[177Lu]Lu-NeoB for Glioblastoma

Recruiting at 19 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

Trial Summary

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.

What data supports the effectiveness of the treatment [177Lu]Lu-NeoB for glioblastoma?

Research on similar treatments, like [177Lu]Lu-DOTATATE and [177Lu]-DOTA-Octreotate, shows that lutetium-177 can be effective in targeting cancer cells, as it is used in treating neuroendocrine tumors and meningiomas. Additionally, a pilot study on glioblastoma using a different lutetium-177 therapy showed promise in improving tumor control. ^{1 2 3 4 5}

Is [177Lu]Lu-NeoB safe for use in humans?

There is no specific safety data available for [177Lu]Lu-NeoB, but Lutetium-177 based treatments have been used safely in other conditions, such as prostate cancer and neuroendocrine tumors, with ongoing research to optimize their safety and effectiveness. ^{1 6 7 8 9}

What makes the drug [177Lu]Lu-NeoB unique for treating glioblastoma?

The drug [177Lu]Lu-NeoB is unique because it uses lutetium-177, a radioactive substance, to target and treat cancer cells, potentially offering a novel approach for glioblastoma treatment by combining imaging and therapy in one agent. ^{1 2 5 10 11}

What is the purpose of this trial?

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.

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Greece 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. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

p53 stabilisation potentiates [177Lu]Lu-DOTATATE treatment in neuroblastoma xenografts. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Dose escalation study of targeted alpha therapy with [225Ac]Ac-DOTA-substance P in recurrence glioblastoma - safety and efficacy. [2021]

4. Germany 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. [2023]

5. Iran pubmed.ncbi.nlm.nih.gov

In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate. [2020]

6. United States 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. [2023]

7. Germany 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. [2021]

8. Germany 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. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Production logistics of 177Lu for radionuclide therapy. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Short-Interval, Low-Dose [ 177 Lu]Lu-Prostate-Specific Membrane Antigen in the Treatment of Refractory Glioblastoma. [2023]