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[177Lu]Lu-DOTA-TATE plus octreotide LAR for newly diagnosed SSTR‑positive advanced GEP‑NET

A Phase III Multi-center, Randomized, Open-label Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients Newly Diagnosed With Grade 1 and Grade 2 (Ki-67 <10%) Advanced GEP-NET With High Disease Burden (NETTER-3)

Phase 3 Interventional Novartis · NCT06784752

This trial will test whether adding [177Lu]Lu‑DOTA‑TATE to octreotide LAR helps people newly diagnosed with somatostatin receptor–positive, well‑differentiated (G1/G2, Ki‑67 <10%) advanced gastroenteropancreatic neuroendocrine tumors who have a high disease burden.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment240 (estimated)
Ages12 Years to 100 Years
SexAll
SponsorNovartis Industry-sponsored
Drugs / interventionschemotherapy, radiation
Locations65 sites (Scottsdale, Arizona and 64 other locations)
Trial IDNCT06784752 on ClinicalTrials.gov

What this trial studies

This randomized Phase 3 trial compares [177Lu]Lu‑DOTA‑TATE plus octreotide LAR versus octreotide LAR alone in patients with newly diagnosed, SSTR‑positive, well‑differentiated (G1/G2, Ki‑67 <10%) advanced GEP‑NET and high disease burden. The study includes screening, a treatment phase with the assigned regimen, and a follow‑up phase to monitor safety and disease outcomes. Key eligibility requires histologically confirmed unresectable or metastatic GEP‑NET diagnosed within 6 months, demonstrated SSTR positivity, and investigator‑determined high disease burden. Primary and secondary endpoints focus on efficacy (tumor control/progression) and safety measures to see if adding radioligand therapy improves outcomes compared with octreotide alone.

Who should consider this trial

Good fit: Ideal candidates are adults with newly diagnosed, SSTR‑positive, well‑differentiated (G1/G2, Ki‑67 <10%) unresectable or metastatic GEP‑NET diagnosed within 6 months who have a high disease burden as judged by the investigator.

Not a fit: Patients unlikely to benefit include those with SSTR‑negative disease, higher‑grade (G3) tumors or Ki‑67 ≥10%, resectable disease, or contraindications to radionuclide therapy or somatostatin analogues.

Why it matters

Potential benefit: If successful, adding [177Lu]Lu‑DOTA‑TATE could improve tumor control, delay progression, and extend symptom relief compared with octreotide LAR alone.

How similar studies have performed: Prior randomized trials of peptide receptor radionuclide therapy (notably NETTER‑1) showed meaningful benefit in midgut NETs, so this approach builds on proven PRRT effectiveness though its use as first‑line therapy in high‑burden GEP‑NET is less established.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Presence of metastasized or locally advanced, unresectable (curative intent), histologically proven, well differentiated Grade 1 or Grade 2 (Ki-67 \<10%) gastroenteropancreatic neuroendocrine tumor (GEP-NET) diagnosed within 6 months prior to screening.
* Participants with high disease burden in the Investigator's opinion. Following criteria should be used as the guiding principle for determining high disease burden:

  * Primary tumor or a metastatic lesion \> 4 cm
  * More than one tumor or metastatic lesions measuring \> 2 cm
  * Elevated alkaline phosphatase \> 2.5 X upper limit of normal (ULN)
  * Presence of bone metastasis
  * Presence of peritoneal metastasis
  * Symptoms due to tumor volume such as pain, fatigue, weight loss, anorexia etc.
  * Symptoms due to hormone excess requiring active management
  * Additionally, participants who, in the Investigator's opinion, have high disease burden due to their disease characteristics not specified above could also be considered eligible.
* Participants ≥ 12 years of age.
* RLI somatostatin receptor (SSTR) uptake on all target lesions (defined by RECIST v1.1 criteria) at least as high as normal liver uptake assessed within 3 months prior to randomization. Any of the RLI modalities as available (some examples are listed below) can be used as per local practice:

  * \[68Ga\]Ga-DOTA-TOC PET/CT or PET/MRI
  * \[68Ga\]Ga-DOTA-TATE PET/CT or PET/MRI
  * \[64Cu\]Cu-DOTA-TATE PET/CT or PET/MRI
  * Somatostatin receptor scintigraphy (SRS) (planar and/or SPECT/CT) with \[111In\]In-pentetreotide
  * SRS (planar and/or SPECT/CT) with \[99mTc\]Tc-octreotide.
* Adequate bone marrow and organ function as defined by the following laboratory values prior to receiving the first study treatment:

  * White blood cell (WBC) count ≥ 2 x 109/L
  * Platelet count ≥ 75 x 109/L
  * Hemoglobin (Hb) ≥ 8 g/dL
  * Creatinine clearance \> 40 mL/min calculated by the Cockcroft Gault method
  * Total bilirubin ≤ 3 x ULN
  * Potassium within normal limits. Potassium level of up to 6.0 millimoles per liter (mmol/L) is acceptable at study entry if associated with creatinine clearance within normal limits calculated using Cockcroft-Gault formula. Mild decrease (grade 1) below lower limit of normal (LLN) is acceptable at study entry if considered not clinically significant by Investigator.
* ECOG performance status 0-1.
* Presence of at least 1 measurable site of disease.

Exclusion Criteria:

* Prior administration of a therapeutic radiopharmaceutical for GEP-NET at any time prior to randomization in the study.
* Any previous therapy with interferons, mTOR-inhibitors, chemotherapy or other systemic therapies except somatostatin analogues (SSAs) of GEP-NET. If as per Investigator's opinion a participant is candidate for such therapies, such participant must not be enrolled.
* Participant who received more than 4 cycles of prior SSAs (e.g., octreotide long-acting release) are not eligible. In addition, any participant receiving treatment with short-acting octreotide, which cannot be interrupted for 24 h before the administration of \[177Lu\]Lu-DOTA-TATE, or any participant receiving treatment with SSAs, which cannot be interrupted for at least 4 weeks before the administration of \[177Lu\]Lu-DOTA-TATE.
* Documented RECIST v1.1 progression during previous SSA treatments for the current GEP-NET at any time prior to randomization.
* Any previous radioembolization, chemoembolization and radiofrequency ablation for GEP-NET.
* Any major surgery within 12 weeks prior to randomization in the study.
* Known brain metastases.
* Participant with known intolerance to CT scans with intravenous (i.v.) contrast due to allergic reaction or renal insufficiency. If such a participant can be imaged with MRI, then the participant would not be excluded.
* Hypersensitivity to any somatostatin analogues, to the Investigational Medicinal Products (IMPs) active substance or to any of the excipients.
* Active severe urinary incontinence, severe voiding dysfunction, or urinary obstruction requiring an indwelling/condom catheter that, in the judgment of the Investigator, could prevent adhering to radiation safety instructions.

Other protocol-defined Inclusion/Exclusion criteria may apply.

Where this trial is running

Scottsdale, Arizona and 64 other locations

+15 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Somatostatin Receptor PositiveGastroenteropancreatic Neuroendocrine TumorSSTR+GEP-NETKi-67 <10%AAA601[177Lu]Lu-DOTA-TATEnewly diagnosed
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.