Neuroendocrine Tumor (NET) Clinical Trials

About Neuroendocrine Tumor (NET) trials

Trial selection in NET depends first on tumor site, grade, and somatostatin receptor expression. SSTR2 (somatostatin receptor type 2) expression is the foundational biomarker for NET because most well-differentiated NETs express SSTR2 strongly, and trials of somatostatin analogs and peptide receptor radionuclide therapy (PRRT) are SSTR-driven. SSTR2 status is typically measured by Ga-68 DOTATATE PET imaging rather than by tumor sequencing. MEN1 mutations and VHL alterations identify hereditary NET syndromes (MEN1 syndrome with parathyroid, pancreatic, and pituitary tumors; von Hippel-Lindau syndrome) and gate trials specific to those syndromes. DAXX (alongside ATRX, not in this panel) is a chromatin remodeler frequently mutated in pancreatic NETs and defines a subset associated with worse prognosis. BRCA2 mutations are rare in NETs but actionable for PARP inhibitor trials when present. PD-L1 (CD274) status gates a subset of immunotherapy trials, although IO has historically had limited activity in well-differentiated NETs.

Recruiting trials in NET organize along site, grade, and SSTR expression status. Well-differentiated NET trials test PRRT combinations (Lu-177 dotatate plus checkpoint inhibitors, plus DNA repair inhibitors, or in earlier lines), alpha-PRRT (with actinium-225 or other alpha emitters in development), and novel SSTR-targeted agents. Pancreatic NET-specific trials test everolimus + new agents, sunitinib successors, and combinations targeting MEN1 / DAXX-associated biology. Poorly-differentiated NEC trials test platinum + etoposide combinations, DLL3-targeted agents (overlapping with SCLC), and novel mechanisms because high-grade NEC behaves more like SCLC than like well-differentiated NET. Grade 3 well-differentiated NET trials are an active and distinct space because these tumors fall between G1/G2 and NEC in biology. VHL-associated tumor trials enroll patients with germline VHL mutations across tumor types (RCC, NET, hemangioblastoma) and test HIF2α inhibitors.

Beyond biomarkers, NET trial eligibility depends on tumor site, differentiation and grade, and SSTR expression status. Tumor site (pancreas, midgut / small intestine, lung, gastric, or other) gates many trials. Differentiation (well-differentiated vs poorly differentiated NEC) is critical and changes which trial set applies. Grade by Ki-67 proliferation index (G1 <3%, G2 3-20%, G3 >20%) is required for many trials and stratification. SSTR expression status by Ga-68 DOTATATE PET (positive uptake required for PRRT and many SSTR-targeted trials). Prior somatostatin analog exposure (octreotide or lanreotide) is the standard front-line for well-differentiated NET, and most trials are line-defined relative to it. Prior PRRT exposure for post-PRRT trials. Prior everolimus or sunitinib for pancreatic NET later-line trials. Functional status (carcinoid syndrome present or absent) for some trials. Performance status, with most trials accepting ECOG 0-2.

Biomarkers tested in Neuroendocrine Tumor (NET) trials

These are the molecular markers most commonly required or evaluated in Neuroendocrine Tumor (NET) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.