Radioactive Agent for Cancer

(NeoRay Trial)

No longer recruiting at 10 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Advanced Accelerator Applications

Must not be taking: NEP inhibitors, ACE inhibitors

Disqualifiers: Uncontrolled heart disease, Diabetes, Pregnancy, others

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

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new radioactive treatment called [177Lu]-NeoB to evaluate its safety and effectiveness for individuals with certain advanced cancers. Researchers aim to understand how the treatment spreads in the body and whether it can combat tumors with specific receptors, which are proteins that can signal cancer growth. The trial includes various groups to determine the optimal dose and schedule, particularly for breast, lung, and prostate cancers. It suits patients with these cancers who have exhausted other treatments or for whom other treatments are no longer suitable. Participants must have measurable tumors that show uptake of the trial drug on scans. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving NEP inhibitors or have taken certain investigational drugs within 30 days prior to the trial. Additionally, there are restrictions on prior systemic anti-cancer treatments and radiopharmaceuticals. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are currently taking certain medications like NEP inhibitors or have recently taken investigational drugs. It's best to discuss your specific medications with the trial team.

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

Research shows that the treatment under study, [177Lu]-NeoB, is generally well-tolerated by patients. In earlier studies, most participants managed repeated doses, although some side effects occurred. The most significant effects involved the kidneys, indicating that while most patients did not experience serious issues, kidney health requires close monitoring.

These findings come from human trials assessing the treatment's safety and tolerability. The data does not reveal widespread severe side effects, suggesting that many individuals can undergo the treatment without major issues. However, as this is an early-phase trial, not all potential side effects may be known yet. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about [177Lu]-NeoB because it represents a novel approach in cancer treatment by using a radioactive agent that specifically targets tumors. Unlike existing treatments that often rely on chemotherapy or radiation, which can affect healthy cells, [177Lu]-NeoB is designed to deliver radiation directly to cancer cells, potentially minimizing damage to normal tissue. This targeted mechanism might offer improved safety and effectiveness, making it a promising option in the fight against cancer. Additionally, the incorporation of a companion diagnostic agent, [68 Ga]-NeoB, helps select patients who are most likely to benefit, potentially enhancing treatment outcomes.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that [177Lu]-NeoB, one of the treatments studied in this trial, might help treat advanced solid tumors with high levels of the Gastrin-Releasing Peptide Receptor (GRPR). Early lab studies demonstrated that different doses of [177Lu]-NeoB improved survival times in animal models with tumors. This treatment targets cancer cells with radiation, potentially shrinking tumors while sparing healthy tissues. Similar treatments using lutetium-177 have shown promise in treating advanced prostate cancer, suggesting potential benefits for other tumor types. Although initial results are encouraging, further studies are needed to determine its effectiveness in people. ^{1 2 3 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Advanced Accelerator Applications

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, especially breast, lung, prostate cancer, GIST or GBM. They must have a tumor that overexpresses GRPR and shows uptake of [68Ga]-NeoB on scans. Participants need at least one measurable lesion and no standard treatment options left. Specific criteria apply for different phases regarding prior treatments and renal function.

Inclusion Criteria

I have a metastatic tumor likely to overexpress GRPR and my kidney function is moderately impaired.

At least one measurable lesion per RECIST 1.1, RANO (GBM only) criteria on low-dose CT/MRI

I have been diagnosed with GIST.

Exclusion Criteria

I do not have any mental or physical health conditions that could affect the study.

I have had or currently have pancreatitis.

I am a woman able to have children and am not using strong birth control methods.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation (Phase I)

Participants receive escalating doses of [177Lu]-NeoB to determine the maximum tolerated dose (MTD) and recommended phase two dose (RP2D).

6 weeks per cycle

3 cycles (q6w)

Expansion (Phase IIa)

Participants receive [177Lu]-NeoB at the RP2D to assess anti-tumor activity across different solid tumors.

6 weeks per cycle

3 cycles (q6w)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

25 months

What Are the Treatments Tested in This Trial?

Interventions

• [177Lu]-NeoB
• [68Ga]-NeoB

Trial Overview

[177Lu]-NeoB is being tested to see how safe it is and how well it works in treating solid tumors with GRPR expression that absorb [68Ga]-NeoB. The trial will also look at how the body processes the drug and its effects on tumors through various imaging techniques.

How Is the Trial Designed?

Group I: Phase II Cohort E (Breast, Prostate, GIST) Experimental Treatment 3 Interventions

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.

Group II: Phase II Cohort D (Renal Impairment) Experimental Treatment 2 Interventions

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.

Group III: Phase II Cohort C (Gastro Intestinal Stromal Tumor (GIST)) Experimental Treatment 2 Interventions

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

Group IV: Phase II Cohort B (Prostate Cancer) Experimental Treatment 2 Interventions

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

Group V: Phase II Cohort A (Breast Cancer) Experimental Treatment 2 Interventions

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

Group VI: Phase I Cohort 3 (DL3 250mCi) Experimental Treatment 2 Interventions

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

Group VII: Phase I Cohort 2 (DL2 200mCi) Experimental Treatment 2 Interventions

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

Group VIII: Phase I Cohort 1 (DL1(50mCi + 150mCi) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Advanced Accelerator Applications

Lead Sponsor

Trials

37

Recruited

3,000+

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]

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]

The 177Lu-labeled immunoconjugate 177Lu-CC49 effectively delayed the growth of established human colon carcinomas in mice, demonstrating its potential as a therapeutic option for cancer treatment.

While higher doses of 177Lu-CC49 showed toxicity, a fractionated dose of 750 microCi was well tolerated and successfully eliminated tumors in 90% of treated mice, indicating a promising therapeutic window for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody-based therapy of a human tumor xenograft with a 177lutetium-labeled immunoconjugate. Schlom, J., Siler, K., Milenic, DE., et al.[2013]

The study successfully optimized the formulation of [177Lu]Lu-DOTA-Exendin-4, achieving over 95% radiolabeling yield, which is crucial for effective radiotherapy of insulinomas.

