Targeted Radionuclide Therapy for Non-Small Cell Lung Cancer

Overseen By Julie L Sutcliffe, Phd

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Davis

Disqualifiers: Congestive heart failure, Active infection, others

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

Compensation: Varies

Number of Visits: 5

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for non-small cell lung cancer (NSCLC) that has spread to other parts of the body. The study aims to determine if [177Lu]Lu DOTA-ABM-5G, a targeted radionuclide therapy, is safe and effective by using a special scan to assess its ability to target cancer spots. Individuals with NSCLC that has worsened after at least one other treatment and have noticeable cancer spots on scans might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new therapy.

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

The trial requires that you stop any prior systemic therapy at least 2 weeks before the PET scan, which is a washout period (time without taking certain medications).

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

Research shows that a new treatment pair, [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G, is being tested for safety in people with non-small cell lung cancer. These treatments have shown promise in diagnosing and treating cancer. Early results suggest that patients might manage the side effects.

This is an early-phase study, meaning the treatments are being tested in humans for the first time to assess safety. Although the main focus is on safety, there is still limited information about how people will react to the treatments. This trial will help researchers learn more about any side effects and how well patients tolerate the treatment.

In the past, Lutetium-177, a component of [177Lu]Lu DOTA-ABM-5G, has been used safely for other cancers like prostate and stomach cancer. While this provides some confidence about its use, each new treatment can have different effects. Participating in the trial will help gather important data on safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for non-small cell lung cancer (NSCLC) include surgery, chemotherapy, radiation therapy, or targeted drugs that focus on specific proteins. However, [177Lu]Lu DOTA-ABM-5G works differently by using a targeted radionuclide therapy approach. It delivers radioactive particles directly to cancer cells, allowing for precise treatment with potentially fewer side effects on healthy tissues. Researchers are excited because this method could improve targeting of cancerous lesions, potentially leading to better outcomes for patients with advanced or hard-to-treat NSCLC.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that combining [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G might aid in diagnosing and treating advanced non-small cell lung cancer (NSCLC). In this trial, patients will undergo [68Ga]Ga DOTA-5G PET/CT scans to determine eligibility for [177Lu]Lu DOTA-ABM-5G therapy. Studies have found that treatments with Lutetium-177, a similar substance, successfully slow tumor growth in other cancers. Early results suggest that this dual approach, diagnosing and treating cancer, could be safe and manageable for patients. The [177Lu]Lu DOTA-ABM-5G specifically targets cancer cells, potentially shrinking tumors. While these initial findings are promising, further research is needed to confirm its effectiveness for NSCLC. ^{2 3 4 5 6}

Who Is on the Research Team?

Julie Sutcliffe

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for patients with advanced non-small cell lung cancer that has spread to other parts of the body. Participants should be adults who have tried previous treatments without success and are now looking for new options.

Inclusion Criteria

I have available tumor tissue samples from previous tests.

I can take care of myself but might not be able to do heavy physical work.

Completion of entry into [68Ga]Ga DOTA-5G PET study and completion of scan

Exclusion Criteria

INR >2.0: PTT>15 seconds above ULN

Pregnant or lactating women

Psychiatric illness/social situations that would interfere with compliance with study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Imaging and Stratification

Participants undergo [68Ga]Ga DOTA-5G PET/CT scans to confirm eligibility for the [177Lu]Lu DOTA-ABM-5G therapy

2 hours

1 visit (in-person)

Treatment

Participants receive a single dose of [177Lu]Lu DOTA-ABM-5G therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• [177Lu]Lu DOTA-ABM-5G
• [68Ga]Ga DOTA-5G

Trial Overview The study is testing two related drugs, [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G, to see if they're safe and effective in treating metastatic lung cancer. It's an early-phase trial, meaning it's one of the first times these drugs are being given to people.

How Is the Trial Designed?

Group I: [177Lu]Lu DOTA-ABM-5G single dose therapy study Experimental Treatment 1 Intervention

Patients will be undergo \[68Ga\]Ga DOTA-5G PET/CT scans to confirm eligibility for the \[177Lu\]Lu DOTA-ABM-5G therapy. Patients with sufficient lesion uptake of \[68Ga\]Ga DOTA-5G PET/CT will be offered therapy.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

The study successfully converted a gallium-68 imaging agent into a lutetium-177 therapeutic agent for prostate cancer, demonstrating strong PSMA binding affinity comparable to the FDA-approved [177Lu]Lu-PSMA-617.

Biodistribution studies in mice showed that the new agent [177Lu]Lu-7 had a longer blood half-life and higher tumor uptake than both [177Lu]Lu-4 and [177Lu]Lu-PSMA-617, indicating its potential for improved therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). Zha, Z., Choi, SR., Li, L., et al.[2022]

177Lu-DOTA-Peptide 2, a new radioantagonist, showed high stability and selective binding to somatostatin receptors in HT-29 colorectal cancer cells, indicating its potential for targeted therapy.

