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 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 several 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.
Combining PRRT with a DNA repair inhibitor shows early promise
A recent Phase I clinical trial explored whether adding olaparib – a drug that blocks cancer cells’ ability to repair their DNA – could enhance the effectiveness of 177Lu-DOTATATE, a form of peptide receptor radionuclide therapy (PRRT). The study included 18 adults with somatostatin receptor–positive neuroendocrine tumors, most commonly from the pancreas, small intestine, or lungs. Participants received up to four standard PRRT treatments along with increasing doses of olaparib to find the safest and most tolerable dose.
Overall, the combination was well tolerated, with most side effects being mild to moderate. The most common issue was a drop in platelet count, particularly at the highest olaparib dose. While this trial wasn’t designed to measure how well the treatment worked against tumors, it demonstrated that the two therapies can be safely given together – a key step toward future research to evaluate their impact more fully.
Key takeaways:
- The combination of 177Lu-DOTATATE and olaparib was generally safe and feasible.
- The most common side effect was low platelet count (thrombocytopenia).
- A dose of 200 mg of olaparib twice daily was recommended for future trials.
The study lays the groundwork for larger trials that may help determine whether this combination can offer greater tumor control or longer-lasting benefits for people with neuroendocrine cancer.
Read the full article from The Journal of Nuclear Medicine.
Early signals of promise from new immunotherapy for NECs
Boehringer Ingelheim reported early results of its trial of the investigational drug obrixtamig, a T-cell engager, in a Phase I study for patients with advanced pulmonary and extrapulmonary neuroendocrine carcinomas (NECs). Obrixtamig is a type of immunotherapy designed to help the immune system recognize and attack cancer cells that have a protein on their surface named DLL3. NECs tend to highly express DLL3, whereas normal cells do not, making it a good target for drug development.
The company reported early results of the study at the 2025 American Society of Clinical Oncology’s (ASCO) annual meeting. The results show encouraging signs, especially in patients whose tumors have high levels of DLL3, where 40% saw their tumors shrink. Overall, 67% of patients with high DLL3 expression had disease control. Side effects were mostly mild, with low-grade immune reactions being the most common. No serious safety concerns were reported.
Key takeaways:
- Tumor shrinkage was seen in 40% of patients with high DLL3 expression.
- Side effects were manageable, with mostly mild immune-related symptoms.
- The study will continue with further dose and safety testing.
Targeted alpha therapy shows encouraging results in early trial
Perspective Therapeutics reported new findings from its Phase 1/2a trial of [212Pb]VMT-α-NET, a targeted alpha radiation therapy designed to treat neuroendocrine tumors. This treatment delivers alpha particles directly to tumor cells, aiming to destroy them while sparing healthy tissue.
So far, the therapy appears safe, with no serious side effects reported among 42 participants. In one dose group, four out of seven patients had tumor shrinkage – including 3 with confirmed, ongoing responses. Most patients in the early groups stayed progression free for over a year.
Key takeaways:
- No significant safety issues were reported.
- Tumor shrinkage was seen in more than half of patients at one dose level.
- Many participants remained stable for over a year after treatment.
These early results suggest this new therapy may offer a safe and effective option for people with advanced neuroendocrine tumors, and further evaluation is underway.
New drug conjugate targets neuroendocrine tumors without radiation
Crinetics Pharmaceuticals is preparing to launch the first human trial of CRN09682, a new kind of non-radioactive, targeted therapy for neuroendocrine tumors. CRN09682 uses a unique small molecule linker to attach a toxic drug [monomethyl auristatin E (MMAE)] to a ligand that specifically binds to somatostatin receptor 2 (SST2) – a protein commonly found on neuroendocrine tumor cells. Once inside the cell, the drug is released directly where it’s needed, sparing healthy tissue and potentially reducing treatment side effects.
Key takeaways:
- CRN09682 delivers cancer-blocking medication directly into tumor cells.
- This approach offers a potential non-radioactive treatment option.
First patient dosed in Phase I/II trial of cancer-fighting virus for high-grade neuroendocrine cancer
Seneca Therapeutics has begun a Phase I/II clinical trial of SVV-001, an oncolytic virus-based therapy designed to kill neuroendocrine cancer cells from the inside. This is the first time the therapy is being tested alongside standard immunotherapy (nivolumab and ipilimumab) in a randomized trial. The study enrolls patients with high-grade neuroendocrine carcinomas or Grade 3 neuroendocrine tumors.
SVV-001 naturally targets a receptor found on some cancer cells. Once injected directly into a tumor, it multiplies and destroys the cancer from within, potentially making the tumor more visible to the immune system. The study is evaluating different dose levels and combinations with immunotherapy to find the safest and most effective approach.
Key takeaways:
- SVV-001 is being tested with immunotherapy in a Phase I/II trial for aggressive neuroendocrine cancer.
- The virus is designed to infect and destroy cancer cells while boosting an immune response.
To explore current clinical trials, visit NETRF’s Clinical Trial Finder.