[177Lu]Lu-NeoB for Glioblastoma

Recruiting at 26 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: QT-prolonging drugs

Disqualifiers: Cardiac disease, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

Duration: 24-40 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called [177Lu]Lu-NeoB, a targeted radiotherapy, for glioblastoma, a type of brain cancer. The study aims to determine the optimal dose and assess its safety and effectiveness when combined with standard treatments like radiotherapy and temozolomide for newly diagnosed cases, or when used alone for recurrent cases. Additionally, it will evaluate the effectiveness of a new imaging agent in highlighting the tumor. Individuals recently diagnosed with glioblastoma or those with recurrent cases who have received standard treatments might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that if you are on corticosteroids like dexamethasone, you must be on a stable dose of 4 mg/day or less for at least 7 days before starting the study treatment. Also, if you are taking medications that affect the heart's QT interval, you may need to stop or replace them with safer alternatives.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that [177Lu]Lu-NeoB is generally well-tolerated, but concerns exist about its effects on the kidneys. Earlier research suggests that multiple doses might harm the kidneys. However, this information comes from earlier studies, and more data from current trials will help clarify these safety concerns. Prospective participants should discuss these potential risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for glioblastoma, which often include surgery, radiation, and chemotherapy, [177Lu]Lu-NeoB uses a novel approach known as targeted radioligand therapy. This treatment involves a radioactive substance, [177Lu]Lu, that specifically targets tumor cells, potentially increasing the precision of radiation delivery and sparing healthy tissue. Researchers are excited because this method might offer more effective targeting of cancer cells, reducing side effects and possibly improving outcomes for patients with both newly diagnosed and recurrent glioblastoma.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that treatments using lutetium-177, such as [177Lu]Lu-NeoB, effectively treat various cancers. For example, a similar treatment, [177Lu]Lu-DOTATATE, produced positive results in glioma patients, with some experiencing tumor size reduction. This trial will evaluate [177Lu]Lu-NeoB in two treatment arms: one combining it with radiotherapy and Temozolomide for newly diagnosed glioblastoma, and another using it as a single agent for recurrent glioblastoma. Additionally, lutetium-177 is already used to diagnose and treat other cancers, including prostate and stomach cancer. These findings suggest that [177Lu]Lu-NeoB could be effective for glioblastoma patients. ^{2 4 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed or recurrent glioblastoma. Participants must have stable organ and bone marrow function, a Karnofsky performance status of at least 60%, and be able to give informed consent. They should not have severe liver issues (with specific lab value limits) and if on steroids, they need to be on a low dose for at least a week before the study.

Inclusion Criteria

You must voluntarily agree to participate in the study after being fully informed of all relevant information.

My diagnosis of Glioblastoma was confirmed through surgery or biopsy.

My recent tests show my organs and bone marrow are functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants with newly diagnosed glioblastoma receive [177Lu]Lu-NeoB in combination with RT and TMZ every 4 weeks for 6 administrations, with up to 4 additional doses if tolerated. Recurrent glioblastoma participants receive [177Lu]Lu-NeoB as a single agent every 3 weeks for 6 administrations, with up to 4 additional doses if tolerated.

24-40 weeks

Weekly safety and efficacy assessments

Follow-up

Participants are monitored for safety, progression of disease, and survival after treatment

Up to 5 years

Regular visits every 8 weeks for MRI assessments

What Are the Treatments Tested in This Trial?

Interventions

• [177Lu]Lu-NeoB
• [68Ga]Ga-NeoB

Trial Overview [177Lu]Lu-NeoB in combination with radiation therapy (RT) and Temozolomide (TMZ) is being tested in new glioblastoma cases, while [177Lu]Lu-NeoB alone is tested in recurrent cases. The study also examines the safety of PET imaging agent [68Ga]Ga-NeoB and its uptake in tumors.

How Is the Trial Designed?

