Table 1.
Ongoing RCT for ICIs in GEP-NENs
| ClinicalTrials.gov Identifier | Molecule | Study phase | Assigned intervention | Primary outcome(s) | Estimated enrollment, n | Estimated study completion date | Trial status |
|---|---|---|---|---|---|---|---|
|
Phase Ib/II Study of Pembrolizumab With Lanreotide Depot for Gastroenteropancreatic Neuroendocrine Tumors |
Pembrolizumab | Phase Ib—II | Pembrolizumab 200 mg intravenous every 3 weeks and lanreotide depot 90 mg subcutaneous every 3 weeks | Objective response rate | 22 | June 1, 2021 | Active, not recruiting |
|
A Phase II Trial of Pembrolizumab in Combination With Cisplatin or Carboplatin and Etoposide in Chemotherapy naïve Patients With Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung (Excluding Small Cell) Neuroendocrine Carcinoma |
Pembrolizumab | Phase II | Pembrolizumab 200 mg with Carboplatin or Cisplatin plus etoposide. Repeat 4–6 cycles followed by Pembrolizumab alone until progression or intolerance for up to 2 years | Progression-free survival | - | - | Withdrawn (Lack of accrual) |
|
A Pilot Study of Pembrolizumab-based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas |
Pembrolizumab | Phase II |
Part A: pembrolizumab 200 mg every three weeks Part B: pembrolizumab 200 mg every three weeks and, either - irinotecan 125 mg/m2 in a two weeks on, one week off format in 3 week cycles, or - paclitaxel 80 mg/m2 every week |
Overall response rate | 36 | July 1, 2023 | Active, not recruiting |
|
A Pilot Study of Avelumab in Unresectable/Metastatic, Progressive, Poorly Differentiated Grade 3 Neuroendocrine Carcinomas |
Avelumab | Phase I—II | Avelumab 10 mg/kg once every 2 weeks, until occurence of progressive disease, unacceptable toxicity, or any of the other criteria for withdrawal listed in the protocol | Overall response rate | 10 | March 12, 2020 | Completed |
|
Phase II Study of Avelumab in Metastatic Gastronetro-pancreatic (GEP) Neuroendocrine Carcinoma (NEC, WHO Grade 3)as Second-line Treatment After Failing to Etoposide + Cisplatin: Integration of Genomic Analysis to Identify Predictive Molecular Subtypes (MS100070-0177) |
Avelumab | Phase II | Avelumab 10 mg/kg every 2 weeks | Best response | 14 | July 22, 2019 | Completed |
|
A GCO Trial Exploring the Efficacy and Safety of Nivolumab Monotherapy or Nivolumab Plus Ipilimumab in Pre-treated Patients With Advanced, Refractory Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine |
Nivolumab / Nivolumab + Ipilimumab |
Phase II |
[arm A]: Nivolumab 3 mg/kg every 2 weeks [arm B]: Nivolumab 3 mg/kg every 2 weeks + Ipilimumab 1 mg/kg every 6 weeks |
Objective response rate | 180 | September 2023 | Recruiting |
|
A Phase II Single Arm Trial Evaluating the Preliminary Efficacy of the Combination of 177Lu-DOTATATE and Nivolumab in Grade 3 Well-differentiated Neuroendocrine Tumours (NET) or Poorly Differentiated Neuroendocrine Carcinomas (NEC) |
Nivolumab | Phase II | Nivolumab 240 mg and 7.4 GBq 177Lu-DOTATATE intravenously as a 4-h infusion | Overall response rate | 30 | September 30, 2024 | Recruiting |
|
NCT03352934*** A Phase II, Open-label, Multicenter Trial to Investigate the Clinical Activity and Safety of Avelumab in Patients With Advanced, Metastatic High Grade Neuroendocrine Carcinomas NEC G3 (WHO 2010) Progressive After Chemotherapy |
Avelumab | Phase II | 10 mg/kg Avelumab every 2 weeks until documented disease progression (PD), unacceptable toxicity, or any criterion for treatment withdrawal are met | Disease control rate | 60 | January 2024 | Active, not recruiting |
|
A Phase 2 Study of XL184 (Cabozantinib) in Combination With Nivolumab and Ipilimumab for the Treatment of Poorly Differentiated Neuroendocrine Carcinomas |
Nivolumab + ipilimumab | Phase II |