In vivo studies in mice demonstrated that [177Lu]Lu-DOTA-Exendin-4 specifically targets GLP-1 receptors, with significant accumulation in the pancreas and kidneys, indicating its potential efficacy and stability for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation of [177Lu]Lu-DOTA-Ahx-Lys40-Exendin-4 for radiotherapy of insulinoma: a detailed insight into the radiochemical intricacies. Guleria, M., Das, T., Amirdhanayagam, J., et al.[2020]

In a study of 52 patients undergoing Lu-177-PSMA-617 radioligand therapy for metastatic castration-resistant prostate cancer, the median overall survival was found to be 55.6 weeks, highlighting the treatment's potential efficacy.

Key predictors of overall survival included lower pre-therapeutic hemoglobin levels and higher lactate dehydrogenase (LDH) levels, as well as the presence of hepatic metastasis, indicating that these factors can help guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy. Wrenger, R., Jüptner, M., Marx, M., et al.[2022]

In a study of 52 patients with advanced pancreatic neuroendocrine tumors, (177)Lu-DOTATATE therapy demonstrated significant antitumor activity, achieving an overall disease control rate of 81% with both full and reduced dosages.

Patients receiving the higher dosage of 27.8 GBq had a longer progression-free survival compared to those on the reduced dosage of 18.5 GBq, suggesting that the higher dose is more effective and is recommended for eligible patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with the radiolabelled somatostatin analog Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. Sansovini, M., Severi, S., Ambrosetti, A., et al.[2022]

[177Lu]Lu-PSMA-617 is effective in targeting prostate cancer, but some patients do not respond well; ongoing research is exploring combination therapies to improve outcomes for both treatment-naïve and resistant patients.

Combining [177Lu]Lu-PSMA-617 with other treatments, such as alpha radiation emitters and immune checkpoint inhibitors, shows promise in enhancing therapeutic responses, particularly for patients who have developed resistance to initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. Arbuznikova, D., Eder, M., Grosu, AL., et al.[2023]

Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is a safe and effective treatment for patients with inoperable or metastatic neuroendocrine neoplasia (NEN), showing a clinical response of regressive disease in 47.6% of cases.

The study found no severe renal or hematological toxicity in 30 patients treated with Lu-DOTATATE, suggesting that while hematological parameters may influence survival, the treatment itself is well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. Löser, A., Schwarzenböck, SM., Heuschkel, M., et al.[2018]

The PROQURE-I study is investigating the safety and efficacy of combining standard external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) with a single dose of [177Lu]Lu-PSMA-617 in treating prostate cancer patients with locoregional lymph node disease (N1M0), aiming to improve outcomes for this challenging patient group.

This is the first prospective study to explore this combination in treatment-naïve men, with a focus on determining the maximum tolerated dose of [177Lu]Lu-PSMA-617 and assessing its tolerability and preliminary efficacy, suggesting a potential for enhanced anti-tumor effects with limited toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of concurrent external beam radiotherapy and [177Lu]Lu-PSMA-617 for node-positive prostate cancer in treatment naïve patients, phase I study (PROQURE-I trial). van der Sar, ECA., Braat, AJAT., van der Voort-van Zyp, JRN., et al.[2023]

The study developed a new radiopharmaceutical by labeling trastuzumab with (177)Lu, which demonstrated high radiochemical purity (91%) and stability in both PBS buffer and blood serum for up to 96 hours.

Trastuzumab-(177)Lu showed significantly increased cytotoxicity, with a five-fold increase in toxicity against HER2-positive SKBr3 breast cancer cells compared to unlabeled trastuzumab, indicating its potential as an effective treatment for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of trastuzumab labeled 177Lu on MCF7 and SKBr3 cell lines. Rasaneh, S., Rajabi, H., Hossein Babaei, M., et al.[2015]

A study analyzing 4,339 adverse events (AEs) associated with radium-223 from the Eudra-Vigilance database found that the most common AEs were hematological, general, and gastrointestinal disorders, with over 90% classified as serious and 8% fatal.

Older patients (over 85 years) treated with radium-223 showed a higher risk of cardiac, infectious, and metabolic disorders compared to younger patients, indicating the need for careful monitoring in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database. Tema, G., Lombardo, R., Voglino, O., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

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

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10828073/

The Balance Between the Therapeutic Efficacy and Safety ...

Treatment of PC-3 tumors with all three studied [177Lu]Lu-NeoB doses was effective. Median survival times were significantly (p < 0.0001) ...

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spandidos-publications.com

spandidos-publications.com/10.3892/etm.2024.12514

Current clinical application of lutetium‑177 in solid tumors ...

In 2015, internal radiation therapy using 177Lu-PSMA-I&T was reported to be effective and safe in two patients with metastatic prostate cancer, ...

4.

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 ...

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clinicaltrials.eu

clinicaltrials.eu/inn/neob/

Neob – Application in Therapy and Current Clinical Research

NEOB: A Promising New Drug for Cancer Treatment. NeoB is an investigational drug being studied in clinical trials for various advanced solid tumors.

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aacrjournals.org

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We aim to characterize the safety, tolerability, whole-body distribution, radiation dosimetry and antitumor activity of 177 Lu-NeoB in patients with selected ...

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link.springer.com

link.springer.com/article/10.1007/s11307-023-01851-4

The Balance Between the Therapeutic Efficacy and Safety ...

Treatment of PC-3 tumors with all three studied [177Lu]Lu-NeoB doses was effective. Median survival times were significantly (p < 0.0001) ...