The study demonstrated that 177Lu-DOTA-Peptide 2 has a low internalization rate and a high tumor uptake, making it a promising candidate for radionuclide therapy in treating somatostatin receptor-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. Behnammanesh, H., Erfani, M., Hajiramezanali, M., et al.[2023]

In a study of 84 Asian patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Lutetium-177 PSMA radioligand therapy, the median overall survival was 12.2 months and the median PSA progression-free survival was 5.2 months, indicating promising efficacy.

A significant 51.8% of patients experienced a PSA decline of 50% or more, which was linked to longer overall survival and PSA progression-free survival, while the treatment showed a manageable safety profile with grade 3 hematotoxicity occurring in 13 out of 78 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study). Chua, WM., Lam, WW., Tong, AK., et al.[2023]

Lutetium-177 labeled radiopharmaceuticals, specifically 177Lu-EDTMP and 177Lu-DOTA-TATE, have shown promising efficacy in treating bone pain from metastatic cancer and neuroendocrine tumors, with no serious adverse effects reported even in patients with renal disease.

In a study involving 13 patients, 177Lu-EDTMP demonstrated high and rapid uptake in bone metastases, while 177Lu-DOTA-TATE resulted in partial remissions in 4 out of 5 patients, indicating effective therapeutic responses without significant renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay. Balter, H., Victoria, T., Mariella, T., et al.[2019]

In a study of 75 patients with metastatic prostate cancer, 6 were excluded from Lutetium-177 [177Lu]-PSMA-617 treatment due to PSMA-negative/FDG-positive discordance, but 89 suitable targets for biology-guided radiotherapy (BgRT) were identified.

The research suggests that combining BgRT with Lutetium-177 [177Lu]-PSMA-617 is feasible for treating patients with discordant metastases, particularly highlighting that bone and lung metastases are the most suitable candidates for this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. Gaudreault, M., Chang, D., Hardcastle, N., et al.[2023]

In a study of 40 patients with bone pain from skeletal metastases, [177Lu]Lu-DOTA-ZOL demonstrated a high overall response rate of 90%, with significant improvements in pain scores and performance status over a median follow-up of 10 months.

The treatment was well-tolerated, with no patients experiencing severe toxicity (grade III/IV) related to blood, kidney, or liver function, indicating a favorable safety profile for this radiopharmaceutical in managing cancer-related bone pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results. Yadav, MP., Ballal, S., Meckel, M., et al.[2020]

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]

177Lu is a promising radionuclide for targeted therapy due to its high purity and suitable decay characteristics, produced with 99.99% radionuclidic purity and moderate specific activity.

The study successfully created a novel estradiol-DOTA conjugate for radiolabelling with 177Lu, which showed potential biological activity in vitro with MCF-7 breast cancer cells that express estrogen receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An estradiol-conjugate for radiolabelling with 177Lu: an attempt to prepare a radiotherapeutic agent. Banerjee, S., Das, T., Chakraborty, S., et al.[2013]

Citations

1. cancer.gov cancer.gov/clinicaltrials/NCI-2024-00931

A Pair of Radioactive Drugs for Diagnosing and Treating ... [68Ga] Ga DOTA-5G and [177Lu] Lu DOTA-ABM-5G may be an effective combination for diagnosing and treating patients with metastatic non-small cell lung cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06228482

Molecularly Targeted Radionuclide Therapy Via the ... This is a Phase I study to evaluate the safety and efficacy of the [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G theranostics pair in patients with metastatic ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03571

A Theranostic Approach ([68Ga]Ga DOTA-5G and [177Lu] ... A theranostic approach with [68Ga]Ga DOTA-5G and [177]Lu DOTA-ABM-5G may be safe, tolerable and/or effective in detecting and treating metastatic cancer.

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

Current clinical application of lutetium‑177 in solid tumors ... The results suggest that 177Lu-DOTA-TATE can control tumor growth (52). Metastatic salivary gland cancer and 177Lu-PSMA-617. PSMA is expressed on tumor cells or ...

5. withpower.com withpower.com/trial/phase-1-carcinoma-non-small-cell-lung-2024-c24c9

Targeted Radionuclide Therapy for Non-Small Cell Lung Cancer What data supports the effectiveness of the treatment [177Lu]Lu DOTA-ABM-5G for non-small cell lung cancer? Research on similar treatments using Lutetium-177, ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/p1300

First-in-human study of the theranostic pair [68Ga]Ga DOTA ... This is a Phase I, first-in-human study to evaluate the safety of the radiotheranostic peptide pair, [ 68 Ga]Ga DOTA-5G and [ 177 Lu]Lu DOTA-ABM-5G in patients ...