[177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-neoB Lesion Uptake

NCT ID: NCT03872778

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-24
• Study Completion Date: 2025-11-27

Brief Summary

First in Human (FIH) study to characterize the safety, tolerability, pharmacokinetics (PK), distribution, radiation dosimetry, and anti-tumor activity of [177Lu]-NeoB in patients with advanced solid tumors known to overexpress GRPR and with [68Ga]-NeoB lesion uptake.

Detailed Description

This study was designed to establish whether the ligand NeoB, a high affinity antagonist for GRPR, could be used in a theragnostic approach for selection and therapy of GRPRexpressing malignancies: radiolabeled with (1) Gallium 68 (68Ga) to identify lesions and with (2) Lutetium-177 (177Lu) for the treatment of these lesions.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase II Cohort E (Breast, Prostate, GIST)

These participants were eligible for enrollment in any of the three advanced/metastatic tumor type (as defined for cohorts A,B,C. The participants received the 5.55 GBq (150mCi) +/- 10% of \[177Lu\]-NeoB and neprilysin inhibitor (NEPi) LCZ696 in cycle 1 and then 9.25 GBq (250mCi) +/- 10% of \[177Lu\]-NeoB once every 6 weeks for at least 3 cycles.

Group Type: EXPERIMENTAL

[177Lu]-NeoB

Intervention Type: DRUG

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

[68Ga]-NeoB

Intervention Type: DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

LCZ696

Intervention Type: DRUG

dose strength 49/51 mg, film-coated tablets for oral use

Phase I Cohort 1 (DL1(50mCi + 150mCi)

Participants received the 1.85 GBq (50mCi) +/- 10% of \[177Lu\]-NeoB at cycle 1 and then received 5.55 GBq (150mCi）+/- 10% of \[177Lu\]-NeoB for at least 3 cycles.

Group Type: EXPERIMENTAL

[177Lu]-NeoB

Intervention Type: DRUG

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

[68Ga]-NeoB

Intervention Type: DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

Phase I Cohort 2 (DL2 200mCi)

Participants received the 9.25 GBq (250mCi) +/- 10% of \[177Lu\]-NeoB once every 6 weeks for at least 3 cycles.

Group Type: EXPERIMENTAL

[177Lu]-NeoB

Intervention Type: DRUG

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

[68Ga]-NeoB

Intervention Type: DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

Phase I Cohort 3 (DL3 250mCi)

Participants received the 11.1 GBq (300mCi) +/- 10% of \[177Lu\]-NeoB once every 6 weeks for at least 3 cycles.

Group Type: EXPERIMENTAL

[177Lu]-NeoB

Intervention Type: DRUG

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

[68Ga]-NeoB

Intervention Type: DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

Phase II Cohort A (Breast Cancer)

Participants received the 9.25 GBq (250mCi) +/- 10% of \[177Lu\]-NeoB once every 6 weeks for at least 3 cycles.

Group Type: EXPERIMENTAL

[177Lu]-NeoB

Intervention Type: DRUG

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

[68Ga]-NeoB

Intervention Type: DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

Phase II Cohort B (Prostate Cancer)

Participants received the 9.25 GBq (250mCi) +/- 10% of \[177Lu\]-NeoB once every 6 weeks for at least 3 cycles.

Group Type: EXPERIMENTAL

[177Lu]-NeoB

Intervention Type: DRUG

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

[68Ga]-NeoB

Intervention Type: DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

Phase II Cohort C (Gastro Intestinal Stromal Tumor (GIST))

Participants received the 9.25 GBq (250mCi) +/- 10% of \[177Lu\]-NeoB once every 6 weeks for at least 3 cycles.

Group Type: EXPERIMENTAL

[177Lu]-NeoB

Intervention Type: DRUG

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

[68Ga]-NeoB

Intervention Type: DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

Phase II Cohort D (Renal Impairment)

These were participants with any advanced/metastatic solid tumor type, and with moderate impaired renal function. The participants received the 9.25 GBq (250mCi) +/- 10% of \[177Lu\]-NeoB once every 6 weeks for at least 3 cycles.

Group Type: EXPERIMENTAL

[177Lu]-NeoB

Intervention Type: DRUG

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

[68Ga]-NeoB

Intervention Type: DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

Interventions

[177Lu]-NeoB

\[177Lu\]-NeoB: peptide receptor radionuclide therapy

Intervention Type: DRUG

[68Ga]-NeoB

\[68Ga\]-NeoB radioactive diagnostic agent

Intervention Type: DRUG

LCZ696

dose strength 49/51 mg, film-coated tablets for oral use

Intervention Type: DRUG

Other Intervention Names

Lutetium NeoB, AAA603; Gallium NeoB; sacubitril/valsartan

Eligibility Criteria

Inclusion Criteria

• Signed informed consent prior to participation
• Adult patients with advanced solid tumors known to overexpress GRPR
• [68Ga]-NeoB tumor lesion uptake on PET/CT or PET/MRI scan at screening visit (>50% of lesions detected with conventional imaging are identified as well by [68Ga]-NeoB uptake)
• At least one measurable lesion per RECIST 1.1/RANO with a [68Ga]-NeoB uptake
• Patients for whom no standard therapy is available, tolerated or appropriate
• Presence of at least one tumor lesion confirmed with functional or structural imaging (PET, SPECT, CT, MRI, bone scan) within 2 months prior to study entry
• Patient Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Life expectancy more than 6 months.

