Clinical Trial Finder

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.

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.

Arms

Experimental: [177Lu]Lu-DOTA-TATE + Octreotide LAR

Participants in this arm will receive [177Lu]Lu-DOTA-TATE plus Octreotide long-acting release (LAR).

Active Comparator: Octreotide LAR

Participants in this arm will receive Octreotide LAR only.

Interventions

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.