Table 1.
Ongoing clinical trials with PI3K/AKT/mTOR inhibitors in HNSCC.
| Class | Drug | Patient Cohort | Biomarker | Phase | Clinical Trials | Intervention | Status |
|---|---|---|---|---|---|---|---|
| Pan-PI3K inhibitor | Buparlisib (BKM-120) | R/M HNSCC | None | III | NCT04338399 | Buparlisib + paclitaxel | Recruiting |
| LA-HNSCC | HPV-positive | I | NCT02113878 | Buparlisib with cisplatin + IMRT | Completed, Awaiting results | ||
| Copanlisib (BAY 80-6946) | R/M HNSCC | None | I | NCT03735628 | Copanlisib + nivolumab | Active, not recruiting | |
| R/M HNSCC | PIK3CA mutation, PTEN mutation/loss | II | NCT02465060 | Copanlisib | Recruiting | ||
| Isoform-specific PI3K inhibitor | Alpelisib (BYL-719) (PI3Kα) | LA-HNSCC | HPV-positive | II | NCT03601507 | Alpelisib | Recruiting |
| R/M HNSCC | HRAS overexpression, PIK3CA mutation and/or amplification | I/II | NCT04997902 | Tipifarnib + alpelisib | Recruiting | ||
| R/M HNSCC | PI3K pathway alterations | II | NCT03292250 | Alpelisib | Completed, awaiting results | ||
| R/M HNSCC | None | II | NCT02145312 | Alpelisib | Unknown | ||
| R/M HNSCC | None | I | NCT01822613 | Alpelisib + LJM716 | Completed, awaiting results | ||
| LA-HNSCC | None | I | NCT02282371 | Alpelisib with cetuximab + IMRT | Completed, awaiting results | ||
| LA-HNSCC | None | I | NCT02537223 | Alpelisib with cisplatin + IMRT | Completed, awaiting results | ||
| Duvelisib (VS-0145) (PI3K δ/γ) | R/M HNSCC | None | II | NCT05057247 | Duvelisib + docetaxel | Recruiting | |
| GSK2636771 (PI3K β) | R/M HNSCC | PTEN mutation/loss | II | NCT02465060 | GSK2636771 | Recruiting | |
| Parsaclisib (INCB050465) (PI3K β) | R/M HNSCC | None | I | NCT02646748 | Parsaclisib + pembrolizumab | Completed, awaiting results | |
| Serabelisib (INK-117) (PI3K α) | LA-HNSCC | PIK3CA mutation, KRAS mutation | I/II | NCT04073680 | Serabelisib + canagliflozin | Unknown | |
| Taselisib (GDC-0032) (PI3K α/δ/γ) | R/M HNSCC | PIK3CA mutation, PTEN mutation/loss | II | NCT02465060 | Taselisib | Recruiting | |
| Dual PI3K/mTOR inhibitor | Gedatolisib (PF-05212384) | R/M HNSCC | PI3K pathway alterations | I | NCT03065062 | Gedatolisib + palbociclib | Recruiting |
| AKT inhibitor | Ipatasertib (GDC-0068) | R/M HNSCC | AKT mutation | II | NCT02465060 | Ipatasertib | Recruiting |
| LA-HNSCC | None | I | NCT05172245 | Ipatasertib with cisplatin + RT | Recruiting | ||
| R/M HNSCC | None | II | NCT05172258 | Ipatasertib + pembrolizumab | Recruiting | ||
| Capivasertib (AZD5363) | R/M HNSCC | AKT mutation | II | NCT02465060 | Capivasertib | Recruiting |
AKT = AKT kinase; HPV = human papillomavirus; IMRT = intensity-modulated radiation therapy; mTOR = mammalian target of rapamycin; PI3K = phosphoinositide 3-kinase; LA-HNSCC = locally advanced head and neck squamous cell carcinoma; R/M HNSCC = recurrent and metastatic head and neck squamous cell carcinoma.