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

NCT05739942 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CAAA603C121012022-502134-10-00
• Study Type: interventional
• Target: 40
• Locations: 8 countries
• Sites: 23

Brief Summary

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.

Conditions

Newly Diagnosed and Recurrent Glioblastoma

Keywords

Glioblastoma,; GBM,; Radioligand Therapy,; RLT,; [68Ga]Ga-NeoB,; [177Lu]Lu-NeoB,; Temozolomide,; TMZ,; O-6-methylguanine-DNA methyltransferase,; MGMT

Outcome Measures

Primary Outcomes (1)

• Incidence and nature of Dose Limiting Toxicity (DLTs)

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the DLT observation period of \[177Lu\]Lu-NeoB. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading. In Group 1 (newly diagnosed GBM), the DLT observation period is defined as a total of 8 weeks (56 days) from the first administration of \[177Lu\]Lu-NeoB, to cover the entire duration of concomitant RT and TMZ combination with the first two administrations of \[177Lu\]Lu-NeoB. In Group 2 (recurrent GBM), the DLT observation period is 6 weeks (42 days) starting from the first administration of \[177Lu\]Lu-NeoB (at Week 1 Day 1) and accounting for assessment of the safety profile during 2 full cycles of \[177Lu\]Lu-NeoB.

  Up to 8 weeks (newly diagnosed glioblastoma (GBM)) or 6 weeks (recurrent GBM) after the first administration of [177Lu]Lu-NeoB

Secondary Outcomes (12)

• Incidence and severity of Adverse Events (AEs) and serious Adverse Events (SAEs), changes in laboratory parameters, vital signs and Electrocardiogram (ECGs)

  From date of enrollment till 28 days after end of Treatment, assessed up to approximately 17 months

• Absorbed radiation doses of [177Lu]Lu-NeoB in organs and tumor lesions

  Cycles 1, 3 and 5: Day 1 (1-4 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i) (1 cycle = 3 weeks (recurrent GBM) or 4 weeks (newly diagnosed GBM))

• Concentration of [177Lu]Lu-NeoB in blood over time

  Cycle 1: Day1 (Pre-dose (before start of infusion), end of infusion, 0.5, 1, 2, 4 and 6 hours (hr) post-dose/post-infusion (p.i.)), Day2 (24 hr p.i), Day3 (48 hr p.i), Day8 (168 h p.i) (1 cycle= 3 weeks (recurrent GBM) or 4 weeks (newly diagnosed GBM))

• Observed maximum blood concentration (Cmax) of [177Lu]Lu-NeoB

  Cycle 1: Day1 (Pre-dose (before start of infusion), end of infusion, 0.5, 1, 2, 4 and 6 hours (hr) post-dose/post-infusion (p.i.)), Day2 (24 hr p.i), Day3 (48 hr p.i), Day8 (168 h p.i) (1 cycle= 3 weeks (recurrent GBM) or 4 weeks (newly diagnosed GBM))

• Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-NeoB

  Cycle 1: Day1 (Pre-dose (before start of infusion), end of infusion, 0.5, 1, 2, 4 and 6 hours (hr) post-dose/post-infusion (p.i.)), Day2 (24 hr p.i), Day3 (48 hr p.i), Day8 (168 h p.i) (1 cycle= 3 weeks (recurrent GBM) or 4 weeks (newly diagnosed GBM))

Study Arms (2)

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

EXPERIMENTAL

In newly diagnosed glioblastoma

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

[177Lu]Lu-NeoB as Single Agent

EXPERIMENTAL

In recurrent glioblastoma

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

Interventions

[68Ga]Ga-NeoB DRUG

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

Also known as: Ga-NeoB

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

Temozolomide OTHER

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

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

[177Lu]Lu-NeoB DRUG

Radiopharmaceutical solution for infusion

Also known as: Lu-NeoB

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

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study
• Age \>= 18 years
• Histologically confirmed glioblastoma according to WHO classification established following either a surgical resection or biopsy
• 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
• Adequate bone marrow and organ function as defined by the following laboratory values obtained prior to receiving the first study treatment:
• Absolute Neutrophil Count (ANC) \>= 1.5 x 10\^9/L
• Platelet count \>= 100 x 10\^9/L
• Hemoglobin \>= 10.0 g/dL
• Creatinine clearance \>= 60 mL/min calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation .
• Aspartate transaminase (AST) or Alanine transaminase (ALT) =\< 3.0 x ULN
• 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
• 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
• \. 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
• \. If a second surgery is performed for glioblastoma recurrence, the following criteria must be met:
• residual and measurable disease post-surgery is not required but surgery must have confirmed the recurrence diagnosis by MRI.

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

University of California LA

Los Angeles, California, 90095, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Ctr

New York, New York, 10065, United States

Location

Univ Hosp Cleveland Medical Center

Cleveland, Ohio, 44106-5028, United States

Location

Uni of Utah Huntsman Cancer Inst

Salt Lake City, Utah, 84103, United States

Location

Novartis Investigative Site

Dijon, Cote D Or, 21034, France

Location

Novartis Investigative Site

Marseille, 13885, France

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

München, 80377, Germany

Location

Novartis Investigative Site

Rostock, 18057, Germany

Location

Novartis Investigative Site

Jerusalem, 9112001, Israel

Location

Novartis Investigative Site

Reggio Emilia, RE, 42123, Italy

Location

Novartis Investigative Site

Porto, 4200-072, Portugal

Location

Novartis Investigative Site

Granada, Andalusia, 18014, Spain

Location

Novartis Investigative Site

Badalona, Catalonia, 08916, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Barcelona, 08907, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Liverpool, CH63 4JY, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: February 22, 2023
• Study Start: May 15, 2024
• Primary Completion (Estimated): December 10, 2026
• Study Completion (Estimated): July 1, 2032
• Last Updated: February 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); US (7); IL (1); PT (1); ES (6); FR (2); DE (4); GB (1)