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

NCT03872778 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: CAAA603A121012023-507170-41-00
• Study Type: interventional
• Target: 35
• Locations: 6 countries
• Sites: 11

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.

Conditions

Neoplasms

Keywords

AAA603; [177Lu]-NeoB; [68Ga]-neoB; whole-body distribution; radiation dosimetry; anti-tumor activity; Advanced solid tumors; Overexpress gastrin-releasing peptide receptor; GRPR; Lutetium-177 (177Lu)

Outcome Measures

Primary Outcomes (7)

• 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: 1. 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). 2. 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 Outcomes (27)

• Phase I: Tissue Activity Curves (ACs)

  6 weeks

• Phase I: Time Activity Curves (ACs)

  6 weeks

• Phase I: Absorbed radiation doses of [177Lu]-NeoB in critical organs

  6 weeks

• Phase I: Urinary excretion of [177Lu]-NeoB

  6 weeks

• Phase I: Half-life of [177Lu]-NeoB in blood

  6 weeks

Study Arms (8)

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

EXPERIMENTAL

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; Drug: [68Ga]-NeoB

Phase I Cohort 2 (DL2 200mCi)

EXPERIMENTAL

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

Drug: [177Lu]-NeoB; Drug: [68Ga]-NeoB

Phase I Cohort 3 (DL3 250mCi)

EXPERIMENTAL

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

Drug: [177Lu]-NeoB; Drug: [68Ga]-NeoB

Phase II Cohort A (Breast Cancer)

EXPERIMENTAL

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

Drug: [177Lu]-NeoB; Drug: [68Ga]-NeoB

Phase II Cohort B (Prostate Cancer)

EXPERIMENTAL

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

Drug: [177Lu]-NeoB; Drug: [68Ga]-NeoB

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

EXPERIMENTAL

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

Drug: [177Lu]-NeoB; Drug: [68Ga]-NeoB

Phase II Cohort D (Renal Impairment)

EXPERIMENTAL

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; Drug: [68Ga]-NeoB

Phase II Cohort E (Breast, Prostate, GIST)

EXPERIMENTAL

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; Drug: [68Ga]-NeoB; Drug: LCZ696

Interventions

[177Lu]-NeoB DRUG

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

Also known as: Lutetium NeoB, AAA603

Phase I Cohort 1 (DL1(50mCi + 150mCi); Phase I Cohort 2 (DL2 200mCi); Phase I Cohort 3 (DL3 250mCi); Phase II Cohort A (Breast Cancer); Phase II Cohort B (Prostate Cancer); Phase II Cohort C (Gastro Intestinal Stromal Tumor (GIST)); Phase II Cohort D (Renal Impairment); Phase II Cohort E (Breast, Prostate, GIST)

[68Ga]-NeoB DRUG

\[68Ga\]-NeoB radioactive diagnostic agent

Also known as: Gallium NeoB

Phase I Cohort 1 (DL1(50mCi + 150mCi); Phase I Cohort 2 (DL2 200mCi); Phase I Cohort 3 (DL3 250mCi); Phase II Cohort A (Breast Cancer); Phase II Cohort B (Prostate Cancer); Phase II Cohort C (Gastro Intestinal Stromal Tumor (GIST)); Phase II Cohort D (Renal Impairment); Phase II Cohort E (Breast, Prostate, GIST)

LCZ696 DRUG

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

Also known as: sacubitril, valsartan

Phase II Cohort E (Breast, Prostate, GIST)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Advanced Accelerator Applications: lead

Study Sites (11)

City of Hope

Duarte, California, 91010, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

John Hopkins University

Baltimore, Maryland, 21287, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Pittsburgh University

Pittsburgh, Pennsylvania, 15213, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical University of Innsbruck

Innsbruck, Austria

Location

CHU de Grenoble

La Tronche, France

Location

Erasmus MC

Rotterdam, Netherlands

Location

Vall d'Hebron Institute of Oncology

Barcelona, Spain

Location

Addenbroke's hospital

Cambridge, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 38753757 DERIVED

• 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.

  PMID: 33189510 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

sacubitril and valsartan sodium hydrate drug combination; sacubitril; Valsartan

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Study Director

  Advanced Accelerator Applications

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I: dose range finding to identify Recommended Phase II Dose Phase IIa: assessment of anti-tumor activity

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 13, 2019
• Study Start: May 24, 2019
• Primary Completion: January 7, 2025
• Study Completion: November 27, 2025
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (6); ES (1); AU (1); GB (1); FR (1); NL (1)