Cabozantinib on days 1–21 of cycles 1–4 and days 1–28 of subsequent cycles; Nivolumab on day 1, and ipilimumab on day 1 of cycles 1–4 only Treatment repeats every 21 for 4 cycles then every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity |
Overall response rate | 30 | October 1, 2021 | Recruiting |
|
Pembrolizumab for the Treatment of Recurrent High Grade Neuroendocrine Carcinoma |
Pembrolizumab | Phase II | Pembrolizumab 200 mg every 3 weeks until disease recurrence or discontinuation due to unacceptable toxicity for a maximum of 2 years | Overall response rate | 6 | March 11, 2019 | Terminated (discontinued) |
|
A Phase II Study of Platinum-doublet Chemotherapy in Combination With Nivolumab as First-line Treatment in Subjects With Unresectable, Locally Advanced or Metastatic G3 Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknown (UK) Origin |
Nivolumab | Phase II |
[Induction Phase]: Nivolumab 360 mg + Carboplatin + Etoposide on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480 mg for 24 months or until PD, death or toxicity [Maintenance Phase]: Nivolumab 480 mg every 4 weeks for 2 years |
Overall survival rate | 38 | December 2022 | Recruiting |
|
Phase II Study of Pembrolizumab and Lenvatinib in Advanced Well-differentiated Neuroendocrine Tumors |
Pembrolizumab | Phase II | Pembrolizumab 200 mg every 3 weeks | Objective response rate | 30 | December 2023 | Suspended |
|
NCT03728361**** A Phase II, Multi-Cohort Trial of Combination Nivolumab and Temozolomide in Recurrent/Refractory Small-Cell Lung Cancer and Advanced Neuroendocrine Tumors |
Nivolumab | Phase II | Nivolumab on day 1 of a 28 day cycle + temozolomide on days 1–5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity | Objective response rate | 53 | December 31, 2021 | Recruiting |
|
NCT03074513***** A Phase II, Single-Arm Open-Label Study of the Combination of Atezolizumab and Bevacizumab in Rare Solid Tumors |
Atezolizumab | Phase II | Atezolizumab + Bevacizumab on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity | Objective response | 164 | March 31, 2021 | Active, not recruiting |
|
A Phase I/II Study of Regorafenib Plus Avelumab in Solid Tumors |
Avelumab | Phase I—II | Phase 1 and Phase 2: Avelumab every 2 weeks starting at Cycle 1 Day 15. Regorafenib (oral) once daily for three weeks on/one week off |
Phase I: Recommended dose of regorafenib Phase II: objective response; progression-free rate |
482 (though only one cohort out of ten is made by GEP-NETs) | May 2022 | Recruiting |
|
NCT03095274****** A Phase II Study of Durvalumab (MEDI4736) Plus Tremelimumab for the Treatment of Patients With Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin (the DUNE Trial) |
Durvalumab + Tremelimumab | Phase II |
Durvalumab 1500 mg for 12 months in patients ≥ 30 kg. durvalumab 20 mg/kg for patients < 30 kg Tremelimumab 75 mg for up to 4 doses/cycles in patients ≥ 30 kg. remelimumab 1 mg/kg for patients < 30 kg |
Clinical Benefit Rate | 126 | July 2021 | Recruiting |
|
An Open-Label Phase Ib/II Study of Surufatinib in Combination With Tislelizumab in Subjects With Advanced Solid Tumors |
Tislelizumab | Phase Ib—II |
Part 1 (dose escalation): surufatinib administered orally once daily + tislelizumab 200 mg intravenous infusion every 3 weeks Part 2 surufatinib at the Recommended Phase 2 Dose selected in Part 1 + tislelizumab 200 mg every 3 weeks |
Dose limiting toxicity; Objective response rate |
120 | April 30, 2023 | Recruiting |
|
NCT03365791******* Modular Phase 2 Study to Link Combination Immune-therapy to Patients With Advanced Solid and Hematologic Malignancies. Module 9: PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies |
Spartalizumab | Phase II | PDR001 (spartalizumab) and LAG525 will be administered via i.v. infusion over 30 min once every 3 weeks. LAG525 will be given first followed by PDR001 | Clinical Benefit Rate | 76 | September 17, 2020 | Completed |