Dose Finding Study of [177Lu]Lu-NeoB in Newly Diagnosed Glioblastoma and in Recurrent Glioblastoma

NCT ID: NCT05739942

Last Updated: 2025-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-15

Study Completion Date

2032-07-01

Brief Summary

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This study will investigate different doses of \[177Lu\]Lu-NeoB in combination with RT and TMZ in participants with newly diagnosed glioblastoma, with methylated or unmethylated promoter, to assess the safety and efficacy of \[177Lu\]Lu-NeoB in combination with the SoC and in recurrent glioblastoma as single agent, to identify the recommended dose and to also explore the safety of the PET imaging agent \[68Ga\]Ga-NeoB and characterize its uptake in the tumor area.

Detailed Description

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Newly diagnosed glioblastoma:

Glioblastoma is the most common and aggressive type of primary brain tumor, with a high mortality rate. The current standard of care (SoC) in newly diagnosed glioblastoma includes the combination of the alkylating agent Temozolomide (TMZ) with Radiotherapy (RT). The hypothesis of this study is to improve the outcome for participants by combining the current standard of care with the radioligand therapy \[177Lu\]Lu-NeoB. Participants with newly diagnosed glioblastoma enrolled into this trial will be treated with the standard regimen TMZ and RT, combined with \[177Lu\]Lu-NeoB every 4 weeks (Q4W) for 6 administrations. In cases where participants tolerate and benefit from \[177Lu\]Lu-NeoB, they can receive an additional 4 doses (total up to 10 dose administrations). During this period, regular safety and efficacy assessments are planned on a weekly basis. The primary objective of this trial is to identify the recommended dose of \[177Lu\]Lu-NeoB in combination with TMZ and RT in participants with newly diagnosed glioblastoma and to characterize the safety and tolerability of this treatment. For this reason, participants will be enrolled and treated in cohorts with increasing dose levels and the totality of available data will be used to define the recommended dose. Contrast enhanced MRI assessments are to be repeated every 8 weeks. Following treatment, all participants will be followed for up to 5 additional years for safety, progression of disease and survival. Participants with newly diagnosed glioblastoma will undergo a baseline \[68Ga\]Ga-NeoB PET/CT or PET/MRI after the surgery/biopsy of the tumor.

Recurrent glioblastoma:

Participants with recurrent glioblastoma carry a dismal prognosis and a short survival. The primary objective in recurrent glioblastoma is to determine the recommended dose of \[177Lu\]Lu-NeoB as single agent and to characterize the safety and tolerability of this treatment. For this reason, participants will be enrolled and treated in cohorts with increasing dose levels and the totality of available data will be used to define the recommended dose. In this study, all participants with recurrent glioblastoma will undergo \[68Ga\]Ga-NeoB PET scan to assess GRPR expression during the screening period. \[177Lu\]Lu-NeoB will be administered as a single dose every 3 weeks (Q3W) for 6 administrations. Up to 4 additional administrations of \[177Lu\]Lu-NeoB may be considered if participants tolerate and benefit from \[177Lu\]Lu-NeoB (total up to 10 dose administrations).

Conditions

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Newly Diagnosed and Recurrent Glioblastoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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[177Lu]Lu-NeoB in Combination with Radiotherapy (RT) and Temozolomide (TMZ)

In newly diagnosed glioblastoma

Group Type EXPERIMENTAL

[177Lu]Lu-NeoB

Intervention Type DRUG

Radiopharmaceutical solution for infusion

[68Ga]Ga-NeoB

Intervention Type DRUG

Either provided as Kit for the radiopharmaceutical preparation of \[68Ga\]Ga-NeoB or as ready to use radiopharmaceutical solution for injection

Temozolomide

Intervention Type OTHER

Capsules/ lyophilized powder in single-dose vial for reconstitution.

[177Lu]Lu-NeoB as Single Agent

In recurrent glioblastoma

Group Type EXPERIMENTAL

[177Lu]Lu-NeoB

Intervention Type DRUG

Radiopharmaceutical solution for infusion

[68Ga]Ga-NeoB

Intervention Type DRUG

Either provided as Kit for the radiopharmaceutical preparation of \[68Ga\]Ga-NeoB or as ready to use radiopharmaceutical solution for injection

Interventions

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[177Lu]Lu-NeoB

Radiopharmaceutical solution for infusion

Intervention Type DRUG

[68Ga]Ga-NeoB

Either provided as Kit for the radiopharmaceutical preparation of \[68Ga\]Ga-NeoB or as ready to use radiopharmaceutical solution for injection

Intervention Type DRUG

Temozolomide

Capsules/ lyophilized powder in single-dose vial for reconstitution.

