GD2-SADA:177Lu-DOTA Complex for Small Cell Lung Cancer

Recruiting at 7 trial locations

Overseen By Joris Wilms

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Y-mAbs Therapeutics

Must not be taking: Investigational therapies

Disqualifiers: Autoimmune diseases, HIV, Hepatitis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for certain cancers using a two-part method. The first part finds and attaches to cancer cells, and the second part delivers radiation to kill them. It aims to see if this treatment is safe and can be tolerated by patients with Small Cell Lung Cancer, Sarcoma, and Malignant Melanoma.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic chemotherapy, radiotherapy, immunotherapy, or major surgery at least 3 weeks before starting the study treatment. It does not specify about other medications, so you should discuss your current medications with the trial team.

Is the GD2-SADA:177Lu-DOTA Complex safe for humans?

Research on a similar treatment, 177Lu-DOTATATE, shows it is generally safe for treating certain types of tumors, with most side effects being reversible. Common side effects include low white blood cell counts, but serious long-term effects like leukemia are rare. ^{1 2 3 4 5}

What makes the GD2-SADA:177Lu-DOTA Complex treatment unique for small cell lung cancer?

The GD2-SADA:177Lu-DOTA Complex is unique because it combines a targeting molecule (GD2-SADA) with a radioactive component (177Lu-DOTA) to specifically target and treat cancer cells, potentially offering a more precise treatment option compared to traditional chemotherapy. This approach is similar to other radionuclide therapies like 177Lu-DOTATATE, which have shown effectiveness in treating neuroendocrine tumors by targeting specific receptors on cancer cells. ^{1 3 6 7 8}

Research Team

Taofeek K Owonikoko, MD/PhD

Principal Investigator

University of Maryland, Marlene & Steward Greenebaum Comprehensive Cancer Center 22 S Greene St, Baltimore, MD 21201

Eligibility Criteria

This trial is for adults with Small Cell Lung Cancer, Sarcoma, or Malignant Melanoma. Participants must have a life expectancy over 3 months, certain blood cell counts within range, measurable disease by RECIST 1.1 standards, and good performance status. They should not have had recent cancer treatments or suffer from autoimmune diseases.

Inclusion Criteria

You are expected to live for more than 3 months.

My kidney function is good based on my creatinine levels.

Signed informed consent from patient, legal guardian(s) and/or adolescents obtained in accordance with local regulations. Pediatric patients must provide assent as required by local regulations.

Exclusion Criteria

I have been treated with anti-GD2 antibody before.

I haven't had chemotherapy, radiotherapy, immunotherapy, or major surgery in the last 3 weeks.

I have an autoimmune disease, immunodeficiency, or an active infection with HIV or hepatitis B/C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

GD2-SADA Dose Escalation

Part A: GD2-SADA dose escalation phase, patients receive one treatment cycle

6 weeks

177Lu-DOTA Dose Escalation

Part B: 177Lu-DOTA dose escalation phase, patients receive up to 2 treatment cycles

6 weeks

Repeated Dosing

Part C: Repeated dosing phase with doses determined in Part A and B, up to 5 cycles

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GD2-SADA:177Lu-DOTA Complex (Radioimmunotherapy)

Trial Overview The trial tests GD2-SADA:177Lu-DOTA Complex on patients to evaluate its safety and how well they tolerate it. It's a two-step radioimmunotherapy involving separate administrations of GD2-SADA and 177Lu-DOTA.

Participant Groups

Group I: GD2-SADA:177Lu-DOTA Complex Experimental Treatment 1 Intervention

GD2-SADA IV. infusion followed by 177Lu-DOTA IV. infusion (The IMP is a two-step radioimmunotherapy, delivered as two separate products GD2-SADA and 177Lu-DOTA ). 1 treatment cycle in Part A, 2 treatment cycles in Part B and up to 5 treatment cycles in Part C

Who Is Running the Clinical Trial?

Y-mAbs Therapeutics

Lead Sponsor

Trials

26

Recruited

1,600+

Findings from Research

In a study of 48 patients with advanced progressive lung neuroendocrine tumors, treatment with 177Lu-DOTATATE showed a median progression-free survival of 23 months and an overall survival of 59 months, indicating its efficacy in managing these tumors.

The treatment was found to be safe, with most adverse events being reversible; the most common severe side effect was lymphopenia, occurring in 14% of patients, and there were no cases of myelodysplasia or leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of 177Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study. Zidan, L., Iravani, A., Oleinikov, K., et al.[2022]

The co-infusion of amino acids (AA) during treatment with 177Lu-Dotatate significantly affects its pharmacokinetics, increasing the elimination rate constant by an average of 1.5-fold, which helps reduce potential nephrotoxicity.

However, this effect varies greatly among individuals, leading to high inter-individual variability in drug exposure and associated hematological toxicity, such as lymphopenia, indicating the need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Interaction of Amino Acid Infusion on 177Lu-Dotatate Pharmacokinetics in Patients with Gastroenteropancreatic Neuroendocrine Tumors. Puszkiel, A., Bauriaud-Mallet, M., Bourgeois, R., et al.[2020]

Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE has shown a 39% objective response rate and a 43% rate of stable disease in over 1,200 patients with neuroendocrine tumors, indicating its efficacy in treating these slow-growing tumors.

The therapy is considered safe, with only a small percentage of patients experiencing long-term toxicities, such as acute leukemia (0.7%) and myelodysplastic syndrome (1.5%), while no significant renal or hepatic failures were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. Brabander, T., van der Zwan, WA., Teunissen, JJM., et al.[2022]

The targeted alpha-particle therapy [225Ac]Ac-DOTA-TATE showed promising efficacy in delaying tumor growth in small animal models of lung neuroendocrine neoplasms, indicating its potential for treating patients who are resistant to standard therapies like [177Lu]Lu-DOTA-TATE.

In toxicity studies, [225Ac]Ac-DOTA-TATE demonstrated a high safety profile with no significant adverse effects in most animals, although higher doses led to chronic nephropathy, highlighting the need for careful dosing in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of [225Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms. Tafreshi, NK., Pandya, DN., Tichacek, CJ., et al.[2022]

Salvage treatment with [177Lu-DOTA,Tyr3]octreotate is effective and safe for patients with progressive bronchial neuroendocrine tumors (NET) or gastroenteropancreatic NET (GEP-NET), showing a median overall survival of 80.8 months after initial treatment.

The treatment resulted in low rates of severe side effects, with only 6.6% and 7.7% of patients experiencing grade III/IV bone marrow toxicity after re-treatment and re-re-treatment, respectively, and no cases of severe kidney toxicity were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. van der Zwan, WA., Brabander, T., Kam, BLR., et al.[2020]

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]Lu-DOTA-TATE shows promising antitumor activity in treating advanced somatostatin receptor-positive tumors, including pheochromocytoma/paraganglioma and bronchial neuroendocrine tumors, based on a systematic review of 16 studies.

The treatment is generally safe, with most side effects being mild to moderate and transient, similar to those observed in patients with gastroenteropancreatic neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review. Hertelendi, M., Belguenani, O., Cherfi, A., et al.[2023]

References

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

Efficacy and Safety of 177Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of the Interaction of Amino Acid Infusion on 177Lu-Dotatate Pharmacokinetics in Patients with Gastroenteropancreatic Neuroendocrine Tumors. [2020]

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

Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. [2022]

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

Preclinical evaluation of [225Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE in older patients with metastatic neuroendocrine tumours: safety, efficacy and health-related quality of life. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. [2020]

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

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review. [2023]