Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients With Grade 1 and Grade 2 Advanced GEP-NET (NETTER-3)

April 28, 2026 updated by: Novartis Pharmaceuticals

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)

The purpose of the current study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-TATE plus octreotide long-acting release (LAR) versus octreotide LAR alone in newly diagnosed patients with somatostatin receptor positive (SSTR+), well differentiated Grade1 and Grade 2 (G1 and G2) (Ki-67 <10%) advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with high disease burden

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study consists of a screening phase, a treatment phase and a follow-up phase. This study compares treatment with [177Lu]Lu-DOTA-TATE plus octreotide LAR and octreotide LAR only.

Study Type

Interventional

Enrollment (Estimated)

240

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Recruiting
        • Novartis Investigative Site
    • Ontario
      • London, Ontario, Canada, N6A 5W9
        • Recruiting
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • Novartis Investigative Site
  • China
      • Beijing, China, 100036
        • Recruiting
        • Novartis Investigative Site
      • Beijing, China, 100730
        • Recruiting
        • Novartis Investigative Site
      • Beijing, China, 102200
        • Recruiting
        • Novartis Investigative Site
      • Shanghai, China, 200032
        • Recruiting
        • Novartis Investigative Site
  • France
      • Bron, France, 69677
        • Recruiting
        • Novartis Investigative Site
      • Clichy, France, 92110
        • Recruiting
        • Novartis Investigative Site
      • Montpellier, France, 34298
        • Recruiting
        • Novartis Investigative Site
      • Nantes, France, 44093
        • Recruiting
        • Novartis Investigative Site
      • Pessac, France, 33604
        • Recruiting
        • Novartis Investigative Site
      • Toulouse, France, 31059
        • Recruiting
        • Novartis Investigative Site
  • Germany
      • Erlangen, Germany, 91054
        • Recruiting
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Recruiting
        • Novartis Investigative Site
      • München, Germany, 80377
        • Recruiting
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, H-1083
        • Recruiting
        • Novartis Investigative Site
      • Szeged, Hungary, 6725
        • Recruiting
        • Novartis Investigative Site
  • Italy
      • Milan, Italy, 20141
        • Recruiting
        • Novartis Investigative Site
    • FE
      • Cona, FE, Italy, 44124
        • Recruiting
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italy, 16132
        • Recruiting
        • Novartis Investigative Site
    • MI
      • Milan, MI, Italy, 20133
        • Recruiting
        • Novartis Investigative Site
      • Rozzano, MI, Italy, 20089
        • Recruiting
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Italy, 56126
        • Recruiting
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00189
        • Recruiting
        • Novartis Investigative Site
      • Roma, RM, Italy, 00168
        • Recruiting
        • Novartis Investigative Site
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • Recruiting
        • Novartis Investigative Site
    • South Holland
      • Rotterdam, South Holland, Netherlands, 3015 GD
        • Recruiting
        • Novartis Investigative Site
  • Poland
      • Gdansk, Poland, 80-214
        • Recruiting
        • Novartis Investigative Site
      • Gliwice, Poland, 44 101
        • Recruiting
        • Novartis Investigative Site
      • Krakow, Poland, 30-688
        • Recruiting
        • Novartis Investigative Site
      • Poznan, Poland, 60-355
        • Recruiting
        • Novartis Investigative Site
      • Warsaw, Poland, 02-351
        • Recruiting
        • Novartis Investigative Site
      • Warsaw, Poland, 04-141
        • Recruiting
        • Novartis Investigative Site
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Novartis Investigative Site
      • Seoul, South Korea, 05505
        • Recruiting
        • Novartis Investigative Site
      • Seoul, South Korea, 03722
        • Recruiting
        • Novartis Investigative Site
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Novartis Investigative Site
      • Madrid, Spain, 28041
        • Recruiting
        • Novartis Investigative Site
      • Madrid, Spain, 28034
        • Recruiting
        • Novartis Investigative Site
      • Madrid, Spain, 28040
        • Recruiting
        • Novartis Investigative Site
      • Salamanca, Spain, 37007
        • Recruiting
        • Novartis Investigative Site
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Recruiting
        • Novartis Investigative Site
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Spain, 33011
        • Recruiting
        • Novartis Investigative Site
  • United Kingdom
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • Novartis Investigative Site
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic Arizona
        • Contact:
        • Principal Investigator:
          • Mohamad Sonbol
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Recruiting
        • Highlands Oncology Group
        • Principal Investigator:
          • Joseph Thaddeus Beck
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Rocky Mountain Cancer Centers
        • Principal Investigator:
          • Allen Cohn
        • Contact:
    • Connecticut
      • Hartford, Connecticut, United States, 06102
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale New Haven Hospital
        • Principal Investigator:
          • Pamela Kunz
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Jacksonville
        • Principal Investigator:
          • Jason Starr
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Winship Cancer Institute
        • Contact:
        • Principal Investigator:
          • Amol Takalkar
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Recruiting
        • LSU Medical Center
        • Principal Investigator:
          • Mary Maluccio
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48202-2689
        • Recruiting
        • Henry Ford Hospital
        • Principal Investigator:
          • Philip A Philip
        • Contact:
    • New York
      • New York, New York, United States, 10029-6574
        • Recruiting
        • Mount Sinai Medical Center
        • Principal Investigator:
          • Edward Wolin
        • Contact:
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Tennessee Oncology
        • Principal Investigator:
          • Joseph Merriman
        • Contact:
    • Texas
      • Austin, Texas, United States, 78705
        • Active, not recruiting
        • TxO Austin Midtown
      • Dallas, Texas, United States, 75251
    • Virginia
      • Fairfax, Virginia, United States, 22031
      • Norfolk, Virginia, United States, 23502
        • Recruiting
        • Virginia Oncology Associates
        • Contact:
        • Principal Investigator:
          • Jedrzej Wykretowicz
      • Wytheville, Virginia, United States, 24382
    • Washington
      • Tacoma, Washington, United States, 98405
        • Recruiting
        • Northwest Medical Specialties
        • Contact:
        • Principal Investigator:
          • Mohammed N Kanaan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Octreotide LAR
Participants in this arm will receive Octreotide LAR only.
Drug: Octreotide LAR

