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

Trial Summary

What is the purpose of this trial?

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 non small cell lung cancer (NSCLC).

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).

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, like [177Lu]Lu-PSMA-617 for prostate cancer and 177Lu-DOTA-TATE for neuroendocrine tumors, shows that Lutetium-177 can effectively target and treat tumors by delivering radiation directly to cancer cells, leading to tumor uptake and potential remission without significant side effects. ^{1 2 3 4 5}

Is there any safety data available for targeted radionuclide therapy using Lutetium-177 in humans?

The study on [177Lu]Lu-DOTA-ZOL for bone pain relief in patients with cancer that has spread to the bones provides some safety data, indicating it has been evaluated for safety in humans. ^{1 3 4 5 6}

What makes the drug [177Lu]Lu DOTA-ABM-5G, [68Ga]Ga DOTA-5G unique for treating non-small cell lung cancer?

This drug is unique because it combines diagnostic and therapeutic capabilities by using two different isotopes: gallium-68 for imaging and lutetium-177 for targeted radionuclide therapy, allowing for precise targeting and treatment of cancer cells. ^{1 2 5 7 8}

Research Team

Julie Sutcliffe

Principal Investigator

University of California, Davis

Eligibility Criteria

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.

My lung cancer has spread and can be measured by scans.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

References

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

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). [2022]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay. [2019]

3. Iran pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. [2023]

6. Australia pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study). [2023]

7. England pubmed.ncbi.nlm.nih.gov

An estradiol-conjugate for radiolabelling with 177Lu: an attempt to prepare a radiotherapeutic agent. [2013]

8. Iran pubmed.ncbi.nlm.nih.gov

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