Exclusion Criteria

• Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 60 mL/min or serum creatinine > 1.5 x ULN.
• Platelet count of < 75 x 10e9/L
• Absolute neutrophil count (ANC) < 1.0 x 10e9/L
• Hemoglobin < 9 g/dL
• alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) if no demonstrable liver metastases of > 5 x ULN in the presence of liver metastases
• Total bilirubin > 1.5 ULN, except for patients with documented Gilbert's syndrome who are eligible if total bilirubin ≤ x ULN
• Serum amylase and/or lipase > 1.5 ULN
• Known or expected hypersensitivity to [177Lu]-NeoB, [68Ga]-NeoB or any of their excipients
• Impaired cardiac function or clinically significant cardiac disease, including any of the following:

• Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association (NHYA) grade ≥2), uncontrolled arterial hypertension or clinically significant arrhythmia
• LVEF < 50% as determined by echocardiogram (ECHO)
• QTcF > 470 msec for females and QTcF >450 msec for males on screening electrocardiogram (ECG) or congenital long QT syndrome
• Acute myocardial infarction or unstable angina pectoris < 3 months prior to study entry
• Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting plasma glucose > 160 mg/dL (8.9 mmol/L)
• Patients with history of or ongoing acute or chronic pancreatitis
• Prior administration of a radiopharmaceutical with therapeutic intent within a period corresponding to 10 half-lives of the radionuclide used in such radiopharmaceutical
• Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone marrow
• Patients with a bone scan showing an excessive skeletal radiopharmaceutical uptake with absent or faint activity in soft tissues and the genitourinary tract due to diffuse bone/bone marrow metastases in bone scan also called a "superscan"
• Prior treatment with Radium=223
• Patients who have changed the dose of systemic steroid therapy within less than 2 weeks prior to study entry or patients for whom steroid dose increase is anticipated during the study.
• Patients who have received prior systemic anti-cancer treatment within the following time frames:

• Cyclical chemotherapy within a period that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment
• Biologic therapy (e.g. antibodies), continuous or intermittent small molecule therapeutics, or any other investigational agents within a period which is ≤ 5T1/2 or ≤ 4 weeks (whichever is longer) prior to study entry
• History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study.
• Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type
• pregnant or breast-feeding women
• women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study UNLESS they are using highly effective methods of contraception throughout the study and for 6 months after study drug discontinuation. Highly effective contraception methods include:

• Total abstinence
• Male or female sterilization
• Combination of any two of the following (a+b or a+c or b+c)

1. Use of oral, injected, or implanted hormonal methods of contraception. In case of use of oral contraception, women should be stable on the same pill for a minimum of 3 months before taking study treatment.

2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).

3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. Post-menopausal women are allowed to participate in this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum Follicle-Stimulating Hormone (FSH) levels > 40 mIU/mL [for US only: and estradiol < 20 pg/mL] or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child bearing potential. Sexually active males must use a condom during intercourse while taking the drug and for 6 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Advanced Accelerator Applications

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Study Director

Role: STUDY_DIRECTOR

Advanced Accelerator Applications

Locations

City of Hope

Duarte, California, United States

Stanford University

Stanford, California, United States

John Hopkins University

Baltimore, Maryland, United States

Oregon Health & Science University

Portland, Oregon, United States

Pittsburgh University

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

Medical University of Innsbruck

Innsbruck, , Austria

CHU de Grenoble

La Tronche, , France

Erasmus MC

Rotterdam, , Netherlands

Vall d'Hebron Institute of Oncology

Barcelona, , Spain

Addenbroke's hospital

Cambridge, , United Kingdom

Countries

United States; Austria; France; Netherlands; Spain; United Kingdom

References

Taunk NK, Escorcia FE, Lewis JS, Bodei L. Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets. Cancer J. 2024 May-Jun 01;30(3):218-223. doi: 10.1097/PPO.0000000000000720.

Reference Type: DERIVED

PMID: 38753757 (View on PubMed)

Sundlov A, Sjogreen-Gleisner K. Peptide Receptor Radionuclide Therapy - Prospects for Personalised Treatment. Clin Oncol (R Coll Radiol). 2021 Feb;33(2):92-97. doi: 10.1016/j.clon.2020.10.020. Epub 2020 Nov 12.

Reference Type: DERIVED

PMID: 33189510 (View on PubMed)

Other Identifiers

2023-507170-41-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CAAA603A12101

Identifier Type: -

Identifier Source: org_study_id