents in development for the treatment of HER2-resistant advanced breast cancer
| Developmental agent | Design and study treatment | ClinicalTrials.gov identifier |
|---|---|---|
| IGF1R inhibitors | ||
| BMS-754807 | Open-label, phase I/II | NCT00788333 |
| Trastuzumab + BMS-754807 | ||
| Cixutumumab | Randomized, placebo-controlled, phase II | NCT00684983 |
| Lapatinib + capecitabine ± cixutumumab | ||
| OSI-906 | Open-label, phase II | NCT01205685 |
| Erlotinib + letrozole + OSI-906 | ||
| HSP90 inhibitor | ||
| AUY922 | Open-label, phase Ib/II | NCT01271920 |
| Trastuzumab + AUY922 | ||
| Open-label, phase I/II | NCT01361945 | |
| Lapatinib + letrozole + AUY922 | ||
| Ganetespib | Open-label, phase I | NCT01273896 |
| Ganetespib monotherapy | ||
| Telomerase inhibitor | ||
| GRN163L | Open-label, phase I | NCT01265927 |
| Trastuzumab + GRN163L | ||
| PI3K inhibitors | ||
| BKM120 | Open-label, phase I/II | NCT01132664 |
| Trastuzumab + BKM120 | ||
| GDC-0941 | Open-label, phase I | NCT00928330 |
| Trastuzumab or T-DM1 + GDC-0941 | ||
| XL147 | Trastuzumab + XL147 ± paclitaxel | NCT01042925 |
| Open-label, phase I/II | ||
| Akt inhibitor | ||
| MK2206 | Open-label, phase I | NCT01245205 |
| Lapatinib + MK2206 | ||
| Open-label, phase II | NCT01277757 | |
| MK2206 monotherapy | ||
| mTOR inhibitors | ||
| Temsirolimus | Open-label, phase I-II | NCT01111825 |
| Neratinib + temsirolimus | ||
| Everolimus | Open-label, phase II | NCT01305941 |
| Vinorelbine + trastuzumab + everolimus | ||
| Open-label, phase II | NCT01283789 | |
| Lapatinib + everolimus | ||
| Randomized, placebo-controlled, phase III | NCT01007942 | |
| Vinorelbine + trastuzumab ± everolimus | ||
| INK128 | Open-label, phase I | NCT01351350 |
| Paclitaxel + trastuzumab + INK128 | ||
| Dual PI3K/mTOR inhibitor | ||
| BEZ235 | Open-label, phase I/Ib | NCT00620594 |
| Trastuzumab + BEZ235 | ||
| Open-label, phase Ib, randomized phase II | NCT01471847 | |
| Trastuzumab + BEZ235 (versus lapatinib + capecitabine in phase II) | ||
NB: Not all trials are limited to patients with HER2-positive breast cancer that progressed after HER2-targeted therapy.
HSP90, heat shock protein 90; IGF1R, insulin-like growth factor receptor 1; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase.