Table 6.
Clinical trials of immune checkpoint inhibitors in NEC
| Trials | Target | Agent | Line | Phase | Treatment | Primary sites | Key outcomes | Ref |
|---|---|---|---|---|---|---|---|---|
| NCT03278405 | PD-L1 | Avelumab (Avel) | 1st | II | Mono | GEP or lung | Among 10 GEP and pulmonary NECs in NET001 cohort, 9 were GEP-NECs. In all patients, ORR, 0%; mPFS, 2.0 months; mOS, 5.7 months | 210 |
| NCT03352934 | 2nd | II | Mono | Any | Among 29 patients with G3 NENs, 16 and 19 were NECs and GEP-G3 NENs, respectively. In an interim analysis, the DCR after 8 weeks was 32% (PR of two); mOS, 4.2 months | 213 | ||
| NCT02939651 | PD-1 | Pembrolizumab (Pembro) | 2nd | II | Mono | Any | Among 29 patients with G3 NEN, 24 and 19 were GEP-NENs and NECs, respectively. In all patients, ORR was 3.4%; mPFS, 8.9 weeks; mOS, 20.4 weeks. Only one patient with a large cell esophageal NEC had an objective PR that was ongoing for 13 months | 209 |
| NCT03136055 | 2nd | II | Mono | Any | Among 14 NECs after failure of previous therapy, 6 were GEP-NECs. In all patients, ORR, 7%; mPFS, 58 days. Because more than 2 of 14 patients did not respond by week 18 in the stage-1 part, the stage-2 part for additional patient enrollment was terminated | 211 | ||
| NCT03136055 | 2nd | II | Pembro + chemo (CPT-11 or PTX) | Any | Among 22 NECs after failure of previous therapy, 16 were GEP-NECs. Chemotherapy: 17 CPT-11 and 5 PTX. In all patients, ORR, 9%; mPFS, 2 months; mOS, 4 months | 244 | ||
| NCT03167853 | Toripalimab (Tori) | 2nd | I | Mono | Any | Among 40 NENs (Ki-67 ≥ 10%) after failure of previous therapy, 32 were NECs, including 25 GEP-NECs. ORR, 18.7% in NEC and 25.0% in NET. In all patients, the mPFS and mOS were 2.5 and 7.8 months, respectively | 214 | |
| NCT03879057 | 2nd | I | Tori + surufatinib | Any | Among 22 patients with NENs, 14 were NECs. In 13 evaluable NECs, ORR, 23.1%; mPFS, 4.0 months; mOS, 7.5 months | 246 | ||
| NCT04169672 | 2nd | II | Tori + surufatinib | Any | In 20 evaluable NECs, ORR, 20%; DCR, 70%; mPFS, 3.94 months | 247 | ||
| NCT02955069 | Spartalizumab (Spa) | 2nd | II | mono | GEP | Among 116 NENs after failure of previous therapy, 21 were GEP-NECs. ORR, 4.8% in GEP-NEC, and 7.4% in NET. In GEP-NEC, mPFS and mOS were 1.8 and 6.8 months, respectively | 212 | |
| NCT03980925 | Nivolumab (Nivo) | 1st | II | Nivo + CBDCA + ETP | GEP or UK | Among 38 patients with G3 GEP or unknown NENs in the first-line setting, 26 and 31 were NECs and GEP-NENs, respectively. In all patients, ORR was 54.1%; mPFS, 5.7 months; mOS, 13.9 months. The 12-month OS rate was 58.3% and 54.7% in NETs and NECs, respectively | 243 | |
| NCT03728361 | 1st | II | Nivo + TEM | Any | Among 28 NENs, 14 and 8 were GEP-NENs and NECs, respectively. ORR, 38% in NEC and 35% in NET. In the NECs, mPFS and mOS were 6.9 and 32.3 months, respectively | 239 | ||
| NCT03591731 | 2nd | II (randomized parallel arms) | mono | GEP or lung | Among 91 refractory pulmonary LCNECs or GEP-NECs after failure of previous therapy, 46 were GEP-NECs. ORR at 8 weeks, 7.1% in GEP-NEC, and 7.3% in pulmonary LCNEC. In all patients, the mPFS and mOS were 1.8 and 7.2 months, respectively. The primary endpoint, ORR at 8 weeks, was not met | 208 | ||
| PD-1/CTLA-4 | Nivolumab (Nivo) + ipilimumab (Ipi) | 2nd | Nivo + Ipi | Among 94 refractory pulmonary (large-cell only) or GEP-NECs after failure of previous therapy, 46 were GEP-NECs. ORR at 8 weeks, 11.6% in GEP-NEC, and 18.2% in pulmonary LCNEC. In all patients, the mPFS and mOS were 1.9 and 5.8 months, respectively. The primary endpoint, ORR at 8 weeks, was met | 208 | |||
| NCT02834013 | 2nd | II (basket trial, multiple cohorts) | Nivo + Ipi | Any | Among 32 patients with non-pancreatic NEN, 15 and 18 were GEP-NENs and NECs, respectively. ORR, 44% in NEC and 0% in NET. In all patients, mPFS and mOS were 4 and 11 months, respectively. 6-month PFS rate of 44% in NEC and 14% in NET | 234 | ||
| 2nd | Nivo + Ipi | Among 19 patients with G3 NEN, 9 and 11 were GEP-NENs and NECs, respectively. In all patients, ORR, 26%; mPFS, 2.0 months; mOS, 8.9 months | 235 | |||||
| NCT02923934 | 1st | II | Nivo + Ipi | Any | Among 29 patients with NENs, 6 and 4 were GEP-NETs and GEP-NECs, respectively. ORR, 50% in GEP-NEC and 33% in GEP-NET. In all patients, ORR, 24%; mPFS, 4.8 months; mOS, 14.8 months | 236 | ||
| NCT03095274 | PD-L1/CTLA-4 | Durvalumab (Durva) + tremelimumab (Treme) | 2nd | II (multiple cohorts) | Durva + Treme | GEP | Among 33 patients with GEP-NENs after first line platinum-based chemotherapy, 18 and 15 were GEP-NECs and GEP-G3 NETs, respectively. In all patients, ORR was 9.1%; mPFS, 2.4 months; mOS, 5.9 months. The primary endpoint, the 9-month OS rate, was met | 217 |
Abbreviations: NCT number, ClinicalTrials.gov Identifier; GEP, gastro-entero-pancreatic; NEC, neuroendocrine carcinoma; NEN, neuroendocrine neoplasm; NET, neuroendocrine tumor; UK, unknown; ORR, overall response rate; mPFS, median progression-free survival; mOS, median overall survival; DCR, disease control rate; Ref, reference; Mono, monotherapy