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

A Phase I/IIa Open-label, Multi-center Study to Evaluate the Safety, Tolerabiity, Whole-body Distribution, Radiation Dosimetry and Anti-tumor Activity of [177Lu]-NeoB Administered in Patients With Advanced Solid Tumors Known to Overexpress Gastrin-releasing Peptide Receptor (GRPR)

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: [177Lu]-NeoB; Drug: [68Ga]-NeoB; Drug: LCZ696

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Medical University of Innsbruck
• France
  • La Tronche, France
    • CHU de Grenoble
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus MC
• Spain
  • Barcelona, Spain
    • Vall d'Hebron Institute of Oncology
• United Kingdom
  • Cambridge, United Kingdom
    • Addenbroke's hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Stanford, California, United States, 94305
      • Stanford University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pittsburgh University
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: [177Lu]-NeoB; [177Lu]-NeoB: peptide receptor radionuclide therapy; Other Names: Lutetium NeoB; AAA603; Drug: [68Ga]-NeoB; [68Ga]-NeoB radioactive diagnostic agent; Other Names: Gallium NeoB
Experimental: 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.	Drug: [177Lu]-NeoB; [177Lu]-NeoB: peptide receptor radionuclide therapy; Other Names: Lutetium NeoB; AAA603; Drug: [68Ga]-NeoB; [68Ga]-NeoB radioactive diagnostic agent; Other Names: Gallium NeoB
Experimental: 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.	Drug: [177Lu]-NeoB; [177Lu]-NeoB: peptide receptor radionuclide therapy; Other Names: Lutetium NeoB; AAA603; Drug: [68Ga]-NeoB; [68Ga]-NeoB radioactive diagnostic agent; Other Names: Gallium NeoB
Experimental: 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.	Drug: [177Lu]-NeoB; [177Lu]-NeoB: peptide receptor radionuclide therapy; Other Names: Lutetium NeoB; AAA603; Drug: [68Ga]-NeoB; [68Ga]-NeoB radioactive diagnostic agent; Other Names: Gallium NeoB
Experimental: 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.	Drug: [177Lu]-NeoB; [177Lu]-NeoB: peptide receptor radionuclide therapy; Other Names: Lutetium NeoB; AAA603; Drug: [68Ga]-NeoB; [68Ga]-NeoB radioactive diagnostic agent; Other Names: Gallium NeoB
Experimental: 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.	Drug: [177Lu]-NeoB; [177Lu]-NeoB: peptide receptor radionuclide therapy; Other Names: Lutetium NeoB; AAA603; Drug: [68Ga]-NeoB; [68Ga]-NeoB radioactive diagnostic agent; Other Names: Gallium NeoB
Experimental: 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.	Drug: [177Lu]-NeoB; [177Lu]-NeoB: peptide receptor radionuclide therapy; Other Names: Lutetium NeoB; AAA603; Drug: [68Ga]-NeoB; [68Ga]-NeoB radioactive diagnostic agent; Other Names: Gallium NeoB
Experimental: 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.	Drug: [177Lu]-NeoB; [177Lu]-NeoB: peptide receptor radionuclide therapy; Other Names: Lutetium NeoB; AAA603; Drug: [68Ga]-NeoB; [68Ga]-NeoB radioactive diagnostic agent; Other Names: Gallium NeoB; Drug: LCZ696; dose strength 49/51 mg, film-coated tablets for oral use; Other Names: valsartan; sacubitril

