Table 1.
Ongoing clinical trials of therapies targeting PD-L1 expression regulation, in combination with immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC): (source: www.clinicaltrials.gov, last accessed: 9 September 2020).
| NCT | Phase | Experimental Agent | Tumor | Setting | N | Arm(s) | Primary Outcome(s) |
|---|---|---|---|---|---|---|---|
| PI3K Inhibitor | |||||||
| NCT02637531 | I | IPI-549 | AST | After standard | 219 | IPI-549 ± Nivolumab | AEs DLT |
| NCT03257722 | Ib/II | Idelalisib | NSCLC | Progressed on chemotherapy and ICIs | 40 | Idelalisib + Pembrolizumab | DLT |
| NCT04282018 | I/II | BGB-10188 | AST | After standard | 150 | BGB-10188 + Tislelizumab | AEs |
| mTOR Inhibitor | |||||||
| NCT04348292 | I | Sirolimus | Stage I-IIIA NSCLC | Neoadjuvant | 31 | Sirolimus + Durvalumab | AEs CPRR |
| NCT03190174 | I/II | ABI-009 (Nab-rapamycin) |
AST | Any line | 40 | ABI-009 + Nivolumab | MTD |
| JAK1 Inhibitor | |||||||
| NCT03425006 | II | Itactinib | NSCLC | 1st line | 48 | Itactinib + Pembrolizumab | ORR AEs |
| PARP Inhibitor | |||||||
| NCT03330405 | Ib/II | Talazoparib | AST | BRCA or ATM deficient | 214 | Talazoparib + Avelumab | DLT ORR |
| NCT03559049 | I/II | Rucaparib | NSCLC | Maintenance after 1st line immuno-chemotherapy | 55 | Pembrolizumab + Rucaparib | PFS |
| NCT04538378 | II | Olaparib | EGFR-mutated NSCLC transformed to SCLC | After platinum-based chemotherapy ± immunotherapy for SCLC trasformation | 14 | Olaparib + Durvalumab | BOR |
| NCT03775486 | II | Olaparib | NSCLC | Maintenance after 1st line chemotherapy | 401 | Olaparib ± Durvalumab | PFS |
| NCT03308942 | II | Niraparib | NSCLC | 1st line | 53 | Niraparib ± Pembrolizumab/Dostarlimab | ORR |
| NCT04380636 | III | Olaparib | Stage III NSCLC | Unresectable | 870 | Pembrolizumab + chemoradiation→ Pembrolizumab ± OlaparibChemoradiation→Durvalumab | PFS OS |
| NCT03976323 | III | Olaparib | NSCLC | Maintenance after 1st line immuno-chemotherapy | 792 | Pembrolizumab + Olaparib Pembrolizumab + Pemetrexed |
PFS OS |
| NCT03976362 | III | Olaparib | NSCLC | Maintenance after 1st line immuno-chemotherapy (CBDCA + taxane) | 735 | Pembrolizumab ± Olaparib | PFS OS |
| ATR Inhibitor | |||||||
| NCT03334617 | II | AZD6738 | NSCLC | ≥2nd line | 340 | Durvalumab + AZD6738 | ORR |
| NCT03833440 | II | AZD6738 | NSCLC | 3rd - 4th line (after ICI) | 120 | Durvalumab + AZD6738 | DCR at 12 weeks |
| TGFBR1 Inhibitor | |||||||
| NCT03732274 | I/II | Vactosertib (TEW-7197) |
NSCLC | After chemotherapy | 63 | Vactosertib + Durvalumab | MTD |
| Epigenetic Drugs | |||||||
| NCT02437136 | I/II | Entinostat | NSCLC, melanoma, mismatch repair-proficient CRC | ≥2nd line | 202 | Entinostat + Pembrolizumab | AEs ORR |
| NCT01928576 | II | Azacytidine | NSCLC | Any line | 120 | Azacitidine + Entinostat + Nivolumab | ORR |
| NCT02546986 | II | Azacytidine | NSCLC | 2nd line | 100 | Pembrolizumab ± Azacitidine | PFS |
| NCT04250246 | II | Guadecitabine | NSCLC Melanoma |
≥2nd line (only one prior line of ICIs allowed) |
184 | Ipilimumab + Nivolumab ± Guadecitabine | ORR |
N: planned sample size; NCT: clinicaltrials.gov identifier; AEs: adverse events; AST: advanced solid tumors; BOR: best overall response; CPRR: complete pathological response rate; CRC: colorectal cancer; DCR: disease control rate; DLT: dose-limiting toxicities; MTD: maximum tolerated dose; NSCLC: non-small-cell lung cancer; ORR: objective response rate; OS: overall survival; PFS: progression-free survival.