Table 2.
Clinical trials assessing immunotherapy in GEP NECs
| Trial and author | N | Primary site | Treatment | Primary endpoint | ORR (%) | PFS (median) | OS (median) |
|---|---|---|---|---|---|---|---|
| First-line therapy | |||||||
|
NICE NEC trial
Riesco-Martinez et al |
38 | GEP or UKP G3 NENs |
Nivolumab + CBDCA + etoposide |
12-mo OS | 54.1% | 5.7 mo (43.2% 6-mo PFS, 17.5% 12-mo PFS) |
13.9 mo (54% 12-mo OS, 44% 18-mo OS) |
| Second-line therapy and beyond | |||||||
|
NIPINEC trial
Walter et al |
185 | 93 lung LC-NEC 92 GEP NECs |
Nivolumab vs nivolumab + ipilimumab |
ORR 8 wk | Nivo vs Nivo-Ipi: Lung: 7.3% vs 18.2% GEP: 7.1% vs 11.6% |
1.8 vs 1.9 mo | 7.2 vs 5.8 mo |
|
DUNE trial
Capdevila et al |
33 | C4: G3 GEP NENs | Durvalumab + tremelimumab | 9-moOS | 9.1% | 2.4 mo | 5.9 mo (9-mo OS 36%) |
|
CA209-538
Basket trial Klein et al |
29 | NENs any site (13 G3, 10 GEP, 4 GEP NECs) |
Nivolumab + ipilimumab | DCR | 24% (G3 31%) (DCR 72%) |
4.8 mo | 14.8 mo |
|
DART SWOG 1609
Basket trial Patel et al |
32 | NENs any site (18 G3, 15 GEP, 8 GEP NECs) |
Nivolumab + ipilimumab | ORR | 25% (G3 44%) |
4 mo (G3 6-mo PFS 44%) |
11 mo |
|
Mulvey et al
Chan et al |
14 (A) 22 (B) |
EP-NECs (6 + 16 GEP) |
Part A: Pembro Part B: Pembro + CT (IRI or PAC) |
ORR | A: 7% B: 5% |
A: 1.9 mo B: 2.0 mo |
A: NR B: 4.9 mo |
| Vijayvergia et al | 29 | G3 EP-NENs (19 NECs, 24 GEP) |
Pembrolizumab | ORR | 3.4% | 2.2 mo | 5.1 mo |
| Yao et al | 116 | 21 GEP-NECs | Spartalizumab | ORR | 4.8% | 1.8 mo | 6.8 mo |
| Lu et al | 40 | G2-3 NENs (Ki67 > 10%) (32 GEP, 32 NEC) |
Toripalimab | ORR | All patients 20% GI NEN 13% Pan NEN 22% Other primaries 38% PD-L1 > 1 50% TMB-H 75% |
2.5 mo | 7.8 mo |
|
AVENEC trial
Fottner et al |
29 | G3 NENs (21 GEP, 19 NEC) |
Avelumab | DCR | 6.9% (DCR 27.6%) |
4.0 months | 7.0 mo (NEC 4.7 mo, G3 NET NR) |
Abbreviations: CBDCA, carboplatin; CDDP, cisplatin; CT, chemotherapy; C4, cohort 4; DCR, disease control rate; EP-NEC, extrapulmonary neuroendocrine carcinoma; GEP, gastroenteropancreatic; LC-NEC, large-cell neuroendocrine carcinoma; NEC, neuroendocrine carcinoma; NEN, neuroendocrine neoplasm; NET, neuroendocrine tumors; ORR, objective response rate; NR, not reported or not reached; OS, overall survival; Pembro, pembrolizumab; PFS, progression-free survival; TMB-H, high tumor mutational burden; UKP, unknown primary.