Intervention Type OTHER

Other Intervention Names

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Lu-NeoB Ga-NeoB

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study
2. Age \>= 18 years
3. Histologically confirmed glioblastoma according to WHO classification established following either a surgical resection or biopsy
4. Participants who are receiving corticosteroid treatment with dexamethasone, must be treated with a dose of =\<4 mg/day (or other corticosteroids at equivalent dose) for a minimum of 7 days before initiation of study treatment
5. Adequate bone marrow and organ function as defined by the following laboratory values obtained prior to receiving the first study treatment:

1. Absolute Neutrophil Count (ANC) \>= 1.5 x 10\^9/L
2. Platelet count \>= 100 x 10\^9/L
3. Hemoglobin \>= 10.0 g/dL
4. Creatinine clearance \>= 60 mL/min calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation .
5. Aspartate transaminase (AST) or Alanine transaminase (ALT) =\< 3.0 x ULN
6. Total bilirubin (TBIL) \< 1.5 × ULN (any elevated bilirubin should be asymptomatic at enrollment) except for participants with Gilbert's syndrome who may only be included if the total bilirubin is =\< 3.0 × ULN or direct bilirubin =\< 1.5 × ULN
7. Serum lipase ≤ 1.5 x ULN. For serum lipase \> ULN - =\< 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis


9\. Availability of tumor tissue representative of glioblastoma from definitive surgery or biopsy, to support biomarker analysis 10. Presence of gadolinium enhancement at the tumor region in the pre-surgery MRI


14\. If a second surgery is performed for glioblastoma recurrence, the following criteria must be met:

1. residual and measurable disease post-surgery is not required but surgery must have confirmed the recurrence diagnosis by MRI.
2. surgery completed at least 2 weeks prior to study treatment initiation, with post-surgery recovery without any complications related to surgical procedure.

Exclusion Criteria

1\. Additional, concurrent, or active therapy for glioblastoma outside of the present study 4. History or current diagnosis of impaired cardiac function, clinically significant cardiac disease, or ECG abnormalities indicating significant risk of safety for study participants such as:

a. Documented myocardial infarction (MI), angina pectoris, cardiomyopathy, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry b. Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: i. Risk factors for Torsade de Pointes (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ii. Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsade de Pointes that cannot be discontinued or replaced by safe alternative medication (e.g., within 5 half-lives or 7 days prior to starting study drug) iii. Inability to determine the Fridericia QT correction formula (QTcF) interval c. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third-degree AV block) d. Resting QTcF \>= 450 msec (male) or \>= 460 msec (female) e. Left Ventricular Ejection Fraction (LVEF) \<50% as determined by echocardiogram (ECHO) or Multiple Gated Acquisition (MUGA) scan f. Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) \>=160 mmHg and/or Diastolic Blood Pressure (DBP) \>=100 mm Hg, with or without anti-hypertensive medication.

5\. History of another active malignancy in the previous 3 years prior to study entry, except participants with prior history of superficial bladder cancer, any in situ carcinoma or basal or squamous cell skin cancer treated curatively


17\. Any prior treatment for glioma of any grade, including: prolifeprospan 20 with carmustine wafer, intracerebral agent, radiation treatment, chemotherapy or immunotherapy
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of California LA

Los Angeles, California, United States

Site Status RECRUITING

University of Colorado Denver

Aurora, Colorado, United States

Site Status ACTIVE_NOT_RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Ctr

New York, New York, United States

Site Status RECRUITING

Univ Hosp Cleveland Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

Uni of Utah Huntsman Cancer Inst

Salt Lake City, Utah, United States

Site Status RECRUITING

Novartis Investigative Site

Dijon, Cote D Or, France

Site Status RECRUITING

Novartis Investigative Site

Marseille, , France

Site Status RECRUITING

Novartis Investigative Site

Cologne, North Rhine-Westphalia, Germany

Site Status RECRUITING

Novartis Investigative Site

Essen, , Germany

Site Status RECRUITING

Novartis Investigative Site

München, , Germany

Site Status RECRUITING

Novartis Investigative Site

Rostock, , Germany

Site Status RECRUITING

Novartis Investigative Site

Jerusalem, , Israel

Site Status RECRUITING

Novartis Investigative Site

Reggio Emilia, RE, Italy

Site Status RECRUITING

Novartis Investigative Site

Porto, , Portugal

Site Status RECRUITING

Novartis Investigative Site

Granada, Andalusia, Spain

Site Status RECRUITING

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status RECRUITING

Novartis Investigative Site

Badalona, Catalonia, Spain

Site Status RECRUITING

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status RECRUITING

Novartis Investigative Site

Madrid, , Spain

Site Status RECRUITING

Novartis Investigative Site

Madrid, , Spain

Site Status RECRUITING

Novartis Investigative Site

Liverpool, , United Kingdom

Site Status RECRUITING

Countries

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United States France Germany Israel Italy Portugal Spain United Kingdom

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

1-888-669-6682

Novartis Pharmaceuticals

Role: CONTACT

+41613241111

Facility Contacts

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Kameron Simon

Role: primary

Kayla Lane

Role: primary

904-953-7648

Alyssa Russ

Role: primary

Noah Siegel

Role: primary

212-639-3854

Sierra Ambers

Role: primary

216-844-7164

Yuri Kida

Role: primary

801-587-0272

Other Identifiers

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2022-502134-10-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CAAA603C12101

Identifier Type: -

Identifier Source: org_study_id

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