Octreotide LAR will be administered Q8W when co-administered with [177Lu]Lu-DOTA-TATE in the investigational arm followed by Q4W.

In the control arm Octreotide LAR will be administered Q4W.

Other Names:
  • SOM230
Experimental: [177Lu]Lu-DOTA-TATE + Octreotide LAR
Participants in this arm will receive [177Lu]Lu-DOTA-TATE plus Octreotide long-acting release (LAR).
Radiation: [177Lu]Lu-DOTA-TATE
[177Lu]Lu-DOTA-TATE will be administered 4 times during treatment period with frequency of every 8 weeks (Q8W)
Drug: Octreotide LAR

Octreotide LAR will be administered Q8W when co-administered with [177Lu]Lu-DOTA-TATE in the investigational arm followed by Q4W.

In the control arm Octreotide LAR will be administered Q4W.

Other Names:
  • SOM230

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) centrally assessed by Blinded Independent Review Committee (BIRC)
Time Frame: After observing approximately 88 PFS events as per BIRC assessments, expected after approximately 33 months from study start
PFS is defined as the time from randomization to the first occurrence of progression (centrally assessed by Blinded Independent Review Committee (BIRC) according to RECIST v1.1) or death due to any cause.
After observing approximately 88 PFS events as per BIRC assessments, expected after approximately 33 months from study start

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Deterioration (TDD) (Key Secondary)
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Time to deterioration is defined as the time from randomization to the first occurrence of a deterioration compared to the baseline scores or death from any cause for each of the following domains (tested separately) of EORTC QLQ-GI.NET21 [gastrointestinal scale (GI scale)] and EORTC QLQ-C30 questionnaires (fatigue, diarrhea, and global health scale).
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Progression Free Survival (PFS)
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
PFS is defined as the time from randomization to the first occurrence of progression (Investigator assessed according to RECIST v1.1) or death due to any cause.
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Objective Response Rate (ORR)
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
ORR: Rate of participants with best overall response (BOR) of partial response (PR) or complete response (CR) as per RECIST v1.1 (both Investigator and centrally assessed by BIRC).
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Disease Control Rate (DCR)
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
DCR: Rate of participants with BOR of PR, CR or stable disease (SD) as per RECIST v1.1 (both Investigator and centrally assessed by BIRC).
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Duration of Response (DOR)
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
DOR: The time from initially meeting the criteria for response (CR or PR) until the time of progression according to RECIST v1.1 or death due to underlying disease only.
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Overall Survival (OS)
Time Frame: Until 60 month from randomization
OS: Time from the randomization date until the date of death due to any cause.
Until 60 month from randomization
Time to Deterioration (TDD)
Time Frame: At the time of primary PFS analysis after observing approximately 88 PFS events per BIRC assessment
TTD is the time from randomization to the first occurrence of a deterioration compared to the baseline scores or death from any cause for EORTC QLQ-G.I.NET21 and EORTC QLQ-C30 domains not included among key secondary endpoints.
At the time of primary PFS analysis after observing approximately 88 PFS events per BIRC assessment
Absolute change from baseline in EORTC QLQ-G.I.NET21 domain
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Quality of Life assessed by EORTC QLQ-G.I.NET21 (excluding GI scale) (domains not included as key secondary objectives)
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Absolute change from baseline in the EQ-5D-5L index at each time point
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Quality of Life assessed by EQ-5D-5L
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Absolute change from baseline in EORTC QLQ-C30 domain
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start.
Quality of Life assessed by EORTC QLQ-C30 (domains not included as key secondary objectives)
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start.
Dosimetry
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Absorbed radiation dose in selected organs, tumor lesions and total body
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Pharmacokinetic (PK) parameter: Area Under Curve (AUC) from [177Lu]Lu-DOTA-TATE blood radioactivity data
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start

The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1).

The AUC from time zero to infinity (mass x time x volume-1)
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
PK parameter: Clearance from [177Lu]Lu-DOTA-TATE blood radioactivity data
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
Clearance is the total body clearance of drug from the plasma or blood (volume x time-1).
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
PK parameter: Distribution volume (Vz) from [177Lu]Lu-DOTA-TATE blood radioactivity data
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
The apparent volume of distribution during terminal phase (associated with λz) (volume)
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
PK parameter: half-life (T1/2) from [177Lu]Lu-DOTA-TATE blood radioactivity data
Time Frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start
The elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time). Use qualifier for other half-lives
After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 30, 2025

Primary Completion (Estimated)

December 8, 2028

Study Completion (Estimated)

January 23, 2034

Study Registration Dates

First Submitted

December 19, 2024

First Submitted That Met QC Criteria

January 15, 2025

First Posted (Actual)

January 20, 2025

Study Record Updates

Last Update Posted (Actual)

April 30, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAAA601A62301
  • 2024-518325-15-00 (Registry Identifier: EU CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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