Highlights from recent clinical trial developments in neuroendocrine cancer
Neuroendocrine cancer research continues to evolve, with a growing number of clinical trials exploring bold, highly targeted strategies aimed at treating advanced and high-grade forms of the disease. From radiopharmaceuticals and drug conjugates to viral therapies and T-cell engagers, these studies reflect the evolving science behind how we detect, target, and treat neuroendocrine cancer.
In this clinical trial roundup, NETRF highlights four studies that are testing new mechanisms, expanding the reach of existing therapies, or taking the first step into human trials. While some are still in early phases, all share a common goal: to offer new hope for patients living with neuroendocrine cancer.
- First participant dosed in Phase 1/2 trial of CRN09682 for SST2-positive tumors
Crinetics Pharmaceuticals, Inc. recently reported that the first participant has received the study drug CRN09682 in the Phase 1/2 BRAVESST2 trial. The study is enrolling participants with metastatic or locally advanced somatostatin receptor 2 (SST2)-positive neuroendocrine tumors and other SST2-expressing solid tumors. Eligible participants must have disease progression after standard therapies and confirmed SST2 expression by imaging.
CRN09682 is the lead candidate from Crinetics’ proprietary nonpeptide drug conjugate (NDC) platform. It is designed to home in on SST2 on tumor cells and act like a guided delivery system, carrying a potent cancer-killing payload into the tumor while aiming to limit spillover exposure to healthy tissues.
This first-in-human study plans to enroll up to 150 participants. It includes a dose-escalation phase to evaluate safety, tolerability, and the recommended Phase 2 dose. Phase 2 will further study the treatment in selected tumor types.
Key takeaways:
- CRN09682 is designed to target SST2-expressing tumors using a small-molecule drug conjugate that may help limit exposure to healthy tissues.
- The Phase 1/2 BRAVESST2 trial has begun dosing participants, marking the first clinical evaluation of this approach.
- The study will assess safety, pharmacokinetics, and early signals of anti-tumor activity to help guide future development.
- First participant randomized in Phase 3 CAREFNDR trial of paltusotine in carcinoid syndrome
Crinetics Pharmaceuticals, Inc. also announced that the first participant has been randomized in the pivotal Phase 3 CAREFNDR trial. This multicenter, randomized, double-blind, placebo-controlled study is evaluating once-daily oral paltusotine in adults with carcinoid syndrome caused by neuroendocrine tumors.
A once-daily pill could be a real day-to-day upgrade compared with monthly octreotide or lanreotide shots, reducing clinic visits and injection-related discomfort. If paltusotine controls symptoms as well, it could offer a simpler option that’s easier to fit into daily life and stay on long term.
The CAREFNDR trial builds on encouraging Phase 2 data showing that paltusotine led to rapid and sustained reductions in carcinoid syndrome symptoms—particularly flushing episodes and frequent bowel movements, which are two hallmark features of the condition. In this Phase 3 study, approximately 141 adults will be randomized in a 2:1 ratio to receive either paltusotine or placebo.
The trial’s primary endpoint Is the change in daily flushing episodes, with change in bowel movement frequency as a key secondary endpoint. Following the initial 16-week randomized period, participants may continue in a 104-week extension period to evaluate long-term safety, symptom control, and additional clinical outcomes such as progression-free survival.
Key takeaways:
- CAREFNDR is the first Phase 3 randomized trial evaluating once-daily oral paltusotine for carcinoid syndrome.
- The study is designed to measure both symptom relief and longer-term clinical outcomes.
- Positive results could expand the role of paltusotine beyond its current U.S. approval for acromegaly.
- FDA accepts NDA for 177Lu-edotreotide in GEP-NETs after positive Phase 3 data
The U.S. Food and Drug Administration (FDA) has the New Drug Application from ITM Radiopharma for 177Lu-edotreotide (also known as ITM-11) a targeted radiotherapeutic agent for treating gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The application is supported by data from the Phase 3 COMPETE trial, and the FDA is expected to make a regulatory decision by August 28, 2026.
In the COMPETE study, 177Lu-edotreotide was compared with everolimus in adults with inoperable, progressive, Grade 1 or Grade 2 somatostatin receptor (SSTR2)-positive GEP-NETs. The trial demonstrated that those receiving 177Lu-edotreotide experienced significantly longer median progression-free survival compared to those treated with everolimus, along with higher objective response rates. In plain terms, patients on 177Lu-edotreotide went longer before their cancer worsened, and more people saw their tumors shrink.
Key takeaways:
- The FDA has accepted the New Drug Application for 177Lu-edotreotide for adults with somatostatin receptor-–positive GEP-NETs.
- The application is supported by Phase 3 COMPETE results demonstrating longer progression-free survival versus everolimus.
- There were fewer study drug-related adverse events compared with everolimus.
- First participant dosed in Phase 1/2 SANTANA-225 trial
Ariceum Therapeutics announced that the first participant has been dosed in the Phase 1/2 SANTANA-225 clinical trial of 225Ac-SSO110. The investigational therapy is a novel radioligand, an Actinium-225-labeled SSTR2 antagonist, being studied in adults with extensive-stage small cell lung cancer (ES-SCLC) or Merkel cell carcinoma (MCC), both aggressive, poorly differentiated neuroendocrine cancers.
225Ac-SSO110 is designed to deliver targeted alpha-particle radiation to SSTR2-expressing tumor cells, aiming to maximize tumor cell kill while minimizing damage to surrounding healthy tissue, a potential advantage for aggressive neuroendocrine cancers with few durable options.
The global study will assess safety, tolerability, preliminary anti-tumor activity, and help determine a recommended Phase 2 dose. Participants include those treated with checkpoint inhibitors during first-line maintenance for ES-SCLC or first-line therapy for MCC. Ariceum has also received orphan drug designation from the FDA for 225Ac-SSO110 in ES-SCLC, highlighting the unmet need in this rare and aggressive cancer.
Key takeaways:
- The Phase 1/2 SANTANA-225 trial has begun dosing participants with targeted alpha-particle therapy 225Ac-SSO110.
- The study aims to evaluate safety, tolerability, and early signs of effectiveness while establishing dosing for future studies.
- Initial safety data are expected in 2026 and may inform further development in other SSTR2-expressing cancers.
Together, these updates show progress across the full pipeline, from first-in-human studies to a potential new FDA-approved radiotherapy for GEP-NETs. While it will take time to learn which approaches translate into meaningful benefits, each trial reflects a push toward more precise, more personalized treatment options for people living with neuroendocrine cancer. NETRF will continue tracking these studies and sharing what they may mean for patients and families as results emerge.
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To explore currently enrolling clinical trials, visit NETRF’s Clinical Trial Finder.