Group I: [177Lu]Lu-NeoB in Combination with Radiotherapy (RT) and Temozolomide (TMZ) Experimental Treatment 3 Interventions

In newly diagnosed glioblastoma

Group II: [177Lu]Lu-NeoB as Single Agent Experimental Treatment 2 Interventions

In recurrent glioblastoma

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

The novel radiopharmaceutical agent 177Lu-DOTA-DG was successfully synthesized with a high radiochemical yield and demonstrated excellent stability in human serum for up to 120 hours, indicating its potential for safe use in cancer imaging and therapy.

In preclinical studies, 177Lu-DOTA-DG caused significantly more DNA damage in cancer cells compared to untreated cells, suggesting its efficacy as a targeted treatment for cancer tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. Zhang, J., Wang, Z., Liu, H., et al.[2019]

Intracavitary radioimmunotherapy (iRIT) using 177Lu-labeled 6A10-Fab fragments was administered to three glioblastoma patients after standard treatment, showing no relevant leakage or therapy-related toxicities, indicating a promising safety profile.

Two out of three patients completed the full treatment cycles without significant adverse effects, and dosimetry confirmed that doses to organs at risk remained within safe limits, supporting the feasibility of this novel treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study. Roll, W., Müther, M., Böning, G., et al.[2023]

Lutetium-177 is a key radioisotope used in treating various cancers and other disorders, with advancements in its production and application over the last decade, particularly through direct neutron activation in research reactors.

The review highlights the development of stable 177Lu-based radiopharmaceuticals, emphasizing their clinical utility and potential benefits for cancer patients, especially in developing countries with limited access to advanced medical facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of advances in the last decade on targeted cancer therapy using 177Lu: focusing on 177Lu produced by the direct neutron activation route. Chakravarty, R., Chakraborty, S.[2023]

In a phase IIa trial involving 21 children with high-risk neuroblastoma, the treatment with 177-lutetium DOTATATE (LuDO) showed no objective responses after four courses, leading to the conclusion that this treatment schedule is not recommended for this condition.

Despite the lack of objective responses, the treatment did not result in significant toxicities, indicating that while LuDO may not be effective as a single agent, it could still have potential value in different treatment contexts or schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa trial of molecular radiotherapy with 177-lutetium DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma. Gains, JE., Moroz, V., Aldridge, MD., et al.[2021]

177Lu is a promising radionuclide for therapy due to its favorable decay characteristics, achieving high yields of approximately 4 TBq/g from natural lutetium and 110 TBq/g from enriched lutetium after neutron bombardment.

The production process results in nearly 100% radionuclidic purity, making 177Lu a reliable option for therapeutic applications, with minimal impurities detected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production logistics of 177Lu for radionuclide therapy. Pillai, MR., Chakraborty, S., Das, T., et al.[2019]

The study involving 21 patients with recurrent glioblastoma demonstrated that treatment with [225Ac]Ac-DOTA-SP is safe and well tolerated, even at higher doses of 30 MBq, with only mild temporary side effects reported.

The median overall survival time after diagnosis of recurrence was 13.2 months, indicating that while the treatment is well tolerated, the overall survival benefits need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation study of targeted alpha therapy with [225Ac]Ac-DOTA-substance P in recurrence glioblastoma - safety and efficacy. Królicki, L., Bruchertseifer, F., Kunikowska, J., et al.[2021]

The novel PSMA-targeted radioligand [177Lu]Lu-PSMA-ALB-56 was well tolerated in 10 patients with metastatic castration-resistant prostate cancer, showing no severe adverse events and indicating a favorable safety profile.

This treatment demonstrated significantly higher tumor uptake compared to other PSMA radioligands, with up to 2.3-fold increased doses in tumor lesions, suggesting potential for improved therapeutic efficacy in future applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC. Kramer, V., Fernández, R., Lehnert, W., et al.[2021]

Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) has become a promising treatment option for neuroendocrine tumors and prostate cancer, with Lutathera® and Pluvicto® being key approved therapies.

