Table 7.
Ongoing clinical trials of molecular-targeted agents in NEC
| Trials | Targets | Agents | Line | Phase | Primary sites | Treatment |
|---|---|---|---|---|---|---|
| mTOR inhibitors | ||||||
| NCT02113800 | mTOR | Everolimus (Eve) | 2nd | II | Any | Mono |
| NCT02687958 | 1st | II | GEP (Ki-67 < 55%) | Mono | ||
| NCT02248012 | 1st | II | GEP or UK (Ki-67 < 55%) | Eve + TEM | ||
| NCT02695459 | 1st | II | Any | Eve + CDDP | ||
| Anti-angiogenetic inhibitors | ||||||
| NCT04705519 | VEGF-A | Bevacizumab (Bev) | 2nd | II | Any | Bev + nab-PTX |
| NCT03457844 | VEGFR | Anlotinib (Anlo) | 2nd | II | Any | Mono |
| NCT05165407 | Surufatinib (Sur) | 2nd | II | Any | Sur + Sin + IBI310 | |
| NCT05015621 | 2nd | III | Any | Sur + Tori vs. FOLFIRI | ||
| NCT04412629 | Cabozantinib (Cab) | 2nd | II | GEP | Mono | |
| NCT04400474 | Any | II | Any | Cab + Atezo | ||
| NCT04079712 | 2nd | II | Any | Cab + Nivo + Ipi | ||
| Inhibitors of cell-cycle or DDR regulators | ||||||
| NCT04514497 | ATR | Elimusertib (Elimu) | 2nd | II | Any | Elimu + CPT-11/TPT |
| NCT04802174 | Berzosertib (Berzo) | 2nd | I/II | Any | Berzo + Lurbinectedin | |
| NCT02487095 | 1st | II | Any (only SCNEC) | Berzo + TPT | ||
| NCT03896503 | 1st | II | Any (only SCNEC) | TPT ± Berzo | ||
| NCT04209595 | PARP | Rucaparib (Ruca) | 2nd | I/II | Any (only SCNEC) | Ruca + PLX038 |
| NCT04701307 | Niraparib (Nira) | 2nd | II | Any | Nira + Dostarlimab | |
| Inhibitors of epigenetic regulators | ||||||
| NCT05076786 | HDAC | Tucidinostat (Tuci) | 1st | II | Extrapulmonary | Tuci + CDDP/CBDCA + ETP |
| NCT05113355 | 2nd | II | Any | Tuci + Sin | ||
| Immune checkpoint inhibitors | ||||||
| NCT03147404 | PD-L1 | Avelumab | 2nd | II | GEP | Mono |
| NCT05058651 | Atezolizumab (Atezo) | 1st | II/III | Any | CDDP/CBDCA + ETP ± Atezo | |
| NCT05142865 | PD-1 | Camrelizumab (Camre) | 1st | II | Extrapulmonary | Camre + CDDP/CBDCA + ETP + Apatinib |
| NCT03992911 | Toripalimab (Tori) | 1st | II/III | Any | Tori + Simmtecan + 5-FU/LV vs. CDDP/CBDCA + ETP | |
| NCT03517488 | PD-1/CTLA-4 | XmAb20717 | 2nd | I | Any | Mono |
| NCT05337735 | 2nd | II | Any | Mono | ||
| DLL3 targeting agents | ||||||
| NCT04429087 | DLL3/CD3 | BI 764532 | 2nd | I | Any (DDL3 +) | Mono |
| NCT04471727 | DLL3/CD3 | HPN328 | 2nd | I/II | Any (DDL3 +) | Mono |
| SSA/PRRT | ||||||
| NCT02409849 | SSTR | Octreotide-LAR | 1st | II | GEP | Mono |
| NCT00978211 | 90Y-/177Lu-Dotatate-TOC | Any | II | Any (SSTR2 +) | Mono | |
| NCT04525638 | 177Lu-Dotatate | 1st or 2nd | II | GEP, lung, or UK | Nivo + 177Lu-Dotatate | |
| NCT02936323 | PEN-221 | 2nd | I/Iia | Any (SSTR2 +) | Mono | |
| Others | ||||||
| NCT02250885 | XPO1 | Selinexor | 2nd | II | GEP, lung, or UK | Mono |
| NCT05126433 | RNA polymerase II | Lurbinectedin | 2nd | II | Any | Mono |
Abbreviations: NCT number, ClinicalTrials.gov Identifier; GEP, gastro-entero-pancreatic; NEC, neuroendocrine carcinoma; UK, unknown; Mono, monotherapy; TEM, temozolomide; CDDP, cisplatin; CBDCA, carboplatin; nab-PTX, nanoparticle albumin-bound-paclitaxel; Sin, sintilimab (anti-PD-1 Ab); Nivo, nivolumab (anti-PD-1 Ab); Ipi, ipilimumab (anti-CTLA-4 Ab); CPT-11, irinotecan, TPT, topotecan; ETP, etoposide; 5-FU, 5-fluorouracil; LV, leucovorin; SSA, synthetic somatostatin analog; PRRT, peptide receptor radionuclide therapy; SSTR, somatostatin receptor; LAR, long acting release; XPO, exportin-1; Anlotinib, a tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and KIT; Surufatinib, a small molecule kinase inhibitor of VEGFR1–3, FGFR1, and CSF-1R; Cabozantinib, a small molecule inhibitor of MET, VEGFR, RET, KIT, and the TAM (TYRO3, AXL, MER) family of receptor kinases; IBI310, anti-CTLA-4 Ab; FOLFIRI, 5-fluorouracil + leucovorin + irinotecan; PLX038, pegylated topoisomerase inhibitor SN-38; Dostarlimab, anti-PD-1 Ab; Apatinib, an inhibitor of VEGFR2; XmAb20717, a humanized bispecific monoclonal antibody of PD-1 and CTLA-4; BI 764532, DLL3/CD3 bispecific T-cell engager; HPN328, DLL3/CD3 bispecific T-cell engager