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Incidence of dose limiting toxicities (DLTs) of [177Lu]-NeoB	A dose-limiting toxicity (DLT) is defined as a clinically relevant adverse event or abnormal laboratory value not attributable to the disease or disease-related processes under investigation, considered possibly related to [177Lu]-NeoB that occurs within 42 days following the first administration of [177Lu]-NeoB (cycle 1) and meets any of the criteria listed in Table 6-4 (Criteria for defining dose-limiting toxicities).	Within 42 days following the first administration of [177Lu]-NeoB
Phase I: Determination of Maximum Tolerated Dose (MTD)/ Recommended phase two dose (RP2D) of [177Lu]-NeoB	The maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of [177Lu]-NeoB will be identified: MTD is defined as the lowest single dose at which 25% or more of the patients experienced a DLT during the first cycle (6 weeks).; RP2D is defined as the single dose level below the MTD. The number of cycles recommended for Phase II will be defined based on the cumulative dose toxicities reported during Phase I.	Within 42 days following the first administration of [177Lu]-NeoB
Phase IIa (Cohorts A, B and C): Individual clinical responses assessed by Response Evaluation Criteria In Solid Tumors (RECIST v1.1)	To assess the anti-tumor activity of [177Lu]-NeoB at the RP2D across different solid tumors	25 months
Phase IIa (Cohort E): Absorbed radiation doses of [177Lu]-NeoB in organs and tumor lesions	Absorbed radiation doses in organs and tumor lesions will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.	6 weeks
Phase IIa (Cohort E): Concentration of [177Lu]-NeoB in blood over time and derived PK parameters	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Concentration of [177Lu]-NeoB will be listed and summarized using descriptive statistics.	6 weeks
Phase I: identify maximum tolerated and/or recommended Phase II dose		18 months
Phase II: assess disease control rate 20 weeks after completion of treatment		18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival		18 months
Phase I: Tissue Activity Curves (ACs)	Tissue activity curves (ACs) will be generated from the amount of radioactivity in one given tissue at a given moment over the amount of radioactivity present in the blood at that given moment.	6 weeks
Phase I: Time Activity Curves (ACs)	Time Activity Curves (ACs) describe the percentage of the activity injected versus time.	6 weeks
Phase I: Absorbed radiation doses of [177Lu]-NeoB in critical organs	Absorbed radiation doses in critical organs (e.g. kidneys, bone marrow, pancreas) will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.	6 weeks
Phase I: Urinary excretion of [177Lu]-NeoB	Urine samples will be collected over specified time intervals and analyzed for radioactivity using a gamma counter. The radioactivity excreted in urine will be summarized using descriptive statistics.	6 weeks
Phase I: Half-life of [177Lu]-NeoB in blood	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics.	6 weeks
Phase I: Residence time of [177Lu]-NeoB in organs and tumor lesions	Residence time in organs and tumors lesions will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.	6 weeks
Phase I: Individual objective response and Duration of Response (DOR)	DOR is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause.	25 months
Phase IIa (Cohorts A, B and C): Absorbed radiation doses of [177Lu]-NeoB in organs and tumor lesions	Absorbed radiation doses in organs and tumor lesions will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.	6 weeks
Phase IIa (Cohorts A, B and C): Concentration of [177Lu]-NeoB in blood over time and derived PK parameters	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Concentration of [177Lu]-NeoB will be listed and summarized using descriptive statistics.	6 weeks
Phase IIa (Cohorts A, B and C): Changes from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).	15 months
Phase IIa (Cohort E): Adverse Events for [177Lu]-NeoB when co-administered with the NEPi LCZ696 in Cycle 1	The distribution of adverse events for [177Lu]-NeoB when co-administered with the neprilysin inhibitor (NEPi) LCZ696 will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.	25 months
Phase IIa (Cohort E): Dose interruptions and modifications for [177Lu]-NeoB when co-administered with the NEPi LCZ696 in Cycle 1		Within 42 days following the first administration of [177Lu]-NeoB (Cycle 1)
Phase I and Phase IIa: Adverse Events for [177Lu]-NeoB	The distribution of adverse events for [177Lu]-NeoB as monotherapy will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.	25 months
Phase I and Phase IIa: Adverse Events for [68Ga]-NeoB	The distribution of adverse events for [68Ga]-NeoB will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.	25 months
Phase I and Phase IIa: Dose interruptions and modifications		25 months
Determine Tissue Activity Curves (ACs) [177Lu-NeoB]	ratio of radioactivity in tissue vs blood	18 months
Determine Time Activity Curves	ratio of % activity injected vs time	18 months
Absorbed radiation dose	absorbed radiation dose to critical organs	18 months
Urinary excretion of [177Lu]-NeoB	measure amount of [177Lu]-NeoB excreted in Urine	18 months
Blood Half-life of [177Lu]-NeoB		18 months
Organ Residence time of [177Lu]-NeoB		18 months
Objective Response Rate		18 months
Duration of Response		18 months
Adverse Events [177Lu-NeoB]		18 months
Dose modifications		18 months
Adverse Events [68Ga-NeoB]		18 months

Collaborators and Investigators

• Sponsor: Advanced Accelerator Applications
• Investigators: Study Director: Study Director, Advanced Accelerator Applications; Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2019
• Primary Completion (Actual): January 7, 2025
• Study Completion (Actual): November 27, 2025

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 11, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Advanced solid tumors; GRPR; radiation dosimetry; AAA603; [177Lu]-NeoB; [68Ga]-neoB; whole-body distribution; anti-tumor activity; Overexpress gastrin-releasing peptide receptor; Lutetium-177 (177Lu)
• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Amino Acids; Amino Acids, Essential; Tetrazoles; Valine; Amino Acids, Branched-Chain; Valsartan; sacubitril and valsartan sodium hydrate drug combination; sacubitril
• Other Study ID Numbers: CAAA603A12101; 2023-507170-41-00 (Registry Identifier: EU CTIS number)

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