The review emphasizes the need for comprehensive safety data and optimized procedures for using 177Lu radiopharmaceuticals, aiming to improve the risk-benefit balance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. Ladrière, T., Faudemer, J., Levigoureux, E., et al.[2023]

A 34-year-old man with recurrent glioblastoma was treated with 2 cycles of low-dose [177Lu]Lu-PSMA after other treatment options were exhausted, showing intense PSMA signal in the tumor, indicating potential effectiveness.

The case suggests that [177Lu]Lu-PSMA therapy could be a promising treatment avenue for glioblastoma, warranting further investigation into its efficacy and safety in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Interval, Low-Dose [ 177 Lu]Lu-Prostate-Specific Membrane Antigen in the Treatment of Refractory Glioblastoma. More, S., Naiker, T., Jacobs, N., et al.[2023]

The combination of the p53 stabilizing peptide VIP116 and the radiotherapy agent [177Lu]Lu-DOTATATE significantly improved median survival in mice with neuroblastoma, extending it to over 120 days compared to 90 days for VIP116 and 96.5 days for [177Lu]Lu-DOTATATE alone.

Importantly, none of the treatments caused significant kidney damage, indicating a favorable safety profile, while also enhancing the effectiveness of the therapy by targeting key processes like apoptosis and angiogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

p53 stabilisation potentiates [177Lu]Lu-DOTATATE treatment in neuroblastoma xenografts. Berglund, H., Salomonsson, SL., Mohajershojai, T., et al.[2023]

NCA-LuTATE, a radiolabeled peptide used for treating neuroendocrine tumors, has been administered safely in 39 injections across 13 patients, showing an acceptable radiation safety profile with an average kidney dose of 3.1 Gy per treatment cycle.

The study found that the clearance of NCA-LuTATE is influenced by the patient's kidney function, which is important for estimating radiation doses, and it produces less radioactive waste compared to traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate. Bailey, DL., Hennessy, TM., Willowson, KP., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05739942

NCT05739942 | Dose Finding Study of [177Lu]Lu-NeoB in ... This study will investigate different doses of [177Lu]Lu-NeoB in combination with RT and TMZ in participants with newly diagnosed glioblastoma.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11631073/

Targeted radionuclide therapy for gliomas: Emerging clinical ... A subsequent study explored the efficacy of [177Lu]Lu-DOTATATE in 8 patients each with newly diagnosed or recurrent glioma and reported 2 complete and 3 partial ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11002837/

Current clinical application of lutetium‑177 in solid tumors ... As a result, 177Lu can be used for both diagnosis and treatment for diseases such as prostatic and gastric cancer. Therefore, based on the available data, the ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/lutetium-lu-177-neob?pn=1

Clinical Trials Using Lutetium Lu 177-NeoB - NCI NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying lutetium lu 177-neob.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03872778

Study Details | NCT03872778 | [177Lu]-NeoB in Patients ... The purpose of this first-in-human (FIH) study of [177Lu]-NeoB is to characterize the safety, tolerability, pharmacokinetics (PK) as well as the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9605926/

Safety of [177Lu]Lu-NeoB treatment: a preclinical study ... In general, repeated administration of [ 177 Lu]Lu-NeoB was tolerated. The most significant radiotoxic effects were found in the kidneys.

7. clinicaltrials.eu clinicaltrials.eu/inn/lutetium-177lu-neobomb1/

Lutetium (177Lu)-Neobomb1 – Application in Therapy and ... Two significant clinical trials are currently underway to evaluate the safety and efficacy of LUTETIUM (177LU)-NEOBOMB1: A Phase I/II trial combining [177Lu]- ...

8. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_9/S208/7728373

Targeted radionuclide therapy for gliomas: Emerging clinical ... A dose-finding study and evaluation of [177Lu]Lu-DOTATATE in combination with standard of care in newly diagnosed glioblastoma and as a single ...